A Study to Investigate Efficacy and Safety of SAR441566 in Patients With Crohn's Disease.

Official title

A Phase 2, Multinational, Multicenter, Randomized, Doubleblind, Placebocontrolled, Dose-ranging Study to Evaluate the Efficacy and Safety of SAR441566 in Adults With Moderate to Severe Crohn's Disease.

Overview

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 Crohn's Disease (CD). The primary objective of this study is to assess the efficacy of different doses of SAR441566 compared with placebo in participants with moderate to severe CD. This study will have an anticipated duration of up to 59 weeks which will include a screening period of 4 weeks (+7 calendar days if needed), followed by the Main Study (MS) treatment period, lasting 52 weeks, and a 2-week follow-up period after end of treatment for participants not enrolling in the Long Term Safety (LTS) study. The MS period includes a Double-Blind (DB) treatment period with 12 weeks of induction followed by 40 weeks of maintenance. Additionally, an Open Label (OL) period of up to 40 weeks will be offered to eligible participants. The combined duration of the DB maintenance and OL periods cannot exceed 40 weeks, depending on when participants switch.

Interventions

• Drug SAR441566
  Pharmaceutical form: Tablet Route of administration: Oral
• Drug SAR441566 matching Placebo
  Pharmaceutical form: Tablet Route of administration: Oral

Primary outcome measures

• Proportion of participants achieving endoscopic response [Time frame: Week 12]

Secondary outcome measures (12)

• Proportion of participants achieving clinical remission based on Crohn's Disease Activity Index (CDAI) [Time frame: Week 12]
• Proportion of participants achieving Patient-Reported Outcome (PRO-2) remission [Time frame: Week 12]
• Proportion of participants achieving both clinical remission and endoscopic response [Time frame: Week 12]
• Proportion of participants achieving endoscopic remission based on centrally read SES-CD [Time frame: From Baseline to Week 12]
• Proportion of participants achieving CDAI clinical response [Time frame: From Baseline to Week 12]
• Proportion of participants achieving Inflammatory Bowel Disease Questionnaire (IBDQ) remission [Time frame: Week 12]
• Proportion of participants achieving IBDQ response [Time frame: From baseline to Week 12]
• Change from baseline in the IBDQ scores [Time frame: From Baseline to week 12]
• Plasma pre-dose concentrations of SAR441566 at selected visits [Time frame: Up to week 52]
• Plasma post-dose concentrations of SAR441566 at selected visits [Time frame: Up to week 52]
• Number of participants experiencing any TEAEs [Time frame: Up to week 52]
• Number of participants experiencing any TEAEs [Time frame: From week 12 to week 52]

Eligibility criteria

Inclusion criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

• Male or female participants aged 18 to 75 years at the time of signing the ICF
• Confirmed diagnosis of CD for at least 3 months prior to Baseline
• Confirmed diagnosis of moderate to severe CD as assessed by:

• Crohn's Disease Activity Index (CDAI) score and the Simple Endoscopic Score for Crohn's disease (SES-CD) on an endoscopy confirmed by a central reader
• stool frequency (SF), abdominal pain (AP) score
• History of prior exposure to standard treatment (5-ASA, steroids, immunomodulators or antibiotics) or advanced therapies (biologics or small molecules), but having inadequate response to, loss or response to or intolerance to at least one of these therapies
• On stable doses of standard treatments prior to screening (oral 5-ASA compounds, oral corticosteroids, thiopurines (eg. AZA, 6-MP), or MTX)
• 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 are excluded from the study if any of the following criteria apply:

• Participants with active UC, indeterminate colitis or short bowel syndrome
• Participants with CD isolated to the stomach, duodenum, jejunum, or peri anal region, without colonic or ileal involvement
• Participants with following ongoing known complications of CD: fistula, abscess, symptomatic stricture/stenosis, fulminant colitis, toxic megacolon, recent bowel resection within 3 months of screening or history of > 3 bowel resections
• Participants with stool sample positive for infectious pathogens
• Participants with active tuberculosis (TB) or a history of incompletely treated active or latent TB per local guidelines
• 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 with any other active, chronic or recurrent infection, including recurrent or disseminated herpes zoster or disseminated herpes simplex
• Participants with a known history of Human Immunodeficiency Virus (HIV) infection or positive HIV-1 or HIV-2 serology at screening
• Participants presenting with active malignancies, lymphoproliferative disease, or recurrence of either, within the 5 years before screening
• History of colonic mucosal dysplasia or presence of colonic mucosal dysplasia or adenomatous colonic polyps not removed during colonoscopy at screening visit
• Infection(s) requiring treatment with IV anti infectives within 30 days or oral/intramuscular anti-infectives within 14 days prior to the screening visit
• Participants requiring or receiving any parental nutrition and/or exclusive enteral nutrition
• Participants who received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to screening
• Participants who received fecal microbial transplantation within 30 days prior to screening
• Participants who have ever been exposed to natalizumab (Tysabri®) or oral carotegrast methyl (Carogra®)
• Participants who received IV corticosteroids within 14 days prior to screening or during screening period
• Participants who received therapeutic enema or suppository, other than required for colonoscopy within 14 days prior to screening or during screening
• Screening laboratory and other analyses show abnormal results

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 19 centers

• GI Alliance - Arizona Digestive Health - Sun City- Site Number : 8400020 — Sun City
• Bristol Hospital- Site Number : 8400007 — Bristol
• Novum Research- Site Number : 8400021 — Clermont
• Homestead Associates in Research- Site Number : 8400012 — Homestead
• Clinical Research of Osceola- Site Number : 8400013 — Kissimmee
• Wellness Clinical Research - Miami Lakes - 8181 Northwest 154th Street- Site Number : 8400 — Miami Lakes
• GCP Clinical Research- Site Number : 8400004 — Tampa
• GI Alliance - Glenview- Site Number : 8400015 — Glenview
• … and 11 more centers

Japan · 14 centers

Center list to be confirmed — check the primary protocol.

China · 12 centers

• Investigational Site Number : 1560008 — Changzhou
• Investigational Site Number : 1560009 — Chongqing
• Investigational Site Number : 1560012 — Fuzhou
• Investigational Site Number : 1560001 — Guangzhou
• Investigational Site Number : 1560002 — Guangzhou
• Investigational Site Number : 1560004 — Hangzhou
• Investigational Site Number : 1560003 — Hangzhou
• Investigational Site Number : 1560007 — Hefei
• … and 4 more centers

India · 9 centers

Center list to be confirmed — check the primary protocol.

Hungary · 8 centers

Center list to be confirmed — check the primary protocol.

Georgia · 7 centers

• Investigational Site Number : 2680006 — Kutaisi
• Investigational Site Number : 2680007 — Tbilisi
• Investigational Site Number : 2680001 — Tbilisi
• Investigational Site Number : 2680005 — Tbilisi
• Investigational Site Number : 2680002 — Tbilisi
• Investigational Site Number : 2680003 — Tbilisi
• Investigational Site Number : 2680004 — Tbilisi

Italy · 7 centers

Center list to be confirmed — check the primary protocol.

Argentina · 6 centers

• Investigational Site Number : 0320002 — San Miguel de Tucumán
• Investigational Site Number : 0320003 — Buenos Aires
• Investigational Site Number : 0320005 — Buenos Aires
• Investigational Site Number : 0320001 — Buenos Aires
• Investigational Site Number : 0320004 — Buenos Aires
• Investigational Site Number : 0320006 — Buenos Aires

Chile · 6 centers

• Investigational Site Number : 1520006 — Concepción
• Investigational Site Number : 1520004 — Talcahuano
• Investigational Site Number : 1520007 — Temuco
• Investigational Site Number : 1520001 — Santiago
• Investigational Site Number : 1520003 — Santiago
• Investigational Site Number : 1520002 — Viña del Mar

Brazil · 5 centers

• Centro de Pesquisas da Clínica IBIS- Site Number : 0760001 — Salvador
• Hospital Moinhos de Vento- Site Number : 0760006 — Porto Alegre
• Hospital de Clinicas de Porto Alegre- Site Number : 0760007 — Porto Alegre
• Hospital Ernesto Dornelles- Site Number : 0760002 — Porto Alegre
• Pesquisare Saude- Site Number : 0760004 — Santo André

France · 5 centers

• Investigational Site Number : 2500005 — Montpellier
• Investigational Site Number : 2500002 — Nice
• Investigational Site Number : 2500004 — Saint-Priest-en-Jarez
• Investigational Site Number : 2500003 — Toulouse
• Investigational Site Number : 2500001 — Vandœuvre-lès-Nancy

Germany · 5 centers

• Investigational Site Number : 2760004 — Berlin
• Investigational Site Number : 2760002 — Berlin
• Investigational Site Number : 2760001 — Fulda
• Investigational Site Number : 2760005 — Halle
• Investigational Site Number : 2760006 — Ludwigshafen

Poland · 5 centers

Center list to be confirmed — check the primary protocol.

Czechia · 4 centers

• Investigational Site Number : 2030003 — Brno
• Investigational Site Number : 2030002 — Brno
• Investigational Site Number : 2030004 — Hradec Králové
• Investigational Site Number : 2030006 — Prague

Netherlands · 4 centers

Center list to be confirmed — check the primary protocol.

Australia · 3 centers

• Investigational Site Number : 0360002 — Sydney
• Investigational Site Number : 0360001 — South Brisbane
• Investigational Site Number : 0360003 — Parkville

Bulgaria · 3 centers

• Investigational Site Number : 1000001 — Gorna Oryahovitsa
• Investigational Site Number : 1000004 — Sofia
• Investigational Site Number : 1000005 — Sofia

Canada · 3 centers

• Investigational Site Number : 1240001 — Calgary
• Investigational Site Number : 1240003 — Montreal
• Investigational Site Number : 1240005 — Québec

Romania · 3 centers

Center list to be confirmed — check the primary protocol.

South Korea · 3 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 3 centers

Center list to be confirmed — check the primary protocol.

Croatia · 2 centers

• Investigational Site Number : 1910004 — Osijek
• Investigational Site Number : 1910003 — Zagreb

Spain · 2 centers

Center list to be confirmed — check the primary protocol.

Mauritius · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06637631 · DRI18212 · 2024-512633-32-00 · U1111-1301-3830

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗