CTRI/2026/01/102063 [Registered on: 27/01/2026] Trial Registered Prospectively
Last Modified On:
27/07/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
The purpose of this study is to evaluate the safety, tolerability, and drug levels of BMS-986454 in participants with Rheumatoid Arthritis
Scientific Title of Study
A 2-Part, Phase 1b Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Pharmacodynamics of BMS-986454 in Participants with Rheumatoid Arthritis
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
NCT07171983
ClinicalTrials.gov
U1111-1284-3324
UTN
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Manish Nagpal
Designation
Director
Affiliation
Bristol-Myers Squibb Company
Address
Bristol Myers Squibb
IT Park, Capital Land, 7th Floor, Madhapur
Hyderabad, India -500081
Hyderabad TELANGANA 500081 India
Phone
919205140125
Fax
Email
Manish.Nagpal@bms.com
Details of Contact Person Scientific Query
Name
Manish Nagpal
Designation
Director
Affiliation
Bristol-Myers Squibb Company
Address
Bristol Myers Squibb
IT Park, Capital Land, 7th Floor, Madhapur
Hyderabad, India -500081
Hyderabad TELANGANA 500081 India
Phone
919205140125
Fax
Email
Manish.Nagpal@bms.com
Details of Contact Person Public Query
Name
Ahmed Riyaz
Designation
Global Trail Manager
Affiliation
Bristol Myers Squibb
Address
Bristol Myers Squibb
IT Park, Capital Land, 7th Floor, Madhapur
Hyderabad, India -500081
Hyderabad TELANGANA 500081 India
Phone
9160729292
Fax
Email
Riyaz.Ahmed2@bms.com
Source of Monetary or Material Support
Syngene International Limited
Plot No 2, 3 & 4, IV Phase
Bommasandra, Bangalore – 560099 Karnataka
Primary Sponsor
Name
Bristol-Myers Squibb Company
Address
3401 Princeton Pike,
Lawrenceville, NJ 08648
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
BristolMyers Squibb India Pvt Ltd
One International Centre, 6th Floor, Tower 1,
Senapati Bapat Marg, Elphistone (W), Mumbai- 400013
India
Apollo Hospitals International Ltd Ethics Committee
Approved
Institutional Ethics Committee
Approved
Institutional Ethics Committee
Submittted/Under Review
INSTITUTIONAL ETHICS COMMITTEE
Approved
KIMS Ethics Committee
Submittted/Under Review
Lifepoint Research- Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: M060||Rheumatoid arthritis without rheumatoid factor,
Intervention / Comparator Agent
Type
Name
Details
Intervention
BMS 986454
BMS-986454
Administered as a subcutaneous (SC) injection
Part A: 300 mg once weekly for 4 weeks
Part B: Dose (less than or equal to 400 mg, determined after Part A) once every 28 days for 3 doses
Comparator Agent
Placebo matching BMS 986454
Dummy drug given in same manner as Intervention
Inclusion Criteria
Age From
18.00 Day(s)
Age To
65.00 Year(s)
Gender
Both
Details
6.1 Inclusion Criteria
Participants are eligible to be included in the study only if all the following criteria are met:
6.1.1 Inclusion Criteria for Part A
Signed Written Informed Consent
1) Participants must have signed and dated an IRB/IEC-approved written ICF in accordance with regulatory, local, and institutional guidelines. The study specific ICF and any optional ICFs (if applicable) must be obtained before performing any protocol-related procedures that are not part of normal patient care.
2) Participant is willing and able to adhere to the study visit schedule and other protocol requirements.
Note: Participants must agree to comply with the requirements and restrictions listed in the informed consent (IC) and in this protocol.
Type of Participant and Target Disease Characteristics
3) Male or female participants who meet 2010 ACR or EULAR classification criteria for RA45 (qualifying criteria must be documented at screening) and positive for anti-CCP or other ACPA antibodies.
Note: Rheumatoid factor positivity is not a requirement.
4) The participant’s RA must have onset after age 18 (ie, juvenile RA/juvenile idiopathic arthritis participants are excluded).
5) Disease onset must have been less than 2 years before screening.
6) For Part A, participants meeting 2010 ACR or EULAR classification criteria for RA must have either mild or moderate disease activity according to the DAS28-CRP scoring system at screening, and must remain in the same category of disease activity or better at Day -1.
Age of Participant
7) Participant must be 18 to 65 years of age, inclusive, at the time of signing the ICF.
Reproductive Status
Note: The investigator or designee shall counsel IOCBP participants (as defined in APPENDIX 3) and male (as assigned at birth) participants who are sexually active with IOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy.
Note: The investigator or designee shall evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
Note: Local laws and regulations may require the use of alternative and/or additional contraceptive methods.
8) Female (as assigned at birth) participants:
Note: Female (as assigned at birth) participants who are not of childbearing potential (as defined in Appendix 3) must have documented proof of reproductive status. Documentation can be obtained from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview. Individuals who are not of childbearing potential are exempt from contraceptive requirements.
a) IOCBP must have a negative highly sensitive urine or serum as required by local regulations pregnancy test (minimum sensitivity 25 IU per L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study intervention.
Note: If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
Note: The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to potentially decrease the risk for inclusion of an individual with an undetected pregnancy.
b) IOCBP and male (as assigned at birth) participants who are sexually active with IOCBP must agree to follow instructions for method(s) of contraception as described below and included in the ICF.
Note: IOCBP are permitted to use hormonal contraceptive methods (as described in APPENDIX 3).
c) A female (as assigned at birth) is eligible to participate if they are not pregnant or breastfeeding and at least 1 of the following conditions applies:
(1) Is not an IOCBP
OR
(2) Is an IOCBP and using a contraceptive method that is highly effective (with a failure rate of less than 1 percentage per year), preferably with user independent methods, as described in APPENDIX 3, during the intervention period and for at least 120 days after last dose and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction for the same period.
Note: Azoospermic males are exempt from contraceptive requirements.
Note: Male (as assigned at birth) participants should maintain their usual practice regarding contraception (if any); however, no specific or additional contraceptive measures are required.
Note: Male (as assigned at birth) participants receiving monoclonal antibodies as monotherapy will not be required to use contraceptive measures or a latex or other synthetic condom during sexual activity with an IOCBP partner. Information regarding pregnancies in IOCBP partners of male (as assigned at birth) participants should not be collected for studies in which there are no contraception requirements for male (as assigned at birth) participants.
6.1.2 Inclusion Criteria for Part B
Participants are eligible to be included in the study only if all the following criteria are met: Signed Written Informed Consent
1) Participants must have signed and dated an IRB or IEC-approved written ICF in accordance with regulatory, local, and institutional guidelines. The study specific ICF and any optional ICFs (if applicable) must be obtained before performing any protocol-related procedures that are not part of normal patient care.
2) Participant is willing and able to adhere to the study visit schedule and other protocol requirements.
Note: Participants must agree to comply with the requirements and restrictions listed in the ICF and in this protocol.
Type of Participant and Target Disease Characteristics
3) Male or female participants who meet 2010 ACR or EULAR classification criteria for RA45 (qualifying criteria must be documented at screening) and positive for anti-CCP or other ACPA antibodies.
Note: Rheumatoid factor positivity is not a requirement.
4) The participant’s RA must have onset after age 18 (ie, juvenile RA/juvenile idiopathic arthritis participants are excluded).
5) Disease onset must have been less than 2 years before screening.
6) MTX-incomplete responder (IR) with mild or moderate disease activity according to the DAS28-CRP scoring system at screening, and must remain in the same category of disease activity or better (ie, not in severe disease activity) at Day -1.
7) MTX requirements for incomplete responders are as follows:
a) Participants must have been taking MTX for at least 3 months at a minimal weekly dose of 15 mg (maximum 25 mg or week) and at a stable dose and administration route for at least 4 weeks before randomization. A lower dose of MTX is permitted if documented that a dose of 15 mg weekly was not possible due to toxicity or intolerance and the dose is at least 10 mg MTX at the screening visit.
b) Participants using IM or SC MTX for administration of their weekly dose are eligible.
8) Evidence of swelling in at least 1 joint of the hand or wrist by clinical examination at screening
and Day -1.
9) hsCRP above the upper range of normal for the laboratory where the testing is done at the screening visit. These may be retested 1 time during screening period, if initial screening results are not within inclusion level.
Age of Participant
10) Participant must be 18 to 65 years of age inclusive at the time of signing the ICF.
Reproductive Status
Note: The investigator or designee shall counsel IOCBP participants (as defined in APPENDIX 3) and male (as assigned at birth) participants who are sexually active with IOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy.
Note: The investigator or designee shall evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
Note: Local laws and regulations may require the use of alternative and/or additional contraceptive methods.
11) Female (as assigned at birth) participants:
Note: Female (as assigned at birth) participants who are not of childbearing potential (as defined in APPENDIX 3) must have documented proof of reproductive status. Documentation can be obtained from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview. Individuals who are not of childbearing potential are exempt from contraceptive requirements.
a) IOCBP must have a negative highly sensitive urine or serum as required by local regulations pregnancy test (minimum sensitivity 25 IU per L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study intervention.
Note: If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
Note: The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to potentially decrease the risk for inclusion of an individual with an undetected pregnancy.
b) IOCBP and male (as assigned at birth) participants who are sexually active with IOCBP must agree to follow instructions for method(s) of contraception as described below and included in the ICF.
Note: IOCBP are permitted to use hormonal contraceptive methods (as described in APPENDIX 3).
c) A female (as assigned at birth) is eligible to participate if they are not pregnant or breastfeeding and at least 1 of the following conditions applies:
(1) Is not an IOCBP
OR
(2) Is an IOCBP and using a contraceptive method that is highly effective (with a failure rate of less than 1 percentage per year), preferably with user independent methods, as described in APPENDIX 3, during the intervention period and for at least 120 days after last dose and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction for the same period.
Note: Azoospermic males are exempt from contraceptive requirements.
Note: Male (as assigned at birth) participants should maintain their usual practice regarding contraception (if any); however, no specific or additional contraceptive measures are required.
Note: Male (as assigned at birth) participants receiving monoclonal antibodies as monotherapy will not be required to use contraceptive measures or a latex or other synthetic condom during sexual activity with an IOCBP partner. Information regarding pregnancies in IOCBP partners of male (as assigned at birth) participants should not be collected for studies in which there are no contraception requirements for male (as assigned at birth) participants.
ExclusionCriteria
Details
6.2 Exclusion Criteria
Participants are excluded from the study if any of the following criteria are met:
6.2.1 Exclusion Criteria for Part A
Medical Conditions
1) With the exception of RA, any significant medical condition (including but not limited to, neurological, GI, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or other major disorders) that, in the Investigator’s judgment, will substantially increase the risk to the participant if he or she participates in the study.
2) Participants without CCP or ACPA positivity.
Note: Given the use of citrullinated targets to determine the pharmacodynamic range and the recommended dose for further studies, evidence of citrullination via CCP/ACPA positivity is required for this first study in participants with RA.
3) Participant with severe RA as assessed by DAS28-CRP at screening or Day -1.
4) Participants with concomitant other rheumatologic/autoimmune conditions are excluded with the exception of: osteoarthritis, fibromyalgia, autoimmune thyroid disease, or secondary Sjogren syndrome provided they do not meet other exclusion criteria.
5) Participants with RA and concomitant Felty syndrome, RA-associated interstitial lung disease with functional limitation or requiring additional medication specifically to treat the interstitial lung disease, or active rheumatoid vasculitis.
6) Participant has any condition aside from RA that confounds the ability to interpret data from the study.
7) Participant has any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if the participant was to participate in the study.
8) Participant has an active acute or uncontrolled chronic systemic fungal, bacterial (including Mycobacterium tuberculosis [TB]), and or viral infection within 30 days prior to first dosing. 9) Any major surgery within 4 weeks prior to first study intervention administration or before
4 weeks have passed from the time of the last planned PK blood collection.
Reproductive Status
10) Women who are pregnant or breastfeeding.
Prior/Concomitant Therapy
11) Inability to comply with restrictions and prohibited treatments as listed in Section 7.7: Prior and Concomitant Therapy.
12) Participant was exposed to an investigational drug (new chemical entity) within 30 days preceding the first dose administration, or 5 half-lives of that investigational drug, if known (whichever is longer).
13) Exclusions related to therapies for RA:
a) Participant has used any biologic or targeted-synthetic DMARD within 30 days prior to the first dose administration, or 5 half-lives of that drug, if known (whichever is longer). This includes medications such as but not limited to: IV immunoglobulin (IVIg), anti-TNF biologics, B cell depleting biologics, abatacept, JAK inhibitors, anti-IL1 biologics, or anti-IL6-R biologics. If there are questions, please, contact the Sponsor’s Clinical Trial Physician.
b) Participant has had or is planned to have intraarticular glucocorticoid injection within 3 months of Day -1 given the data on the effect of intraarticular glucocorticoid injection on citrullination.44
i) If the participant has a flare of disease activity prior to Day -1 that requires intraarticular glucocorticoid injection, the flare would constitute screen failure per inclusion and exclusion criteria because of a worsening in disease activity requiring a change in therapeutic management.
c) Oral glucocorticoid use is permitted, but the dose must be less than or equal to 10 mg/day prednisone or equivalent and stable for greater than 1 month before screening and the participant must be thought by his or her treating rheumatologist to be able to keep the dose level stable throughout the study intervention dosing period of this study. Further specifications on steroid use are as follows:
i) Topical and inhaled steroid use is permitted but must follow a stable regimen throughout the study and cannot be used on an as-needed basis.
ii) Inhaled steroid for non-RA conditions will not count against the maximum daily glucocorticoid dose.
iii) Intramuscular glucocorticoid administration cannot occur during the screening period and is prohibited during the 4-week treatment period unless needed to urgently treat a flare of disease activity.
iv) IV glucocorticoid administration is prohibited less than 4 weeks prior to Day 1.
d) Participant is currently using anti-malarials, eg, hydroxychloroquine, chloroquine, or quinacrine or has used hydroxychloroquine, chloroquine, or quinacrine within the 30 days preceding the first dose administration given the data that hydroxychloroquine and chloroquine have effects on PAD4 and citrullination.6,46
i) This includes use of anti-malarials as part of “triple therapy” (ie, methotrexate, sulfasalazine, hydroxychloroquine [or analog]).
e) Conventional DMARDs, such as methotrexate, leflunomide, and sulfasalazine, are allowable during the study.
i) Conventional DMARDs must be at a stable dose for at least 8 weeks prior to Day 1, and the participant must be felt by his/her treating rheumatologist to have a reasonably high chance of remaining at that stable dose for the duration of the dosing period (ie, the treating rheumatologist was not planning to increase the dose of DMARD in the timeframe that would overlap with the study intervention dosing period). Subcutaneous methotrexate is allowable if the participant is willing to avoid injection at sites that are used for the study drug and can inject the methotrexate on a day when he/she is not being dosed with study intervention. Recording of injection-site reactions for participants on subcutaneous methotrexate must clearly indicate whether the injection site was used for methotrexate or study intervention.
f) Oral or topical non-steroidal anti-inflammatory drugs are also allowable during the study.
Other exceptions to prior/concomitant may apply on a case-by-case basis if considered not to interfere with the study objectives as agreed to by the investigator and CRO Medical Monitor. The investigator should discuss concomitant medications that cannot beheld from the time of signing the ICF to the last PK collection timepoint.
14) Participant has used any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days prior to the first dose administration. Exceptions may apply on a case-by-case basis if considered not to interfere with the study objectives as agreed to by the investigator and CRO Medical Monitor.
15) Vaccination or plans for vaccination with any live or live attenuated vaccine within 30 days before screening, during the course of the study, or within 120 days after the last dose of study intervention.
16) Vaccination or plans for vaccination with non-live vaccines within 30 days before Day -1 until the last outpatient clinical site visit.
Physical and Laboratory Test Findings
17) With the exception of findings that are expected in a participant with mild or moderate RA in the clinical experience of the investigator or participant’s treating rheumatologist with the individual participant, participants with RA are excluded if they exhibit evidence of organ dysfunction or any clinically significant deviation from the institution’s reference range or the participant’s historical trend over the past 6 months prior to screening in physical examination, vital signs, 12-lead ECG, or clinical laboratory tests.
Note: Mild or moderate disease activity status for RA is defined according to DAS28-CRP obtained at screening.
Note: Any participant that develops an exacerbation/flare of disease activity that requires a change in baseline RA treatment dosing prior to Day -1 should be considered a screen failure, but he/she may be re-screened at a later data if meeting criteria for mild or moderate RA and again being on a stable dose level of allowable RA treatment for at least 8 weeks prior to the new planned Day -1.
18) Body mass index (BMI) is outside of the range: 18 and 32 kg/m2 inclusive at screening. BMI equal too weight (kg)/ [height (m)]2.
19) Participant is febrile.
20) Participant has supine systolic blood pressure (BP) less than or equal too 100 or greater than or equal too 140 mmHg, supine diastolic BP less than or equal too 50 or greater than or equal too 90 mmHg, and resting heart rate less than or equal too 40 or greater than or equal too 110 bpm at screening or Day -1.
21) Participant has abnormal or clinically significant 12-lead ECG, where the abnormal finding may impact the ability to interpret an AE. In addition:
a) If female, participant has a Fridericia’s corrected QT interval (QTcF) value greater than or equal too 450 msec at screening or Day -1.
b) If male, participant has a QTcF value greater than or equal too 430 msec at screening or Day -1.
22) Clinical laboratory safety test results at screening or Day -1 that are considered clinically significant by the investigator (including those within the reference range — for example, a tripling of serum creatinine from screening to Day -1, though all values remain within the reference range, may be reasonably considered clinically significant given the fold change between the 2 measurements).
Additionally, no clinical laboratory safety test result at screening or Day -1 should be in the range that constitutes a Grade 2 (moderate) or higher deviation from the reference range per the Rheumatology Common Toxicity Criteria v.2.1 (APPENDIX 4). While a single out-of-range laboratory test result may not be viewed as clinically significant, if it is related to other laboratory test results that, in totality, suggest an abnormal medical condition, then that should be factored into decision making on eligibility. For example, a hemoglobin of 12.4 gm/dL (lower limit of reference range 12.5 gm/dL) in a male may be viewed as not clinically significant. However, if the same participant also has a low mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCH), the totality of low hemoglobin and microcytosis and hypochromia would indicate anemia and the participant is ineligible.
23) Regardless of clinical significance or toxicity grading, any result that falls outside the range(s) specified below is exclusionary:
a) Absolute neutrophil count (ANC) must be above 1500 cells/mm3 but below the upper limit of the reference range for the laboratory where the study is conducted at screening and on Day -1.
b) Absolute lymphocyte count (ALC) must be above 1000 cells/mm3 but below the upper limit of the reference range for the laboratory where the study is conducted at screening and on Day -1.
c) Monocyte count must be within the reference range for the laboratory where the study is conducted at screening and on Day -1.
24) History of incompletely treated Mycobacterium tuberculosis (TB) infection, indicated by either:
a) Medical records documenting incomplete treatment for TB.
b) Participant’s self-reported history of incomplete treatment for TB.
Note: Participants with a history of TB who have undergone documented treatment accepted by the local health authorities may be eligible for study entry. The investigator must attest in the eCRF to reviewing documentation of the accepted TB treatment.
25) Participant has a positive QuantiFERON®-TB Gold (or equivalent) test result or 2 successive indeterminate QuantiFERON®-TB Gold (or equivalent) test results at screening.
26) Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, or human immunodeficiency virus (HIV)-1 and -2 antibody.
Note: Participants who received hepatitis B vaccination and who test positive for hepatitis B surface antibody and negative for both hepatitis B surface antigen and hepatitis B core antibody remain eligible for study participation.
27) Positive urine screen for drugs of abuse or positive or urine or breath alcohol test at screening and Day -1.
Note: Section 6.4.1 has additional guidance for the investigator on retesting laboratory parameters in participants during screening up to the day of dosing if indicated.
Allergies and Adverse Drug Reactions
28) History of allergy to any component of BMS-986454 or placebo (eg, excipients/diluents - refer to current version of Investigator’s Brochure for details).
29) History of allergy to acetaminophen (paracetamol), antihistamines, or corticosteroids, which will be used to address any potential reaction related to SC administration.
30) History of prior infusion/injection reactions, anaphylactic reactions, or anaphylactoid reactions to any medication regardless of severity.
Other Exclusion Criteria
31) Inability to tolerate oral medication needed for potential AE treatment.
32) Inability to be venipunctured or tolerate venous access.
33) Inability to comply with restrictions as listed in Section 6.3: Lifestyle Restrictions.
34) Participation in another clinical trial concurrent with this study.
35) Donation of blood to a blood bank or in a clinical study (except at the screening visit for this study) within 4 weeks of first study intervention administration (within 2 weeks for plasma only).
36) Blood transfusion within 4 weeks of first study intervention administration.
37) Smoking more than 10 cigarettes per day or the equivalent in other tobacco products including e-cigarettes or vapes (self-reported).
38) Recent drug abuse as defined by the current version of the International Classification of Diseases (ICD) within 2 years before the first dose administration, or positive drug screening test reflecting consumption of illicit drugs.
39) History of alcohol abuse within 2 years before the first dose administration, or positive alcohol screen.
40) Medical history or extensive physical examination findings on the abdomen which, in the best medical judgement of the investigator, would limit the ability to safely administer study intervention subcutaneously (eg, extensive scarring that does not leave enough unaffected skin to allow at least 2 injections on alternating sides of the abdomen or a past medical history of prolonged or relatively profuse bleeding/hematomas after injections).
41) Prisoners or participants who are involuntarily incarcerated. (Note: Under certain specific circumstances and only in countries where local regulations permit, a person who has been imprisoned while on study may be permitted to continue as a participant. Strict conditions apply, and Sponsor approval is required.)
Eligibility criteria for this study have been carefully considered to ensure the safety of the study participants and that the results of the study can be used. It is imperative that participants fully meet all eligibility criteria.
6.2.2 Exclusion Criteria for Part B
Medical Conditions
1) With the exception of RA, any significant medical condition (including but not limited to, neurological, GI, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or other major disorders) that, in the Investigator’s judgment, will substantially increase the risk to the participant if he or she participates in the study.
2) Participants without CCP or ACPA positivity.
Note: Given the use of citrullinated targets to determine the pharmacodynamic range and the recommended dose for further studies, evidence of citrullination via CCP/ACPA positivity is required for this first study in participants with RA.
3) Participant with severe RA as assessed by DAS28-CRP at screening or Day -1.
4) Participants with concomitant other rheumatologic/autoimmune conditions are excluded with the exception of: osteoarthritis, fibromyalgia, autoimmune thyroid disease, or secondary Sjogren syndrome provided they do not meet other exclusion criteria.
5) Participants with RA and concomitant Felty syndrome, RA-associated interstitial lung disease with functional limitation or requiring additional medication specifically to treat the interstitial lung disease, or active rheumatoid vasculitis.
6) Participant has any condition aside from RA that confounds the ability to interpret data from the study.
7) Participant has any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if the participant was to participate in the study.
8) Participant has an active acute or uncontrolled chronic systemic fungal, bacterial (including Mycobacterium tuberculosis [TB]), and/or viral infection within 30 days prior to first dosing. 9) Any major surgery within 4 weeks prior to first study intervention administration or before
4 weeks have passed from the time of the last planned PK blood collection.
Reproductive Status
10) Women who are pregnant or breastfeeding.
Prior/Concomitant Therapy
11) Inability to comply with restrictions and prohibited treatments as listed in Section 7.7: Prior and Concomitant Therapy.
12) Any prior exposure to BMS-986454 (eg, participation in Part A).
13) Participant was exposed to an investigational drug (new chemical entity) within 30 days preceding the first dose administration, or 5 half-lives of that investigational drug, if known (whichever is longer).
14) Exclusions related to therapies for RA:
a) Participant has used any biologic or targeted-synthetic DMARD within 30 days prior to the first dose administration, or 5 half-lives of that drug, if known (whichever is longer).
This includes medications such as but not limited to: IV immunoglobulin (IVIg), anti-TNF biologics, B cell depleting biologics, abatacept, JAK inhibitors, anti-IL1 biologics, or anti-IL6-R biologics. If there are questions, please, contact the Sponsor’s Clinical Trial Physician.
b) Participant has had or is planned to have intraarticular glucocorticoid injection within 3 months of Day -1 given the data on the effect of intraarticular glucocorticoid injection on citrullination.44
i) If the participant has a flare of disease activity prior to Day -1 that requires intraarticular glucocorticoid injection, the flare would constitute screen failure per inclusion and exclusion criteria because of a worsening in disease activity requiring a change in therapeutic management.
c) Oral glucocorticoid use is permitted, but the dose must be less than or eqaul too 10 mg/day prednisone or equivalent and stable for greater than 1 month before screening and the participant must be thought by his/her treating rheumatologist to be able to keep the dose level stable throughout the study intervention dosing period of this study. Further specifications on steroid use are as follows:
i) Topical and inhaled steroid use is permitted but must follow a stable regimen throughout the study and cannot be used on an as-needed basis.
ii) Inhaled steroid for non-RA conditions will not count against the maximum daily glucocorticoid dose.
iii) Intramuscular glucocorticoid administration cannot occur during the screening period and is prohibited during the study intervention dosing period of this study unless needed to urgently treat a flare of disease activity.
iv) IV glucocorticoid administration is prohibited less than 4 weeks prior to Day 1.
d) Participant is currently using anti-malarials, eg, hydroxychloroquine, chloroquine, or quinacrine or has used hydroxychloroquine, chloroquine, or quinacrine within the 30 days preceding the first dose administration given the data that hydroxychloroquine and chloroquine have effects on PAD4 and citrullination.6,46
i) This includes use of anti-malarials as part of “triple therapy” (ie, methotrexate, sulfasalazine, hydroxychloroquine [or analog]).
e) Conventional DMARDs, such as methotrexate, leflunomide, and sulfasalazine, are allowable during the study.
i) Conventional DMARDs must be at a stable dose for at least 8 weeks prior to the first
dose of study intervention, and the participant must be felt by his/her treating rheumatologist to have a reasonably high chance of remaining at that stable dose for the duration of the dosing period (ie, the treating rheumatologist was not planning to increase the dose of DMARD in the timeframe that would overlap with the study intervention dosing period). Subcutaneous MTX is allowable if the participant is willing to avoid injection at sites that are used for the study drug and can inject the MTX on a day when he/she is not being dosed with study intervention. Recording of injection-site reactions for participants on subcutaneous MTX must clearly indicate whether the injection site was used for MTX or study intervention.
f) Oral or topical non-steroidal anti-inflammatory drugs are also allowable during the study.
Other exceptions to prior/concomitant may apply on a case-by-case basis if considered not to interfere with the study objectives as agreed to by the investigator and CRO Medical Monitor. The investigator should discuss concomitant medications that cannot be held from the time of signing the ICF to the last planned PK collection timepoint.
15) Participant has used any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days prior to the first dose administration. Exceptions may apply on a case-by-case basis if considered not to interfere with the study objectives as agreed to by the investigator and CRO Medical Monitor.
16) Vaccination or plans for vaccination with any live or live attenuated vaccine within 30 days before screening, during the course of the study, or within 120 days after the last dose of study intervention.
17) Vaccination or plans for vaccination with non-live vaccines within 30 days before Day -1 until the last outpatient clinical site visit.
Physical and Laboratory Test Findings
18) With the exception of findings that are expected in a participant with mild or moderate RA in the clinical experience of the investigator or participant’s treating rheumatologist with the individual participant, participants with RA are excluded if they exhibit evidence of organ dysfunction or any clinically significant deviation from the institution’s reference range or the participant’s historical trend over the past 6 months prior to screening in physical examination, vital signs, 12-lead ECG, or clinical laboratory tests.
Note: Mild or moderate disease activity status for RA is defined according to DAS28-CRP obtained at screening.
Note: Any participant that develops an exacerbation/flare of disease activity that requires a change in baseline RA treatment dosing prior to Day -1 should be considered a screen failure, but he/she may be re-screened at a later data if meeting criteria for mild or moderate RA and again being on a stable dose level of allowable RA treatment for at least 8 weeks prior to the new planned Day -1.
19) Body mass index (BMI) is outside of the range: 18 and 32 kg/m2 inclusive at screening. BMI = weight (kg)/ [height (m)]2.
20) Participant is febrile.
21) Participant has supine systolic blood pressure (BP) less than or eqaul too 100 or greater than or equal too 140 mmHg, supine diastolic BP less than or eqaul too 50 or greater than or equal too 90 mmHg, and resting heart rate less than or eqaul too 40 or greater than or equal too 110 bpm at screening or Day -1.
22) Participant has abnormal or clinically significant 12-lead ECG, where the abnormal finding may impact the ability to interpret an AE. In addition:
a) If female, participant has a Fridericia’s corrected QT interval (QTcF) value greater than or equal too 450 msec at screening or Day -1.
b) If male, participant has a QTcF value greater than or equal too 430 msec at screening or Day -1.
23) Clinical laboratory safety test results at screening or Day -1 that are considered clinically significant by the investigator (including those within the reference range — for example, a tripling of serum creatinine from screening to Day -1, though all values remain within the reference range, may be reasonably considered clinically significant given the fold change between the 2 measurements).
Additionally, no clinical laboratory safety test result at screening or Day -1 should be in the range that constitutes a Grade 2 (moderate) or higher deviation from the reference range per the Rheumatology Common Toxicity Criteria v.2.1 (APPENDIX 4). While a single out-of-range laboratory test result may not be viewed as clinically significant, if it is related to other laboratory test results that, in totality, suggest an abnormal medical condition, then that should be factored into decision making on eligibility. For example, a hemoglobin of 12.4 gm/dL (lower limit of reference range 12.5 gm/dL) in a male may be viewed as not clinically significant. However, if the same participant also has a low mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCH), the totality of low hemoglobin and microcytosis and hypochromia would indicate anemia and the participant is ineligible.
24) Regardless of clinical significance or toxicity grading, any result that falls outside the range(s) specified below is exclusionary:
a) Absolute neutrophil count (ANC) must be above 1500 cells/mm3 but below the upper limit of the reference range for the laboratory where the study is conducted at screening and on Day -1.
b) Absolute lymphocyte count (ALC) must be above 1000 cells/mm3 but below the upper limit of the reference range for the laboratory where the study is conducted at screening and on Day -1.
c) Monocyte count must be within the reference range for the laboratory where the study is conducted at screening and on Day -1.
d) eGFR calculated by CKD-EPI must be greater than or equal too 50 mL/min/1.73 m2 to avoid AEs related with contrast use for MRI.
25) History of incompletely treated Mycobacterium tuberculosis (TB) infection, indicated by either:
a) Medical records documenting incomplete treatment for TB.
b) Participant’s self-reported history of incomplete treatment for TB.
Note: Participants with a history of TB who have undergone documented treatment accepted by the local health authorities may be eligible for study entry. The investigator must attest in the eCRF to reviewing documentation of the accepted TB treatment.
26) Participant has a positive QuantiFERON®-TB Gold (or equivalent) test result or 2 successive indeterminate QuantiFERON®-TB Gold (or equivalent) test results at screening.
27) Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, or human immunodeficiency virus (HIV)-1 and -2 antibody.
Note: Participants who received hepatitis B vaccination and who test positive for hepatitis B surface antibody and negative for both hepatitis B surface antigen and hepatitis B core antibody remain eligible for study participation.
28) Positive urine screen for drugs of abuse or positive or urine or breath alcohol test at screening or Day -1.
Section 6.4.1 has additional guidance for the investigator on retesting laboratory parameters in participants during screening up to the day of dosing if indicated.
Allergies and Adverse Drug Reactions
29) History of allergy to any component of BMS-986454 or placebo (eg, excipients/diluents - refer to current version of Investigator’s Brochure for details).
30) History of allergy to acetaminophen (paracetamol), antihistamines, or corticosteroids, which could be used to address any potential reaction(s) related to SC administration.
31) History of prior infusion reactions, anaphylactic reactions, or anaphylactoid reactions to any medication regardless of severity.
Other Exclusion Criteria
32) Contraindication to MRI; eg, magnetizable metallic parts/devices including cardiac pacemakers on and in the body, severe claustrophobia, body size incompatible with the scanner, sensitivity to gadolinium, renal insufficiency (ie, defined for purposes of this study as eGFR or GFR less than 50 mL/min/1.73 m2), and metallic tattoos. Complete contraindications are provided in the site MRI manual; however, the ultimate decision about subject appropriateness for MRI will be made by the radiologist and Investigator in accordance with local standards and ethics committees.
33) Inability to tolerate oral medication needed for potential AE treatment.
34) Inability to be venipunctured or tolerate venous access.
35) Inability to comply with restrictions as listed in Section 6.3: Lifestyle Restrictions.
36) Participation in another clinical trial concurrent with this study.
37) Donation of blood to a blood bank or in a clinical study (except at the screening visit for this study) within 4 weeks of first study intervention administration (within 2 weeks for plasma only).
38) Blood transfusion within 4 weeks of first study intervention administration.
39) Smoking more than 10 cigarettes per day or the equivalent in other tobacco products including e-cigarettes or vapes (self-reported).
40) Recent drug abuse as defined by the current version of the International Classification of Diseases (ICD) within 2 years before the first dose administration, or positive drug screening test reflecting consumption of illicit drugs.
41) History of alcohol abuse within 2 years before the first dose administration, or positive alcohol screen.
42) Medical history or extensive physical examination findings on the abdomen which, in the best medical judgement of the investigator, would limit the ability to safely administer study intervention subcutaneously (eg, extensive scarring that does not leave enough unaffected skin to allow at least 2 injections on alternating sides of the abdomen or a past medical history of prolonged or relatively profuse bleeding/hematomas after injections).
43) Prisoners or participants who are involuntarily incarcerated. (Note: Under certain specific circumstances and only in countries where local regulations permit, a person who has been imprisoned while on study may be permitted to continue as a participant. Strict conditions apply, and Sponsor approval is required.)
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
To assess the safety and tolerability of
BMS-986454 in participants with RA.
Number of participants with adverse events (AEs) [Time Frame: Up to 6 months]
Number of participants with serious adverse events (SAEs) [Time Frame: Up to 6 months]
Number of participants with physical examination findings [Time Frame: Up to 6 months]
Number of participants with vital sign measurement findings [Time Frame: Up to 6 months]
Number of participants with 12-lead electrocardiogram (ECG) findings [Time Frame: Up to 6 months]
Number of participants with clinical laboratory test findings [Time Frame: Up to 6 months]
Secondary Outcome
Outcome
TimePoints
To determine the serum PK of BMS-986454 following multiple SC administrations in participants with RA
To evaluate the potential of immunogenicity
following multiple SC administrations of
BMS-986454 in participants with RA.
Maximum observed concentration (Cmax) [Time Frame: Up to 6 months]
Concentration at the end of a dosing interval (Ctau) [Time Frame: Up to 6 months]
Trough observed plasma concentration (Ctrough) [Time Frame: Up to 6 months]
Time of maximum observed concentration (Tmax) [Time Frame: Up to 6 months]
Area under the curve over the dosing interval (AUC(TAU)) [Time Frame: Up to 6 months]
Area under the serum concentration time curve extrapolated to infinite time (AUC(INF)) [Time Frame: Up to 6 months]
Area under the serum concentration time curve from time zero to the last quantifiable concentration (AUC(0-T)) [Time Frame: Up to 6 months]
Terminal-phase half-life (T-HALF) [Time Frame: Up to 6 months]
Accumulation index of the area under the curve over the dosing interval (AI_AUC(TAU)) [Time Frame: Up to 6 months]
Accumulation index of the maximum observed concentration (AI_Cmax) [Time Frame: Up to 6 months]
Apparent total body clearance (CLT/F) [Time Frame: Up to 6 months]
Apparent volume of distribution of terminal phase (Vz/F) [Time Frame: Up to 6 months]
Number of participants with anti-drug antibody (ADA) formation [Time Frame: Up to 6 months]
Target Sample Size
Total Sample Size="46" Sample Size from India="46" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 1/ Phase 2
Date of First Enrollment (India)
10/02/2026
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="1" Months="6" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and drug levels of BMS-986454 in participants with Rheumatoid Arthritis