CTRI/2024/12/078285 [Registered on: 18/12/2024] Trial Registered Prospectively
Last Modified On:
16/04/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A clinical study to compare immunogenicity and safety of DRL abatacept with Orencia in rheumatoid arthritis patients
Scientific Title of Study
A randomised, double-blind, multicentre study to compare the immunogenicity and safety of proposed abatacept biosimilar (DRL_AB) with Reference abatacept (Orencia®) administered subcutaneously as an add-on to methotrexate in patients with moderately to severely active rheumatoid arthritis.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
AB-01-005 Version 3.0 dated 26 Sep 2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Dr Narendra Maharaj
Designation
Head - Clinical Development
Affiliation
Dr Reddys Laboratories Ltd
Address
Dr. Reddy’s Laboratories Ltd., Biologics, Survey No. 47 and
44 (Part), Bachupally Village, Bachupally Mandal
Medchal TELANGANA 500090 India
Phone
04044644000
Fax
Email
narendramaharaj@drreddys.com
Details of Contact Person Public Query
Name
Naveen Reddy
Designation
Head - Clinical Program delivery
Affiliation
Dr Reddys Laboratories Ltd
Address
Dr. Reddy’s Laboratories Ltd., Biologics, Survey No. 47 and
44 (Part), Bachupally Village, Bachupally Mandal
Medchal TELANGANA 500090 India
Phone
04044644000
Fax
Email
naveenreddy@drreddys.com
Source of Monetary or Material Support
M/s Dr Reddys Laboratories Limited, 8-2-337, Road No. 3 Banjara Hills, Hyderabad (India) –
500034.
Primary Sponsor
Name
Dr. Reddys Laboratories Ltd.
Address
Biologics, Survey No. 47 and 44(Part), Bachupally Village,
Bachupally Mandal,Medchal Malkajgiri District, Telangana, INDIA –
500 090
Clinical Research
Department, 4th floor,
4th & 5th floor , Star
plus complex, Lam
Road, Near, Muktidham
Temple, Opp-NMC
Divisional Office,
Nashik Road , Nashik Nashik MAHARASHTRA
9822055612
drpraveenjadhav@rediffmail.com
Dr Vishnu Sharma
Avron Hospitals PVT LTD
4-Shantiniketan Park, Near Sardar Patel statue, Naranpura, Ahmedabad, Gujarat 380013 Ahmadabad GUJARAT
8511555477
drvishnusharma@yahoo.co.in
Dr Sandeep Kansurkar
Bharati Hospital and Research Centre
Bharati Vidyapeeth University Campus, Pune-Satara Road, Pune 411043, Maharastra Pune MAHARASHTRA
7738224070
sandeepkansurkar@gmail.com
Dr Chandrasekhara S
chanRe Rheumatology and lmmunology centre and Research
Clinical Research
Department, Clinical
Research Division, No.
414/65, 2oth Main,
West of Chord Road,
1st Block, Rajajinagar, Bangalore KARNATAKA
9845071151
chandrashekara_s@yahoo.com
Dr Phadmanabha Shenoy
Charm Healthcare Private Limited ( formely known as SHENOYS CARE PRIVATE LIMITED)
2nd floor, Room No. 14,
Near Toyota
Showroom, NH 66,
Nettoor, Cochin-
682040 Ernakulam KERALA
9446567000
drshenoy@drshenoycare.com
Dr Krishnamurthy Venkata Raman
Chennai Meenakshi Multispecialty Hospital Limited
Department of
Rheumatology, Clinical
Research Division, 01
(New OPD Building),
New no:70, old no: 149,
Luz Church Road,
Mylapore, Chennai
-600004, Chennai TAMIL NADU
9841041717
drvk56@gmail.com
Dr Neeraj Manikanth
Government Medical College, Kozhikode
Department of General
Medicine, Mavoor
Road, Kozhikode-
673008 Kozhikode KERALA
9447391055
nmanikath@gmail.com
Dr Smruti Ramteke
Jasleen Hospital
Clinical Research
Department, First Floor,
Room No 1, Opp.big
Bazar, Panchashil
Square, Dhantoli,
Nagpur, 440012 Nagpur MAHARASHTRA
9823514680
sramteke@rediffmail.com
Dr Subramanian Ramaswamy
JSS Hospital
M.G Road,
Mysore-570004 Mysore KARNATAKA
9945472441
Subsan05@gmail.com
Dr Pathri Sivananda
King George Hospital, Visakhapatnam
Department of Orthopaedics, King George Hospital, Andhra Medical College, 530002 Visakhapatnam ANDHRA PRADESH
9848199904
drpsivanandaresearch@gmail.com
Dr Rahul Jain
Maharaja Agrasen Superspeciality Hospital Centra
Department of General
Medicine, Basement
room no. 9 , Agrasen
aspatal marg,
sector-7,Vidhyadhar
nagar, Jaipur,
Rajasthan, 302039 Jaipur RAJASTHAN
Institutional Ethics Committee - S.R. Kalla Memorial Gastro & General Hospital
Approved
Institutional Ethics Committee BVDU
Approved
Institutional Ethics Committee Villoo Poonawalla Memorial Hospital, S No 156 Plot No. l/3A, 3B, 1, 2/3 Pune Solapur Road, Hadapsar, Pune, Maharashtra - 411028, India
Approved
Institutional Ethics Committee, Govt Medical College Kozhikode
Submittted/Under Review
Institutional Ethics Committee, JSS Medical College and Hospital
Approved
Institutional Ethics Committee, King George Hospital
Approved
Institutional Ethics Committee, Sree Sudheendra Medical Mission
Approved
Institutional Ethics Committee- Assure Care Plus Hospital
Approved
Jasleen Hospital Ethics Committee
Submittted/Under Review
Sushruta Hospital Ethics Committee
Approved
Swastic Ethics Committee, Shri Nidaan Hospital and Hope Fertility Centre
Approved
Yashoda Academy of Medical Education and Research, Yashoda Academy of Medical Education and Research
proposed abatacept biosimilar, formulated for Subcutaneous administration in Single-dose prefilled syringe containing 125 mg once-weekly
Comparator Agent
Orencia® ( EU Approved)
Reference medicinal product, formulated for Subcutaneous administration in Single-dose prefilled syringe containing 125 mg once-weekly
Inclusion Criteria
Age From
18.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
1. Patients should provide a written informed consent as per the local regulations applicable to the study site and Good Clinical Practice (GCP) guideline.
2. Male or female patients aged ≥ 18 years and ≤ 80 years at the time of signing informed consent.
3. Patients with moderately to severely active rheumatoid arthritis for at least 6 months’ duration, defined as per the American College of Rheumatology (ACR) Criteria, 1987 revision.
Active rheumatoid arthritis is defined as having:
a. Swollen Joint Count (SJC) ≥10 out of the 66 joints count
b. Tender Joint Count (TJC) ≥12 out of the 68 joints count, and
c. C-Reactive Protein (CRP) of at least 1.0 mg/dl determined using a highly sensitivity assay.
4. Patients must be on methotrexate (MTX) and folic acid for at least 3 months prior to the randomization with the below requirements.
a. Must have been treated with stable doses of MTX (between 20 to 25 mg/ week; at least 6 mg/ week for patients from other Eastern Asia countries, not exceeding allowed maximum dose in the country-specific label) for at least 4 weeks prior to randomisation.
b. Patients who cannot tolerate higher dose of MTX should be on stable and tolerable dose of MTX for 4 weeks prior to randomisation (there should be documented evidence of intolerance to MTX).
c. Patients taking MTX must be on a stable dose of folic acid (≥5 mg per week) or equivalent for at least 4 weeks prior to randomisation.
5. Patients should not be on Conventional Disease-Modifying Anti-Rheumatic Drugs (cDMARDs) other than MTX for at least 4 weeks prior to randomization (4 weeks prior for azathioprine, sulfasalazine; 8 weeks for hydroxychloroquine & chloroquine; 12 weeks for leflunomide; 24 weeks for cyclophosphamide).
6. Patients should not be on bDMARDs: these agents should have been discontinued at least 4 weeks (4 weeks prior for TNF alpha inhibitors; 24 weeks for rituximab; 4 weeks or half of biological half-life for other bDMARDs whichever is longer) prior to randomization.
7. Patients on glucocorticoids should not be receiving more than 10 mg oral prednisone/ prednisolone or equivalent per day, and those receiving should be using stable dose for at least 6 weeks prior to randomisation.
8. For patients receiving Nonsteroidal Anti-inflammatory Drugs (NSAIDs) for the last 4 weeks prior to randomisation:
a. Should be taking a stable dose NOT higher than the maximum recommended dose for the agent in the Prescribing Information of the country where the study centre is located.
b. NSAIDs are allowed except for the 12h before the scheduled efficacy assessment visit (24h for oxicams and other single daily dose or less frequently administered agents); Details of permitted and prohibited medication in the current study has been captured at Section 6.9.
9. Women of childbearing potential should have a negative pregnancy test and should agree to use highly effective measures of contraception(as per the Clinical Trial Facilitation Group (CTFG) guidelines 2020) and not to donate or cryopreserve ova during the course of the study and for at least 6 months after the last dose of the study drug.
OR
Male patients should be permanently sterile by bilateral orchidectomy or agree to use appropriate contraception methods (Per the Clinical Trial Facilitation Group (CTFG) guidelines 2020) and not to donate or cryopreserve sperm during the study and for at least 6 months after the last dose of study drug.
10. Patients must be able to self-administer or must have help to administer the study treatment by caregiver.
11. Patients must be able to comply with all study requirements in the opinion of the Investigator.
ExclusionCriteria
Details
1. Patients who have received prior treatment with abatacept.
2. Patients who have received prior treatment with JAK inhibitors within the last 16 weeks of randomization (e.g., tofacitinib, abrocitinib, baricitinib, upadacitinib, filgotinib etc.).
3. Patients who have received treatment with IV gamma globulin or plasmapheresis within 6 months of randomisation.
4. Patients with known contraindication to treatment with abatacept, including, but not restricted to hypersensitivity to abatacept or any excipients (dibasic sodium phosphate anhydrous, monobasic sodium phosphate monohydrate, L-Histidine, sodium chloride, poloxamer and sucrose) in the study formulations.
5. Patients who need concomitant rheumatoid arthritis therapies other than a. MTX with folic acid (at a dose of at least 5 mg per week [or equivalent]) (MTX and folic acid will be kept at a stable dose during the study), Folinic acid at the same dose of folic acid, can be given in place of folic acid if it is allowed by the local label. Patient should take the same folate supplementation throughout the duration of the study.
b. NSAIDs at approved doses kept at stable doses during the study
c. Corticosteroids at a maximum daily dose of 10 mg of oral prednisone or equivalent kept stable during the study
Also, patients who cannot maintain an analgesics-free period of appropriate duration (12 hr for analgesics in general, 24 hr for oxicams and other single daily or less frequently administered drugs) before patient evaluation visit.
Note: Aspirin at anti-aggregant doses (up to 325 mg per day) is not considered as an analgesic.
6. Patients who have received any treatment with intra-articular injections (e.g., corticosteroids) required for a flare-up within 4 weeks prior to randomisation.
7. Patients with functional class IV as defined by the ACR Classification of Functional Status in RA.
8. Patients with other inflammatory diseases that might confound the evaluation of the efficacy (e.g., Crohn’s disease, ulcerative colitis).
Note: Sjogren syndrome secondary to RA is allowed.
9. Patients who have received any investigational drug within 30 days or 5 times half-life, whichever is longer, prior to randomization (or longer as per the local regulation of the country). Patients participating or participated in another clinical trial evaluating a bDMARD for RA within the last year before screening are not eligible for this trial.
10. Patients with a known history of or presence of clinically significant cardiovascular (any patient with New York Heart Association (NYHA) III or IV functional status is to be excluded), haematological, renal, or liver disease. Patients with any other disorder or treatment that, in the Investigator’s opinion, may interfere with the safety of the patient, the validity of the study evaluations, or the patient compliance to the study procedures such as neurological diseases, psychiatric diseases, respiratory diseases, gastrointestinal diseases, endocrinological diseases, metabolic diseases or any other diseases. Special focus should be given to lung conditions to ensure it is sufficiently close to normal to avoid excessive risks upon study participation.
11. Patients with any history or current presence of known demyelinating disease.
12. Patients with any history of or presence of an active neoplasia except for successfully treated (at least five years in advance) non-metastatic cutaneous squamous cell or basal cell carcinoma and or localised carcinoma in situ of the cervix.
13. Patients with renal impairment (Cockcroft-Gault creatinine clearance less than 60 mL per min) or liver function impairment (bilirubin greater than 1.25 x Upper Limit of Normal (ULN) (2.5xULN with indirect bilirubin contributing to greater than 80% of the total bilirubin as per the laboratory test for patients with documented Gilbert syndrome), International Normalised Ratio (INR) greater than 1.25, Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) greater than 1.5 x ULN) at screening, unless the values are not clinically significant as per the investigator.
14. Patients with history of chronic alcoholism or drug abuse or other addictions (for the purposes of the study in the opinion of the Investigator; testing not necessary).
15. Patients with diseases that have immune suppression in their clinical course and or need for treatment with immune suppressive treatments such as patients with an organ graft requiring maintenance immune suppression.
16. Clinically significant chronic obstructive pulmonary disease (COPD) in the opinion of the Investigator.
17. Patients with latent tuberculosis (TB) including patients with positive and indeterminate QuantiFERON-TB test at screening (QuantiFERON-Gold TB or other validated TB screening Interferon Gamma Release Assay). Patients with history of active TB within 3 years of the start of study treatment can only be included if documentation of a completed treatment is provided.
Note: For indeterminate results, two repeats are allowed. Patients may be re-screened and randomised after completing at least 3 months of prophylactic treatment with relevant appropriate medications as a standard approach, and treatment confirmed as effective in patient documentation before randomization. In emergent situations, when the patient needs quick therapy for RA, 4 weeks of prophylactic treatment can be considered appropriate.
18. Patients with active TB, unrecovered hepatitis B, herpes zoster including the period of post-herpetic neuralgia within 1 year of randomisation, or any other ongoing clinically relevant active infection, even if localised.
19. Patients with positive screening for hepatitis B surface antigen (HBsAg), hepatitis C or Human Immunodeficiency Virus (HIV).
20. Patients who received live virus vaccination within 3 months prior to randomisation or intention to receive live virus vaccination during the trial or up to 3 months after the last dose of the study drug.
21. Patients with acute or chronic unhealed clinically significant external wounds.
22. Female patients who are currently pregnant or breastfeeding.
23. Patients who are considered unreliable to follow study requirements and restrictions, in the opinion of the Investigator.
24. Patients who had major surgery including joint surgery within 8 weeks prior to randomisation or planned major surgery within 12 months following randomisation.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Comparison of the incidence and prevalence of ADAs (towards whole abatacept and or CTLA 4) and NAb between Dr Reddys Abatacept and RMP in patients with active rheumatoid arthritis
Comparison of titers between Dr Reddys Abatacept and RMP dosed patients with active rheumatoid arthritis
Baseline through scheduled timepoints till Week 56 or EOS
Secondary Outcome
Outcome
TimePoints
Efficacy:
Comparison of the following evaluations in both arms:
Change from Baseline in DAS28 CRP
Change from Baseline in DAS28 ESR
Proportion of patients achieving EULAR moderate or good response
Proportion of patients achieving ACR20 or 50 or 70 response
Safety:
Incidence of TEAEs, SAEs and AESI
Incidence of hypersensitivity reactions and Injection site reactions
TMAC:
To compare Population PK parameters
Pharmacodynamics:
Change from baseline in PD parameters
Efficacy:
Baseline, Week 13, Week 25, Week 37, and Week 53
Safety:
Baseline till Week 56 or EOS.
TMAC:
Baseline through scheduled time points till Week 56 or EOS
Pharmacodynamics:
Baseline through scheduled time points
Target Sample Size
Total Sample Size="100" Sample Size from India="100" 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 3
Date of First Enrollment (India)
01/12/2025
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="7" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Closed to Recruitment of Participants
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 compare the immunogenicity and safety of proposed abatacept biosimilar (DRL_AB) with Orencia® administered by the SC route as an add-on to MTX in the treatment of patients with moderate to severe RA. The study duration will be up to 60 weeks including 4 weeks screening period. The drug administration will be up to Week 52 followed by EOS at Week 56 (4 weeks after the last dose).