A study to investigate efficacy and safety of SAR441566 in patients with Crohn's disease

JRCT ID: jRCT2011240067

Registered date:22/01/2025

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Crohn's disease
• Date of first enrollment: 01/02/2025
• Target sample size: 260
• Countries of recruitment: Australia,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

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

Study Arms:
- Experimental: SAR441566 dose 1
Participants will receive SAR441566 dose 1.
- Experimental: SAR441566 dose 2
Participants will receive SAR441566 dose 2.
- Experimental: SAR441566 dose 3
Participants will receive SAR441566 dose 3.
- Placebo Comparator: Placebo
Participants will receive SAR441566 matching placebo.

Outcome(s)

Primary Outcome

1. Proportion of participants achieving endoscopic response
[Time Frame: Week 12]
Endoscopic response is defined as >=50% reduction from baseline in centrally read SES-CD.
The SES-CD evaluates 4 endoscopic variables (ulcer size, ulcerated surface, affected surface, and narrowing), each on a scale from 0 (none) to 3 in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and ranges from 0 to 56, where higher scores indicate more severe disease.

Secondary Outcome

1. Proportion of participants achieving clinical remission based on CDAI
[Time Frame: Week 12]
CDAI clinical remission is defined as CDAI score <150.
CDAI is a composite instrument that includes participant symptoms evaluated over 7 days (AP, SF, and general well-being), as well as presence of complications (arthritis/arthralgia, iritis/uveitis, erythema nodosum/pyoderma gangrenosum/aphthous stomatitis, anal fissure/fistula/abscess, other fistula, and fever), the use of antidiarrheal medicines, presence of an abdominal mass, hematocrit, and body weight. These items are scored individually, weighted, and do not contribute equally to the overall score. The CDAI is derived from summing up the weighted individual scores of eight items. CDAI approximately ranges from 0 to 600 with higher scores indicating more severe disease.
2. Proportion of participants achieving Patient-Reported Outcome (PRO-2) remission
[Time Frame: Week 12]
PRO-2 remission is defined as the unweighted CDAI component of daily AP score <=1, and the unweighted CDAI component of daily average SF score <=3 (ie, AP <=1 and SF <=3) and no worsening from baseline.
3. Proportion of participants achieving both clinical remission and endoscopic response
[Time Frame: Week 12]
Clinical remission and endoscopic response based on CDAI <150 and >=50% reduction from baseline in centrally read SES-CD.
4. Proportion of participants achieving endoscopic remission based on centrally read SES-CD
[Time Frame: From Baseline to Week 12]
Endoscopic remission is defined as a centrally read SES-CD <=4 points (SES-CD <=2 points for isolated ileal disease) and a SES-CD decrease from baseline >=2 points with no SES-CD sub score >1 point.
5. Proportion of participants achieving CDAI clinical response
[Time Frame: From Baseline to Week 12]
CDAI clinical response is defined as a CDAI reduction from baseline >=100 points.
6. Proportion of participants achieving Inflammatory Bowel Disease Questionnaire (IBDQ) remission
[Time Frame: Week 12]
IBDQ remission is defined as IBDQ total score >=170 points.
The IBDQ is used to assess health-related quality of life (HRQoL) in patients with inflammatory bowel disease. It consists of 32 questions evaluating bowel and systemic symptoms, as well as emotional and social functions. Each question is answered on a scale from 1 (worst) to 7 (best). The total score ranges from 32 to 224 with higher scores indicating better HRQoL.
7. Proportion of participants achieving IBDQ response
[Time Frame: From baseline to Week 12]
IBDQ response defined as an improvement of IBDQ scores by 27 points or more at Week 12 compared with baseline.
8. Change from baseline in the IBDQ scores
[Time Frame: From Baseline to Week 12]
The total IBDQ score ranges from 32 to 224 which indicates better HRQoL. A positive change from baseline indicates improvement.
9. Plasma pre-dose concentrations of SAR441566 at selected visits
[Time Frame: Up to Week 104]
10. Plasma post-dose concentrations of SAR441566 at selected visits
[Time Frame: Up to Week 104]
11. Number of participants experiencing any treatment-emergent adverse events (TEAEs)
[Time Frame: Up to Week 52]
Any TEAEs, including any serious opportunistic infections, psoriasiform skin lesions or other immune mediated phenomena during double-blind (DB) induction and maintenance treatment period.
12. Number of participants experiencing any TEAEs
[Time Frame: From Week 12 to Week 104]
Any TEAEs, including any serious opportunistic infections, psoriasiform skin lesions or other immune mediated phenomena during double-blind maintenance extension (DBME) and open-label (OL) treatment periods.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 75age old
• Gender: Both

Include 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 informed consent form.
- Confirmed diagnosis of Crohn's disease (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 (steroids, immunomodulators or antibiotics) or advanced therapies (biologics or small molecules), but having inadequate response to, loss of response to or intolerance to at least one of these therapies.
- On stable doses of standard treatments prior to screening (Oral 5-aminosalicylate [5-ASA] compounds, Oral corticosteroids, Azathioprine [AZA], 6-mercaptopurine [6-MP], or Methotrexate [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.

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
- Participants with active ulcerative colitis (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 TB or undergoing treatment for 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.
- Participants with adenomatous colonic polyps or colonic mucosal dysplasia (low- or high grade) not excised or incompletely excised.
- Infection(s) requiring treatment with intravenous (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.

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT06637631,2024-512633-32-00