A study to investigate efficacy and safety of SAR441566 in patients with ulcerative colitis
Scientific Title of Study
A Phase 2, multinational, multicenter, randomized, doubleblind,
placebo-controlled, dose-ranging study to evaluate
the efficacy and safety of SAR441566 in adults with
moderate-to-severe ulcerative colitis.
Trial Acronym
SPECIFI-UC
Secondary IDs if Any
Secondary ID
Identifier
DRI17822 Version number 1.0, 19-Dec-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 J Dinesh Kumar
Designation
Medical Advisor
Affiliation
Sanofi Healthcare India Private Limited
Address
Sanofi House, L&T Business Park, Saki-Vihar Road, Powai
Mumbai MAHARASHTRA 400072 India
Phone
09790753835
Fax
Email
DineshKumar.Jeyaprakash@sanofi.com
Details of Contact Person Public Query
Name
Mr Laxman Deshmukh
Designation
Clinical Project Leader
Affiliation
Sanofi Healthcare India Private Limited
Address
Sanofi House, CTS No. 117-B, Land T Business Park, Saki Vihar Road, Powai, Mumbai-
Mumbai MAHARASHTRA 400072 India
Phone
09730652540
Fax
Email
laxman.deshmukh@sanofi.com
Source of Monetary or Material Support
Sanofi Healthcare India Pvt. Ltd, Sanofi House, CTS No.117-B, L&T Business Park, Saki Vihar Road, Powai Mumbai:400072
Primary Sponsor
Name
Sanofi Healthcare India Pvt Limited
Address
Sanofi House, CTS No.117-B, L&T Business Park, Saki Vihar Road, Powai Mumbai:400072
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Argentina Australia Belgium Brazil Canada Chile China Czech Republic France Germany Greece India Italy Japan New Zealand Poland South Africa Spain Turkey United States of America
Sites of Study
No of Sites = 11
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Manas Panigrahi
All India Institute of Medical Sciences (AIIMS)
Bhubaneswar-751019 Khordha ORISSA
9438884267
dr.manaskumarpanigrahi1@gmail.com
Dr Vineet Ahuja
All India Institute Of Medical Sciences (AIIMS)
Ansari Nagar, New Delhi – 110 029 New Delhi DELHI
9810707170
vineet.aiims@gmail.com
Dr Rupa Banerjee
Asian Hospital
Somajiguda, Hyderabad-500082 Hyderabad TELANGANA
9849287530
dr_rupa_banerjee@hotmail.com
Dr Nitin Behl
Deep Hospital
Model Town, Ludhiana-141002 Ludhiana PUNJAB
8427000080
drbehlresearch@gmail.com
Dr Rajib Sarkar
IPGMER
A.J.C Bose Road, Kolkata-700020 Kolkata WEST BENGAL
9477371103
dr.rajibsarkar2023@gmail.com
Dr Jayanta Samanta
Postgraduate Institute of Medical Education and Research (PGIMER)
Dose formulation: Oral Unit dose strength(s): 100 mg Intervention description: For each dose arm, the participant will take 2 tablets in the morning and 2 in the evening (4 tablets total per day). Arm 200 mg BID: 4 tablets of SAR441566 100 mg daily. Arm 100 mg BID: 2 tablets of SAR441566 100 mg daily Arm 100 mg QD: 1 tablet of SAR441566 100 mg daily Arm Placebo: 0 tablet of SAR441566 Route of Administration: Oral Treatment duration: up to 52 weeks
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1. Male or female participants aged 18 to 75 years inclusive, at the time of signing the informed consent.
2. Participants who have clinical evidence of active UC for more than equal to 3 months before screening and confirmed by endoscopy during the screening period.
3. Active moderate-to-severe UC at screening as defined by a mMS of 5 to 9 (without the PGA, with a minimum RB subscore more than equal to 1, a minimum SF subscore more than equal to 1, a mMES more than equal to 2 confirmed by central reader, a minimum sum of all subscores of 5, and a disease extent more than 15 cm from the anal verge.
4. Must have received prior treatment for UC (either a or b below or combination of both)-
a-No prior exposure to AT, but having inadequate response to, loss of response to or intolerance to standard treatment with any of the following compounds- 5-ASA, 6-MP, AZA, MTX, oral or intravenous (IV) corticosteroids or history of corticosteroid dependence (defined an inability to successfully taper corticosteroids without recurrence of UC).
OR
b-Inadequate response to, loss of response to or intolerance to treatment with more than equal to 1 approved
5. AT such as a biologic agent (such as TNF antagonists, anti-integrin other than natalizumab, anti-IL-12/23, anti-IL-23, or experimental biologic UC therapeutics), or a small molecule (such as a JAKi or S1PRm) for UC. The treatment must have been discontinued according to the following timeline-
-anti-TNF, anti-IL12/23 and anti-IL23 therapies at least 8 weeks before randomization.
-vedolizumab, ustekinumab or rizankizumab treatment at least 8 weeks before randomization.
-experimental biologic UC therapy at least 8 weeks before randomization or 5 times the terminal half-life of the investigational drug, whichever is longer.
-JAKi or S1PRm at least 2 weeks before randomization.
-experimental biologic small molecule at least 2 weeks before randomization or 5 times the terminal half-life of the IMP, whichever is longer.
6. Participant may be receiving a therapeutic dosage of at least 1 of the following drugs-
-Oral 5-ASA compounds- prescribed dose must be stable for at least 2 weeks before screening colonoscopy or stopped treatment at least 2 weeks prior to screening colonoscopy.
-Oral corticosteroids must be at a prednisone-equivalent dose of 25 mg/day, or 9 mg/day of budesonide, and have been at a stable dose for at least 2 weeks prior to the screening colonoscopy or stopped at least 2 weeks prior to screening colonoscopy.
-AZA, 6-MP, or MTX- if the prescribed dose has been stable for at least 4 weeks before screening endoscopy, or, if stopped, medication must have been discontinued or at least 4 weeks prior to screening endoscopy to be considered eligible for enrollment.
Sex, contraceptive/barrier method and pregnancy testing requirements/breastfeeding
Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
a-Male participants
Male participants who are sexually active with female partner(s) of childbearing potential must agree to practice the protocol-specified contraception during the study and for up to 3 months, after the last dose of study intervention which will allow for one complete cycle of spermatogenesis following study drug discontinuation. Males must refrain from donating sperm during the study treatment period and for up to 3 months after the last dose of study intervention.
b-Female participants
-A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies-
- Is a woman of nonchildbearing potential (WONCBP)
OR
- Is a woman of childbearing potential (WOCBP) and agrees to use a contraceptive method that is highly effective (with a failure rate of less than 1percent per year), preferably with low user dependency, during the study intervention period (to be effective before starting the intervention) and for at least 3 months after the last administration of study intervention and agrees not to donate or cryopreserve eggs (ova, oocytes) for the purpose of reproduction during this period.
-A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) at screening and a negative urine pregnancy test before the first administration of study intervention. 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.
a-WOCBP may participate and include who are- infertile due to surgical sterilization
b-(hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as
c-Mullerian agenesis, or post-menopausal - defined as either-
d-A woman more than equal to 50 years of age with an intact uterus, not on hormone therapy, who has had
e-either
f--cessation of menses for at least 1 year, or
g--at least 6 months of spontaneous amenorrhea with a follicle-stimulating hormone
h--(FSH) more than 40 mIU/mL,
i--A woman more than equal to 55 years of age not on hormone therapy, who has had at least 6 months of
j--spontaneous amenorrhea, or
k--A woman at least 55 years of age with a diagnosis of menopause prior to starting hormone replacement therapy.
Informed Consent
Capable of giving signed informed consent as described in Section 10.1 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. In countries where legal age of majority is above 18 years, a specific ICF must also be signed by the participants legally authorized representative.
ExclusionCriteria
Details
Medical conditions
1. Participants with active CD, indeterminate colitis, ischemic colitis, microscopic colitis.
2. Participants with the following ongoing known complications of UC:
-Fulminant colitis
-Toxic megacolon
-Or any other manifestation that might require bowel surgery while enrolled in the study
-Participant with ostomy or ileoanal pouch
3. Participants with prior colectomy or anticipated colectomy during their participation in the study.
4. Participants with fecal sample positive for ova or parasites, or any aerobic pathogens at screening including: Aeromonas, Plesiomonas, Shigella, Salmonella, Yersinia, Campylobacter, or E. coli sp. or positive for
Clostridium difficile B toxin in stools.
5. At the screening visits, participants with positive-
- Hepatitis B surface antigen (HBsAg), or Hepatitis B core antibody immunoglobulin M (HBcAb IgM) or HBcAb total, or Hepatitis C virus antibody (HCVAb) confirmed by positive HCV-RNA. (Participants with a positive HCVAb and negative HCV-RNA who have documented evidence of completing HCV anti-virals with cure may be included)
- Any other active, chronic or recurrent infection, including recurrent or disseminated herpes zoster or disseminated herpes simplex.
6. Participants with a known history of human immunodeficiency virus (HIV) infection or positive HIV-1 or HIV-2 serology at screening.
7. Participants with active tuberculosis or who meet tuberculosis exclusionary parameters:
- Active TB or a history of incompletely treated TB.
- Undergoing treatment for latent TB infection (LTBI).
- Positive QuantiFERON-TB test at Screening visit. Indeterminate QuantiFERON-TB may be repeated once during screening period and will be considered positive if retest results are positive or indeterminate.
- Current household contacts with active TB.
- Received BCG-vaccination within 12 months prior to screening.
-Participants meeting all the following TB-related criteria would not be excluded:
- documented completed appropriate LTBI treatment, OR treated for active TB infection (with a treatment regimen as per local guidelines),
AND
- have obtained consultation with a specialist to rule out or treat active TB infection
AND
- for whom review and approval from Sponsor have been granted are eligible.
Note- TB testing is mandatory to rule out active/latent TB and a blood sample for QuantiFERON-Tuberculosis Gold Interferon- Gamma Release Assay (IGRA) testing should be sent to the central laboratory.
8. Participants presenting with active malignancies, lymphoproliferative disease, or recurrence of either, within the 5 years before screening (with the exception of the following treated malignancies that are allowed in the study- basal cell carcinoma, adequately squamous cell carcinoma in situ of the skin or cervical carcinoma in situ).
9. Participants with adenomatous colonic polyps or colonic mucosal dysplasia (low- or high-grade) not excised or incompletely excised.
10. History of colonic mucosal dysplasia or presence of adenomatous colonic polyps not removed OR presence of colonic mucosal dysplasia or adenomatous colonic polyps not removed during colonoscopy at screening visit.
11. If the participant has extensive colitis for more than equal to 8 years or disease limited to left side of colon (ie, distal to splenic flexure) for more than 10 years, regardless of age, a colonoscopy within 1 year of the screening visit is required to survey for dysplasia. Participants with dysplasia or cancer identified on biopsies will be excluded.
12. Participants with active diverticulitis, history of gastrointestinal perforation (other than appendicitis or mechanical injury), or significantly increased risk for gastrointestinal perforation per Investigator judgment.
13. Female participants who is pregnant, breastfeeding, or is considering becoming pregnant during the study or within 3 months after the last dose of study drug.
14. Participants with a history of allergic reaction or significant sensitivity to components of the study drug (and its excipients).
15. Participants with any of the following cardiovascular conditions or thrombotic conditions at screening-
- Participants with New York Heart Association Class III or higher heart failure
- Participants with recent (within past 6 months before screening) cerebrovascular accident, myocardial infarction, coronary stenting,
- Participants with current uncontrolled hypertension as defined by a confirmed systolic blood pressure (BP) more than 160 mmHg or diastolic BP more than 100 mmHg;
- Participants with known inherited conditions that predispose to hypercoagulability.
16. Participants with a history of diagnosis of demyelinating disease such as but not limited to:
-Multiple Sclerosis
-Acute Disseminated Encephalomyelitis
Prior/concomitant therapy
18. Participants with usage of below prior/concomitant medications
-Use of strong CYP3A4 inhibitors or strong CYP3A4 inducers within 7 days (for inhibitors) and 14 days (for inducers), respectively, or 5 times the elimination half-life of the medication (whichever is longer) prior to the first IMP administration, or the need for ongoing treatment with concomitant oral or intravenous therapy with strong CYP3A4 inhibitors or strong CYP3A4 inducers during the screening.
-Use of P-gp inhibitors or inducers which clinically alter the systemic exposure of the victim drug by at least 2-fold within 7 days (for inhibitors) and 14 days (for inducers), respectively, prior to start of IMP administration or within 5 times the elimination half-life of the medication whichever is the longer, or the need for ongoing treatment with these P-gp inhibitors or inducers during the screening.
-Use of P-gp substrates with a narrow therapeutic index, for which the label indicates that P-gp inhibition led to an increase in systemic exposure, within 7 days prior to start of IMP administration or within 5 times the elimination half-life of the medication (whichever is the longer) or the need for ongoing treatment with these substrates during the screening.
-Sensitive CYP1A2 substrates with a narrow therapeutic index within 7 days prior start of IMP administration or 5 time the elimination half-life of the medication whichever is the longer, or the need for ongoing treatment with concomitant oral or IV therapy with these drugs during the screening.
19. Participants on antidiarrheals or opiates within 2 weeks prior to screening or during screening period.
20. The use of concomitant medications that prolong the QT/QTc interval with known risk of TdP .
21. Infection(s) requiring treatment with IV anti-infectives within 30 days prior to the screening visit or oral/intramuscular anti-infectives within 14 days prior to the screening visit.
22. Participants requiring or receiving any parental nutrition and/or exclusive enteral nutrition.
23. Participants who received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to screening.
24. Participants who received fecal microbial transplantation within 30 days prior to screening.
25. Participants who have ever been exposed to 4 or more marketed ATs including biologics or small molecules (JAKi or S1PRm) during their lifetime. Exposure is defined as having received one complete dose of the AT.
26. Participants who have ever been exposed to natalizumab (Tysabri) or oral carotegrast methyl (Carogra), or received any of the following agents-
- 4 or more biologic anti-TNFs during their lifetime, or exposure to Adalimumab, certolizumab, golimumab, infliximab, or an anti TNF biosimilar within 8 weeks prior to randomization Vedolizumab, ustekinumab, or rizankizumab within 12 weeks prior to randomization
Note: If there is proper documentation of an undetectable drug level measured by a commercially available assay for any of the approved biologics above, there is no minimum washout prior to randomization.
27. Participants with previous exposure to a JAKi (eg, tofacitinib, filgotinib, upadacitinib) or S1PRm (eg, ozanimod, etrasimod) within 2 weeks prior to the screening visit.
Note- Participants who received a JAK inhibitor prior to study entry may be enrolled if they have had an inadequate response or loss of response to the JAKi.
28. Participants who received IV corticosteroids within 14 days prior to screening or during screening period.
29. Participants who received therapeutic enema(s) or suppository(ies) (eg, rectal 5-ASA/ corticosteroids), other than required for colonoscopy, within 14 days prior to the colonoscopy used for screening or during the treatment.
30. Participants who received apheresis (eg, adacolumn apheresis) within 60 days prior to screening or during screening period.
31. Participants who received antibiotics for UC or gastrointestinal infection within 4 weeks prior to screening.
32. Participants with cannabis use, either recreational or for medical reasons, within 14 days prior to screening visit or any history of clinically significant (as per Investigators judgement) drug or alcohol abuse in last 6 months.
33. Participants who have been the recipient of an organ transplant which requires continued immunosuppression.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
To assess efficacy of different doses of SAR441566 on clinical remission in participants with moderate-to-severe UC
52 weeks
Secondary Outcome
Outcome
TimePoints
To assess the effect of different doses of SAR441566 on clinical response in participants with moderate-to-severe UC
52 weeks
Target Sample Size
Total Sample Size="204" Sample Size from India="36" 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 2
Date of First Enrollment (India)
15/07/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
15/06/2025
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="2" Months="6" Days="15"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Open to Recruitment
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
This is a Phase 2, multinational,
multicenter, randomized, double-blind, placebo-controlled, dose ranging study
to evaluate the efficacy and safety of SAR441566 in adults with moderate-to-severe
UC. The target population of the study
is participants with moderate to severely active UC, defined as an active
disease with a modified Mayo Score (mMS) from 5 to 9, with a modified Mayo Endoscopic Subscore (mMES) more than equal to 2, as
confirmed by a central reader, an average daily very soft or liquid stool
frequency (SF) more than equal to1, and average rectal bleeding (RB) subscore more than equal to 1 at screening. Participants on stable doses of
standard therapies such as aminosalicylates (ASAs), oral steroids, thiopurines
(azathioprine [AZA] or 6-mercaptopurine [6-MP]) or methotrexate (MTX) and not
on medications prohibited due to the risk of drug-drug interaction (DDI) or
known risk of Torsade de Pointes (TdP) would be eligible for the study. Participants who do not meet the inclusion
criteria or meet one of the exclusion criteria will not be enrolled.