Dose-finding Study of SAR443122 in Adult Participants With Ulcerative Colitis

Colitis Ulcerative Clinical Trial

— RESOLUTE  

Official title:

A Randomized, Double-blind, Placebo Controlled, Dose-finding Study to Assess the Efficacy and Safety of SAR443122 in Adult Patients With Moderate to Severe Ulcerative Colitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05588843
• Other study ID #: DRI16804
• Secondary ID: U1111-1269-62122
• Status: Recruiting
• Phase: Phase 2
• Start date: November 25, 2022
• Est. completion date: September 9, 2026

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free number for US &
• Phone: 800-633-1610
• Email: contact-us[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind, placebo controlled, dose-ranging Phase 2 study. The primary objective is to evaluate the efficacy and safety of SAR443122 compared to placebo in participants with moderate to severe UC. Dose selection for further clinical development will be based on the multiple efficacy, safety and PK parameters. The study consists of 4 parallel arms (3 dose groups of SAR443122 vs placebo) to assess the efficacy and safety of SAR443122 in participants with moderate to severe UC. All participants will receive a total of 52 weeks (a 12-week induction treatment phase and a 40-week maintenance phase) of study treatment, except if treatment should be discontinued per investigator's assessment. At the end of the first 12 weeks of induction treatment, all participants in clinical response or remission will be offered study treatment up to 40 weeks and will continue with the same blinded treatment that was assigned. Participants who do not achieve clinical response or remission at the end of the initial 12 weeks induction treatment will roll over in an open-label treatment arm and will be treated with SAR443122 at the highest tested dose. In addition, participants from the maintenance treatment that lose clinical efficacy at any time up to V10/Week 40 (Week 28 of maintenance) will be offered to roll over in the open-label treatment arm with SAR443122 at the highest dose.

Description:

Total study duration per participant will be up to 58 weeks, including a screening period of up to 4 weeks, a treatment period up to 52 weeks and a post-treatment follow-up period of 2 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 182
• Est. completion date: September 9, 2026
• Est. primary completion date: November 19, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Participants who have clinical evidence of active Ulcerative Colitis [UC] for =3 months before screening as confirmed by endoscopy during the screening period.
• Participants must have a minimum disease extent of 15 centimeters from the anal verge.
• 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 other than natalizumab (Tysabri®) or small molecules.
• Participants on corticosteroids must be on a stable dose =2 weeks prior to screening and during screening period.
• 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.
• Participants on oral 5-aminosalicylates, mesalamine or sulfasalazine must be on a stable dose for =4 weeks prior to screening and during screening period.
• 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.
• 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:

• Participants with Crohn's Disease (CD).
• Participants with diagnosis of indeterminate colitis or microscopic colitis.
• Participants with stool sample positive for culture for aerobic pathogens or C difficile.
• Participants with prior colectomy or anticipated colectomy during their participation in the study.
• Participants with presence of ileal pouch or ostomy.
• Participants with fulminant disease or toxic megacolon.
• Participants with colonic dysplasia except for adenoma.
• Participants with intestinal failure or short bowel syndrome requiring Total Parenteral Nutrition (TPN).
• Participants with history of recurrent or recent serious infection that has not resolved within 4 weeks prior to randomization.
• Participants presenting with active malignancies or recurrence of malignancy within the 5 years before screening.
• 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.
• 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.
• Participants who were administered any live (attenuated) vaccine within 3 months prior to the randomization Visit.
• Participants with a history of recurrent herpes zoster.
• Participants with uncontrolled diabetes, defined as HbA1c =9.0% at the Screening Visit.
• 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.
• Participants presenting with opportunistic infections within six months prior to screening or while receiving anti-TNF treatment in the last 6 months.
• Participants undergoing hemodialysis or peritoneal dialysis.
• Participants with a known history of Human Immunodeficiency Virus (HIV) infection or positive HIV serology at screening.
• 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.
• Positive COVID-19 test, suspected COVID-19 infection or known exposure to COVID-19 during the screening period.
• 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.
• Participants presenting alcohol or drug dependency within the 2 years prior to the Screening Visit.
• Participants with unexplained, uncontrolled, or untreated thyroid disease or unexplained abnormal serum prolactin levels at screening.
• Participants under cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide or tacrolimus treatment within 4 weeks prior to screening.
• Participants with previous exposure to natalizumab (Tysabri®).
• Participants with previous exposure to RIPK1 inhibitor.
• Participants under antidiarrheals within 2 weeks prior to screening and during screening period.
• Participants under prednisone >25 mg/day (or equivalent).
• Participants under budesonide >9 mg/day.
• Participants who received intravenous corticosteroids or cytapheresis therapy within 2 weeks prior to screening or during screening.
• Participants who were rectally administered topical 5-aminosalicylate or corticosteroids within 4 weeks prior to screening.
• Participants who received therapeutic enema or suppository, other than required for colonoscopy or flexible sigmoidoscopy within 4 weeks prior to screening or during screening.
• Participants who received antibiotics for UC or gastrointestinal infection within 4 weeks prior to screening.
• Participants who have taken other investigational medications within 2 months or 5 half--lives, (whichever is longer) prior to screening.
• Presence of significant laboratory findings at the Screening Visit. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Colitis
• Colitis Ulcerative
• Colitis, Ulcerative
• Ulcer

Intervention

Drug:
• SAR443122
oral capsule
• Placebo
oral capsule

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320002	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320001	San Miguel de Tucuman
Chile	Investigational Site Number : 1520001	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520005	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520004	Talcahuano
China	Investigational Site Number : 1560001	Guangzhou
China	Investigational Site Number : 1560002	Shenyang
Czechia	Investigational Site Number : 2030001	Hradec Kralove
Czechia	Investigational Site Number : 2030002	Klatovy
Czechia	Investigational Site Number : 2030003	Praha
Czechia	Investigational Site Number : 2030004	Praha
France	Investigational Site Number : 2500006	Neuilly Sur Seine
France	Investigational Site Number : 2500001	Vandoeuvre-les-nancy
Germany	Investigational Site Number : 2760001	Kiel
Germany	Investigational Site Number : 2760006	Ulm
Hungary	Investigational Site Number : 3480002	Budapest
Hungary	Investigational Site Number : 3480003	Budapest
Hungary	Investigational Site Number : 3480005	Budapest
Hungary	Investigational Site Number : 3480006	Gyöngyös
India	Investigational Site Number : 3560003	Gurgaon
India	Investigational Site Number : 3560001	Jaipur
India	Investigational Site Number : 3560005	Kochi
India	Investigational Site Number : 3560004	Ludhiana
India	Investigational Site Number : 3560007	Pune
India	Investigational Site Number : 3560008	Rajkot
India	Investigational Site Number : 3560006	Thiruvananthapuram
Italy	Investigational Site Number : 3800004	Catanzaro
Italy	Investigational Site Number : 3800003	Milano
Italy	Investigational Site Number : 3800001	Pavia
Italy	Investigational Site Number : 3800002	Roma
Japan	Investigational Site Number : 3920002	Fukuyama-shi	Hiroshima
Japan	Investigational Site Number : 3920004	Kokuraminami-ku Kitakyushu-shi	Fukuoka
Japan	Investigational Site Number : 3920001	Oita-shi	Oita
Japan	Investigational Site Number : 3920003	Osaka-shi	Osaka
Mexico	Investigational Site Number : 4840003	Chihahua	Chihuahua
Mexico	Investigational Site Number : 4840001	Chihuahua
Mexico	Investigational Site Number : 4840002	Durango
Netherlands	Investigational Site Number : 5280001	Amsterdam
Netherlands	Investigational Site Number : 5280002	Nijmegen
Poland	Investigational Site Number : 6160009	Katowice
Poland	Investigational Site Number : 6160010	Leczna	Lubuskie
Poland	Investigational Site Number : 6160005	Pulawy	Lubuskie
Poland	Investigational Site Number : 6160002	Warszawa	Mazowieckie
Spain	Investigational Site Number : 7240001	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240005	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240002	Valencia	Valenciana, Comunidad
United Kingdom	Investigational Site Number : 8260002	Cambridge	Cambridgeshire
United Kingdom	Investigational Site Number : 8260006	London	London, City Of
United Kingdom	Investigational Site Number : 8260003	Warrington
United States	NY Scientific Site Number : 8400013	Brooklyn	New York
United States	Gastro One Site Number : 8400002	Cordova	Tennessee
United States	Om Research Site Number : 8400014	Lancaster	California
United States	Las Vegas Medical Research Site Number : 8400004	Las Vegas	Nevada
United States	Gastrointestinal Bioscience Site Number : 8400006	Los Angeles	California
United States	GI Alliance Research Site Number : 8400010	Mansfield	Texas
United States	Southern Star Research Site Number : 8400011	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Chile,  China,  Czechia,  France,  Germany,  Hungary,  India,  Italy,  Japan,  Mexico,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At Week 12
Secondary	Proportion of participants who achieve endoscopic improvement at Week 12		At Week 12
Secondary	Proportion of participants who achieve clinical response at Week 12 by mMS		At Week 12
Secondary	Proportion of participants who achieve clinical remission at Week 12 by full Mayo Score (MS)		At Week 12
Secondary	Proportion of participants who achieve clinical response at Week 12 by MS.		At Week 12
Secondary	Change from baseline on patient-reported outcome 2 (PRO2) total score (Mayo stool frequency and rectal bleeding subscores) over time		From baseline to Week 12
Secondary	Proportion of participants who achieve histological improvement at Week 12		At Week 12
Secondary	Proportion of participants who achieve Histologic-endoscopic mucosal improvement (HEMI) at Week 12 defined by achievement of modified Mayo endoscopic improvement and histological improvement		At Week 12
Secondary	Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score at Week 12		At Week 12
Secondary	Change from baseline in bowel signs and symptoms assessed by Ulcerative Colitis Patient Reported Outcome Signs and Symptoms (UC-PRO/SS) at Week 12		At Week 12
Secondary	Change from baseline in abdominal signs and symptoms assessed by UC-PRO/SS at Week 12		At Week 12
Secondary	Pharmacokinetic parameters: maximum concentration [Cmax]		Until Week 52
Secondary	Pharmacokinetic parameters: time to Cmax [tmax]		Until Week 52
Secondary	Pharmacokinetic parameters: area under the curve over the dosing interval [AUC0-tau]		Until Week 52
Secondary	Pharmacokinetic parameters: elimination half-life [t1/2z]		Until Week 52
Secondary	Participants with any Treatment Emergent Adverse Events (TEAEs) during induction and maintenance treatment period		Until Week 52
Secondary	Participants with any TEAEs during open-label treatment period		Up to Week 52

External Links

•   DRI16804 Ulcerative Colitis website