Dose-finding Study of SAR443122 in Adult Participants With Ulcerative Colitis
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|ClinicalTrials.gov Identifier: NCT05588843|
Recruitment Status : Recruiting
First Posted : October 20, 2022
Last Update Posted : January 23, 2023
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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.
|Condition or disease||Intervention/treatment||Phase|
|Colitis Ulcerative||Drug: SAR443122 Drug: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||182 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Actual Study Start Date :||November 25, 2022|
|Estimated Primary Completion Date :||June 19, 2025|
|Estimated Study Completion Date :||April 9, 2026|
Experimental: SAR443122 level 1
Dose level 1
Experimental: SAR443122 level 2
Dose level 2
Experimental: SAR443122 level 3
Dose level 3
Placebo Comparator: Placebo
- Proportion of participants who achieve clinical remission at Week 12 by modified Mayo Score (mMS) [ Time Frame: At Week 12 ]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.
- Proportion of participants who achieve endoscopic improvement at Week 12 [ Time Frame: At Week 12 ]
- Proportion of participants who achieve clinical response at Week 12 by mMS [ Time Frame: At Week 12 ]
- Proportion of participants who achieve clinical remission at Week 12 by full Mayo Score (MS) [ Time Frame: At Week 12 ]
- Proportion of participants who achieve clinical response at Week 12 by MS. [ Time Frame: At Week 12 ]
- Change from baseline on patient-reported outcome 2 (PRO2) total score (Mayo stool frequency and rectal bleeding subscores) over time [ Time Frame: From baseline to Week 12 ]
- Proportion of participants who achieve histological improvement at Week 12 [ Time Frame: At Week 12 ]
- Proportion of participants who achieve Histologic-endoscopic mucosal improvement (HEMI) at Week 12 defined by achievement of modified Mayo endoscopic improvement and histological improvement [ Time Frame: At Week 12 ]
- Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score at Week 12 [ Time Frame: At Week 12 ]
- Change from baseline in bowel signs and symptoms assessed by Ulcerative Colitis Patient Reported Outcome Signs and Symptoms (UC-PRO/SS) at Week 12 [ Time Frame: At Week 12 ]
- Change from baseline in abdominal signs and symptoms assessed by UC-PRO/SS at Week 12 [ Time Frame: At Week 12 ]
- Pharmacokinetic parameters: maximum concentration [Cmax] [ Time Frame: Until Week 52 ]
- Pharmacokinetic parameters: time to Cmax [tmax] [ Time Frame: Until Week 52 ]
- Pharmacokinetic parameters: area under the curve over the dosing interval [AUC0-tau] [ Time Frame: Until Week 52 ]
- Pharmacokinetic parameters: elimination half-life [t1/2z] [ Time Frame: Until Week 52 ]
- Participants with any Treatment Emergent Adverse Events (TEAEs) during induction and maintenance treatment period [ Time Frame: Until Week 52 ]
- Participants with any TEAEs during open-label treatment period [ Time Frame: Up to Week 52 ]
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|Ages Eligible for Study:||18 Years to 75 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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®).
- 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 biologics must have been administered 1) at least 5 half-lives prior to randomization, or 2) participant must have an 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.
- Participants with Crohn's Disease (CD).
- Participants with diagnosis of indeterminate colitis.
- Participants with stool sample positive for culture for aerobic pathogens.
- 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 malignancies except history of basal cell carcinoma or in-situ cervical carcinoma.
- 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 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
- 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 screening test suspected of 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.
- Participants under cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide or tacrolimus treatment within 4 weeks prior to screening.
- Participants with previous exposure to natalizumab (Tysabri®), JAK (Janus kinase) inhibitors or S1P receptor modulator.
- 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 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05588843
|Contact: Trial Transparency email recommended (Toll free number for US & Canada)||800-633-1610 ext option 6||Contact-US@sanofi.com|
|United States, California|
|United Medical Doctors-Site Number:8400005||Recruiting|
|Los Alamitos, California, United States, 90720|
|United States, Nevada|
|Las Vegas Medical Research-Site Number:8400004||Not yet recruiting|
|Las Vegas, Nevada, United States, 89113|
|United States, North Carolina|
|Onsite Clinical Solutions-Site Number:8400003||Recruiting|
|Salisbury, North Carolina, United States, 28144|
|Investigational Site Number :0320001||Recruiting|
|San Miguel de Tucuman, Tucumán, Argentina, T4000AXL|
|Investigational Site Number :1520001||Recruiting|
|Santiago, Reg Metropolitana De Santiago, Chile, 7500010|
|Investigational Site Number :8260003||Recruiting|
|Warrington, United Kingdom, WA5 1QG|
|Other Study ID Numbers:||
U1111-1269-6212 ( Registry Identifier: ICTRP )
2022-500290-14-01 ( Other Identifier: EMA )
|First Posted:||October 20, 2022 Key Record Dates|
|Last Update Posted:||January 23, 2023|
|Last Verified:||January 21, 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Digestive System Diseases
Inflammatory Bowel Diseases