A Global Phase-III Clinical Trial to be conducted in adult population who are suffering from moderate to severe ulcerative colitis to evaluate the efficacy and safety of Test Drug (SAR443122) vs Placebo.
- Conditions
- Health Condition 1: K519- Ulcerative colitis, unspecified
- Registration Number
- CTRI/2023/06/053613
- Lead Sponsor
- Sanofi-Aventis Recherche & Développement
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
I 02. Participants who have clinical evidence of active Ulcerative Colitis [UC] for =3 months before screening as confirmed by endoscopy during the screening period and within no more than 10 days prior to randomization.
I 03. Active moderate to severe UC at baseline as defined by a modified Mayo score of 5-9 (without the PGA, with a minimum score of RB =1 and SF =1, endoscopy subscore =2 confirmed by central reader, and a minimum sum of all subscores of 5).
I 04. Participants must have a minimum disease extent of 15 centimeters from the anal verge.
I 05. Participants are inadequate or non-responders, have shown loss of response, or are
intolerant to at least 1 of following approved treatments: amino-salicylate, corticosteroids, immunosuppressants or biologics (anti-TNF alpha, anti-integrin, anti-IL-12/IL-23, or anti- IL-23) other than natalizumab (Tysabri®).
I 06. Participants on corticosteroids must be on a stable dose =2 weeks (dose not exceeding 25 mg/day prednisone or equivalent) prior to screening and during screening period.
I 07. Participants on methotrexate, azathioprine or 6- mercaptopurine must be on treatment for at least 8 weeks prior to screening; and on a stable dose =4 weeks prior to screening and during screening period.
I 08. Participants on oral 5-aminosalicylates, mesalamine or sulfasalazine must be on a stable dose for =4 weeks prior to screening and during screening period.
I 09. Participants on biologics must have been administered 1) at least 5 half-lives prior to start of randomization, or 2) participant must have an undetectable level of the biologic in their blood prior to randomization
1.10 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 are eligible to participate if they agree to the following during the study intervention period and for at least 5 days after the last dose of IMP, corresponding to time needed to eliminate study intervention(s) (eg, 5 terminal half-lives).
- Refrain from donating sperm .
PLUS, either:
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.
OR
- Must agree to use contraception/barrier as detailed below:
A male condom and an additional highly effective contraceptive method
when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.
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 non-childbearing potential (WONCBP) as defined in Appendix 4
Contraceptive and barrier guidance (
OR
- Is a WOCBP and agrees to use a contraceptive method that is highly effective (with a failure rate of <1% per year),
preferably with low user dependency, as described in Appendix 4 Contraceptive and barrier guidance, during the study intervention period and for at least 5 days, corresponding to the time needed to eliminate any study intervention(s) (eg, 5 terminal half-lives) plus 30 days (a menstrual cycle) after the last dose of study intervention and agrees not to donate egg
E 01. Participants with Crohn’s Disease (CD).
E 02. Participants with diagnosis of indeterminate colitis.
E 03. Participants with stool sample positive for culture for aerobic pathogens including: Aeromonas, Plesiomonas, Shigella, Yersinia, Campylobacter and E. Coli spp. or positive for Clostridium difficile B toxin in stools.
E 04. Participants with prior colectomy or anticipated colectomy during their participation in the study.
E 05. Participants with presence of ileal pouch or ostomy.
E 06. Participants with fulminant disease or toxic megacolon.
E 07. Participants with colonic dysplasia except for adenoma.
E 08. Participants with intestinal failure or short bowel syndrome requiring Total Parenteral Nutrition (TPN).
E 09. Participants with history of recurrent or recent serious infection (eg, pneumonia, septicemia as defined by the Investigator).
E 10. Participants presenting with malignancies except history of basal cell carcinoma or in-situ cervical carcinoma.
E.11. Participants with a history or presence of another significant illness that according to the Investigator’s judgment would adversely affect the subject’s ability to participate in this study such as (and not limited to) cardiovascular (including stage III or IV cardiac failure according to New York Heart Association (NYHA), renal, neurological, endocrine, gastrointestinal, hepatic disease, metabolic, pulmonary or lymphatic disease.
E.12 . Participants presenting with fever (=38°C) or persistent chronic or active recurring infection requiring treatment with antibiotics, antivirals, or antifungals within 4 weeks prior to the Screening Visit, or history of frequent recurrent infections unacceptable per Investigator’s judgment.
E 13. Participants who were administered any live (attenuated) vaccine within 3 months prior to the randomization Visit.
E 14. Participants with a history of recurrent herpes zoster.
E 15. Participants with uncontrolled diabetes, defined as HbA1c =9.0% at the Screening Visit.
E 16. Participants with active tuberculosis (TB) or non-tuberculous mycobacterial infection, or a history of incompletely treated active or latent TB per local guidelines will be excluded from the study unless it is documented by a specialist that the participant has been adequately treated and can now start treatment with the RIPK1 kinase inhibitor
Also, participants with a positive PPD test, Mantoux test or Quantiferon-TB Gold test at Screening indicating latent TB or another mycobacterial infection, will be excluded from the study. Positive PPD or Mantoux is acceptable if it can be explained by a documented
BCG-vaccination.
E 17. Participants presenting with opportunistic infections within six months prior to screening or while receiving anti-TNF treatment in the last 6 months. The participants presenting infection that have been treated and that result in no sequelae or consequences can be randomized in the study if they meet the other entry criteria.
E 18. Participants undergoing hemodialysis or peritoneal dialysis.
E 19. Participants with a known history of Human Immunodeficiency Virus (HIV) infection or positive HIV serology at screening.
E 20. Participants with Positive Hepatitis B surface antigen (HBsAg) or positive Hepatitis B core antibody (HBcAb); and/or positive Hepatitis C antibody (HCV) at the Screening Visit.
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Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Part A+B (induction treatment): <br/ ><br>Assess efficacy of different doses of SAR443122 in participants with moderate to severe UC.Timepoint: Proportion of participants who achieve clinical remission at Week 12 by modified Mayo Score (mMS)
- Secondary Outcome Measures
Name Time Method