Dose-finding study of SAR443122 in adult participants with ulcerative colitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Research & Development

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

11 May 2023 → ongoing

Decision date (initial)

2025-05-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

sanofi research & development · sanofi research & development

External identifiers

EU CT number

2022-500290-14-01

WHO UTN

U1111-1269-6212

ClinicalTrials.gov

NCT05588843

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy, Dose response, Pharmacokinetic, Therapy, Pharmacogenomic

Assess efficacy of different doses of SAR443122 in participants with moderate to severe UC in induction treatment period.

Secondary objectives 8

1. Assess the effect of SAR443122 on endoscopic improvement in participants with UC in induction treatment period.
2. Assess the effect of SAR443122 on clinical remission and clinical response in participants with UC in induction treatment period.
3. Assess the effect of SAR443122 on the histologic improvement in participants with UC in induction treatment period.
4. Assess the effect of SAR443122 on Histologic-endoscopic mucosal improvement (HEMI) in participants with UC in induction treatment period.
5. Assess the effect of SAR443122 on disease specific quality of life in induction treatment period.
6. Assess the effect of SAR443122 on patient reported signs and symptoms of ulcerative colitis in induction treatment period.
7. Assess SAR443122 pharmacokinetics of participants with UC
8. Assess the safety and tolerability of SAR443122 in participants with moderate to severe UC over 52 weeks

Conditions and MedDRA coding

Colitis ulcerative

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participants who have clinical evidence of active Ulcerative Colitis [UC] for ≥3 months before screening as confirmed by endoscopy during the screening period.
2. Participants must have a minimum disease extent of 15 centimeters from the anal verge.
3. -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, biologics other than natalizumab (Tysabri®) or small molecules.
4. Participants on corticosteroids must be on a stable dose ≥2 weeks prior to screening and during screening period.
5. 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.
6. Participants on oral 5-aminosalicylates, mesalamine or sulfasalazine must be on a stable dose for ≥4 weeks prior to screening and during screening period.
7. Participants on advanced therapies must have 1) last administration at least 5 half-lives prior to randomization, or 2) undetectable level of the biologic in their blood prior to randomization.
8. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Women participants should not be pregnant or breastfeeding.

Exclusion criteria 36

1. Participants with Crohn’s Disease (CD).
2. Participants with diagnosis of indeterminate colitis or microscopic colitis.
3. Participants with stool sample positive for culture for aerobic pathogens or C difficile.
4. Participants with prior colectomy or anticipated colectomy during their participation in the study.
5. Participants with presence of ileal pouch or ostomy.
6. Participants with fulminant disease or toxic megacolon.
7. Participants with colonic dysplasia except for adenoma.
8. Participants with intestinal failure or short bowel syndrome requiring Total Parenteral Nutrition (TPN).
9. Participants with history of recurrent or recent serious infection that has not resolved within 4 weeks prior to randomization.
10. Participants presenting with active malignancies or recurrence of malignancy within the 5 years before screening.
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.
12. Participants presenting with fever (≥38°C) or persistent chronic or active recurring infection within 4 weeks prior to the Screening Visit requiring treatment with antibiotics, antivirals, or any history of frequent recurrent infections deemed unacceptable per investigator’s judgment.
13. Participants who were administered any live (attenuated) vaccine within 3 months prior to the randomization Visit.
14. Participants with a history of recurrent herpes zoster.
15. Participants with uncontrolled diabetes, defined as HbA1c ≥9.0% at the Screening Visit.
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.
17. Participants presenting with opportunistic infections within six months prior to screening or while receiving anti-TNF treatment in the last 6 months.
18. Participants undergoing hemodialysis or peritoneal dialysis.
19. Participants with a known history of Human Immunodeficiency Virus (HIV) infection or positive HIV serology at screening.
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. Participants that were treated for HCV and clear the virus documented by HCV RNA by PCR below the limit of quantification can be eligible.
21. Positive COVID-19 test, suspected COVID-19 infection or known exposure to COVID-19 during the screening period.
22. History of COVID-19 infection within 4 weeks prior to Screening; history of mechanical ventilation or extracorporeal membrane oxygenation (ECMO) due to COVID-19 infection within 3 months prior to Screening or with residual significant complications from COVID-19 making it unsafe for the participant to enter this study.
23. Participants presenting alcohol or drug dependency within the 2 years prior to the Screening Visit.
24. Participants with unexplained, uncontrolled, or untreated thyroid disease or unexplained abnormal serum prolactin levels at screening.
25. Participants under cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide or tacrolimus treatment within 4 weeks prior to screening.
26. Participants with previous exposure to natalizumab (Tysabri®)
27. Participants with previous exposure to RIPK1 inhibitor.
28. Participants under antidiarrheals within 2 weeks prior to screening and during screening period.
29. Participants under prednisone >25 mg/day (or equivalent).
30. Participants under budesonide >9 mg/day.
31. Participants who received intravenous corticosteroids or cytapheresis therapy within 2 weeks prior to screening or during screening.
32. Participants who were rectally administered topical 5-aminosalicylate or corticosteroids within 4 weeks prior to screening.
33. Participants who received therapeutic enema or suppository, other than required for colonoscopy or flexible sigmoidoscopy within 4 weeks prior to screening or during screening.
34. Participants who received antibiotics for UC or gastrointestinal infection within 4 weeks prior to screening.
35. Participants who have taken other investigational medications within 2 months or 5 half­lives, (whichever is longer) prior to screening.
36. Presence of significant laboratory findings at the Screening Visit.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants who achieve clinical remission at Week 12 by modified Mayo Score (mMS). The Mayo score (full MS) is a composite instrument that consists of patient reported stool frequency and rectal bleeding, endoscopy-derived measures and physician-reported assessment (PGA). The modified Mayo score is calculated omitting PGA. And an endoscopy score of 1 with no friability.

Secondary endpoints 16

1. Proportion of participants who achieve endoscopic improvement at Week 12
2. Proportion of participants who achieve clinical response at Week 12 by mMS
3. Proportion of participants who achieve clinical remission at Week 12 by full Mayo Score (MS)
4. Proportion of participants who achieve clinical response at Week 12 by MS.
5. Change from baseline on patient-reported outcome 2 (PRO2) total score (Mayo stool frequency and rectal bleeding subscores) over time
6. Proportion of participants who achieve histological improvement at Week 12
7. Proportion of participants who achieve Histologic-endoscopic mucosal improvement (HEMI) at Week 12 defined by achievement of modified Mayo endoscopic improvement and histological improvement
8. Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score at Week 12
9. Change from baseline in bowel signs and symptoms assessed by Ulcerative Colitis Patient Reported Outcome Signs and Symptoms (UC-PRO/SS) at Week 12
10. Change from baseline in abdominal signs and symptoms assessed by UC-PRO/SS at Week 12
11. Pharmacokinetic parameters: maximum concentration [Cmax]
12. Pharmacokinetic parameters: time to Cmax [tmax]
13. Pharmacokinetic parameters: area under the curve over the dosing interval [AUC0-tau]
14. Pharmacokinetic parameters: elimination half-life [t1/2z]
15. Participants with any Treatment Emergent Adverse Events (TEAEs) during induction and maintenance treatment period
16. Participants with any TEAEs during open-label treatment period

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Research & Development

Sponsor organisation

Sanofi-Aventis Research & Development

Address

1 Avenue Pierre Brossolette

City

Chilly Mazarin

Postcode

91380

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Third parties 3

Locations

11 EU/EEA countries · 51 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 96 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

32 submissions — initial application plus substantial / non-substantial modifications