CTRI/2025/07/090083尚未招募2 期
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 Crohns disease
Sanofi Healthcare India Pvt Limited (SHIPL)8 个研究点 分布在 1 个国家目标入组 260 人开始时间: 2025年7月28日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 260
- 试验地点
- 8
- 主要终点
- - To assess efficacy and dose response of different doses of SAR441566 on endoscopic response at the end of induction treatment in participants with moderate to severe CD
研究概览
简要总结
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 CD. The target population of the study is participants with moderate to severely active CD, defined as active disease for at least 3 months prior to screening. Participants must have a Crohns Disease Activity Index (CDAI) score of 220 to 450 with an average daily very soft or liquid stool frequency (SF) more than equal to 4.0 and/or average daily abdominal pain (AP) score more than equal to 2.0 at screening. Participants must also have an endoscopic severity score for CD (Simple Endoscopic Score for Crohnss Disease (SES-CD)), excluding the presence of narrowing component) more than equal to 6 (or more than equal to 4 for participants with isolated ileal disease), as confirmed by a central reader. Participants on stable doses of standard therapies are eligible for the study. Standard therapies include oral steroids, thiopurines (azathioprine [AZA] or 6-mercaptopurine [6-MP]), methotrexate (MTX), or antibiotics (except medications prohibited due to the risk of drug-drug interaction [DDI] or knownrisk of Torsade de Pointes [TdP] Section 6.9 and Table 6, respectively). Although 5-aminosalicylates (5-ASAs) are not endorsed by many Gastroenterologic Societies as standard therapy for inducing or maintaining remission in moderate to severe CD (8, 9, 10), and 5-ASAs continue to be utilized in many countries for symptomatic control of CD. Participants on stable doses of 5-ASAs, therefore, would be eligible for the study. Participants who do not meet the inclusion criteria or meet one of the exclusion criteria will not be enrolled. Study Periods The study will consist of the following periods--
- Screening period of 4 weeks (+7 calendar days if needed);
- Main study (MS) treatment period of 52 weeks which will be comprised of a double-blind (DB) period with 12 weeks of induction period followed by 40 weeks of maintenance period; • Double-blind maintenance extension (DBME) treatment period of up to 52 weeks for eligible participants;
- Open label (OL) treatment period where eligible participants who clinically worsen at any time after completing 12 weeks of DB induction will be eligible to switch for up to 92 weeks;
2-week follow-up period after end of treatment (EOT). This study will use a “treat-through” design where participants at the end of the induction period continue into the maintenance period while remaining on the treatment arms to which they were originally randomized. This design more closely mimics the management of patients in real-world clinical practice and also allows the evaluation of the durability and safety of continuous treatment with SAR441566 during the MS period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Male or female participants aged 18 to 75 years at the time of signing the ICF. Type of participant and disease characteristics I
- •Participants with confirmed diagnosis of CD for at least 3 months prior to screening. Appropriate documentation of endoscopy, radiology andor biopsy (histology) results consistent with the diagnosis of CD, as determined by the Investigator, must be available whenever possible. I
- •Participants with moderate to severely active CD, defined as- active disease with a CDAI score of 220 to 450, with endoscopic SES-CD score (excluding the presence of narrowing component) more than equal to 6 (or more than equal to 4 for participants with isolated ileal disease), as confirmed by a central reader AND average daily very soft or liquid SF more than equal to 4.0 and/or average daily AP score more than equal to 2.0 at screening. Prior Treatment I
- •Must have received prior treatment for CD (either “a” or “b” below or a combination of both "a" and "b"): a) history of no prior exposure to approved AT (AT being defined as any biologic, JAKi or S1PRm) but having inadequate response to, loss of response to or intolerance to standard treatment with any of the following compounds: 6-MP, AZA, MTX, oral or intravenous (IV) corticosteroids or history of corticosteroid dependence (defined an inability to successfully taper corticosteroids without recurrence of CD) OR b) history of inadequate response to, loss of response to, or intolerance to, treatment with one or more approved AT(s) where AT is a biologic agent for CD (eg, TNF antagonists, anti-integrin, anti-IL-12/23, anti-IL-23, or experimental biologic CD therapeutics) ora small molecule (such as JAKi or S1PRm). The treatment must have been discontinued according to the following timeline:.
- •Treatment with a TNF antagonist, vedolizumab, ustekinumab or rizankizumab at least 8 weeks before randomization.
- •Experimental CD therapy at least 8 weeks before randomization (for biologics) or 5 times the terminal half-lives of the investigational drug, whichever is longer. I
- •Participant may be receiving a therapeutic dosage of the following drugs-.
- •Oral 5-ASA compounds- prescribed dose must be stable for at least 2 weeks before screening colonoscopy or stopped treatment at least 2 weeks prior to screening colonoscopy.
- •Oral corticosteroids must be at a prednisone-equivalent dose of less than equal to 20 mg/day, or less than equal to 9 mg/day of budesonide, and have been at a stable dose for at least 2 weeks prior to the screening colonoscopy or stopped at least 2 weeks prior to screening colonoscopy.
- •AZA, 6-MP, or MTX: if the prescribed dose has been stable for at least 4 weeks before screening colonoscopy, or, if stopped, medication must have been discontinued for at least 4 weeks prior to screening colonoscopy to be considered eligible for enrollment.
- •Antibiotics (except those that may be QTc prolonging) prescribed at doses that have been stable for at least 4 weeks before screening colonoscopy, or if stopped, medication must have been discontinued at least 4 weeks prior to screening colonoscopy to be considered eligible for enrollment. Sex, contraceptive/barrier method and pregnancy testing requirements/breastfeeding. I
- •Male participants who are sexually active with female partner(s) of childbearing potential must agree to practice the protocol-specified contraception during the study and for up to 3 months, after the last dose of IMP which will allow for one complete cycle of spermatogenesis following study drug discontinuation. Males must refrain from donating sperm during the study treatment period and for up to 3 months after the last dose of IMP. I
- •Female participants.
- •A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies- Is a woman of non-child-bearing potential as defined in the Section 10.4; OR.
- •Is a WOCBP and agrees to use a contraceptive method that is highly effective (with a failure rate of f less than 1percent per year), preferably with low user dependency (as described in Section 10.4) during the study intervention period (to be effective before starting IMP) and for at least 3 months after the last administration of study IMP and agrees not to donate or cryopreserve eggs (ova, oocytes) for the purpose of reproduction during this period.
- •A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) at screening and a negative urine pregnancy test before the first administration of study IMP. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. I
- •WOCBP potential may participate and include those who are: infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as Müllerian agenesis; or post-menopausal – defined as either: -- a woman at least 50 years of age with an intact uterus, not on hormone therapy, who has had either:.
- •cessation of menses for at least 1 year, or.
- •at least 6 months of spontaneous amenorrhea with a follicle-stimulating hormone more than 40 mIU/mL, or -- a woman more than equal to 55 years of age not on hormone therapy, who has had at least 6 months of spontaneous amenorrhea; or -- a woman at least 55 years of age with a diagnosis of menopause prior to starting hormone replacement therapy. Informed Consent I
- •Willing to participate, able to provide written ICF and be compliant with the schedule of protocol assessments. In countries where legal age of majority is above 18 years, a specific ICF must also be signed by the participant’s legally authorized representative.
排除标准
- •EXCLUSION CRITERIA Participants are excluded from the study if any of the following criteria apply: Medical conditions E
- •Participants with active UC, indeterminate colitis or short bowel syndrome. E
- •Participants with CD isolated to the stomach, duodenum, jejunum, or peri-anal region, without colonic or ileal involvement. E
- •Participants with following ongoing known complications of CD -Fistulizing disease -Abscess (abdominal or peri anal) -Symptomatic bowel strictures -Two entire missing segments (either surgically removed or not visible during most recent colonoscopy) of the following five segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum -Fulminant colitis -Toxic megacolon -Or any other manifestation that might require bowel surgery while enrolled in the study -Participant with ostomy or ileoanal pouch -Participant diagnosed with conditions that could interfere with drug absorption including but not limited to short bowel syndrome -Participant with surgical bowel resection within the past three months prior to screening, or a history of more than 3 bowel resections E
- •Participant with a gastrointestinal infection, as indicated by a positive stool culture at screening for aerobic pathogens (including Aeromonas, Plesiomonas, Shigella, Salmonella, Yersinia, Campylobacter, or E. coli spp), a positive ova and parasite stool evaluation, or a positive Clostridium difficile B toxin in stools. E
- •At screening visit, participants with positive -Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody immunoglobulin M (HBcAb IgM), or HBc Ab total -Hepatitis C virus antibody (HCVAb) confirmed by positive by positive hepatitis C virus-deoxyribonucleic (HCV RNA) (participants with HCVAb and negative HCV RNA who have documented evidence of completing HCV anti-viral with cure may be included) -Any other active, chronic or recurrent infection, including recurrent or disseminated herpes zoster or disseminated herpes simplex E
- •Participants with a known history of Human Immunodeficiency Virus (HIV) infection or positive HIV-1 or HIV-2 serology at screening. E
- •Participants with active TB or who meet TB exclusionary parameters: -Active TB or a history of incompletely treated TB -Undergoing treatment of latent TB infection (LTBI) -Positive QuantiFERON -TB test at screening. Indeterminate QuantiFERON -TB may be repeated once during screening period and will be considered positive if retest results positive or indeterminate -Current household contacts with active TB -Received Bacillus Calmette-Guérin vaccination within 12 months prior to screening -Participants meeting all the following TB-related criteria would not excluded: ---Documented completed appropriate LTBI treatment, or treated for active TB infection (with a treatment regimen as per local guidelines),.
- •Have obtained consultation with specialist to rule out or treat active TB infection --- For whom review and approval from Sponsor have been granted are eligible Note: TB testing is mandatory to rule out active/latent TB and a blood sample for QuantiFERON Tuberculosis Gold Interferon ---Gamma Release Assay testing should be sent to the central laboratory. E
- •Participants presenting with active malignancies, lymphoproliferative disease, or recurrence of either, within the 5 years before screening (with the exception of the following treated malignancies that are allowed in the study: basal cell carcinoma, adequately squamous cell carcinoma in situ of the skin or cervical carcinoma in situ). E
- •Participants with adenomatous colonic polyps or colonic mucosal dysplasia (low- or high-grade) not excised or incompletely excised. E
- •Participants with active diverticulitis, history of GI perforation (other than appendicitis or mechanical injury), or significantly increased risk for GI perforation per Investigators judgment. E
- •Female participant who is pregnant, breastfeeding, or is considering becoming pregnant during the study or within 30 days after the last dose of IMP. E
- •Participants with a history of allergic reaction or significant sensitivity to components of the IMP (and its excipients). E
- •Participants with any of the following cardiovascular conditions or thrombotic conditions at screening:.
- •Participants with New York Heart Association Class III or higher heart failure.
- •Participants with recent (within past 6 months before screening) cerebrovascular accident, myocardial infarction, or coronary stenting;.
- •Participants with current uncontrolled hypertension as defined by a confirmed systolic blood pressure (BP) more than 160 mmHg or diastolic BP more than100 mmHg.
- •Participants with known inherited conditions that predispose to hypercoagulability E
- •History of diagnosis of demyelinating disease such as but not limited to: -Multiple Sclerosis.
- •Acute Disseminated Encephalomyelitis.
- •Balos Disease (Concentric Sclerosis).
- •Charcot-Marie-Tooth Disease.
- •Guillain-Barre Syndrome.
- •Human T-lymphotropic virus 1 Associated Myelopathy.
- •Neuromyelitis Optica (Devics Disease) OR.
- •any other clinically significant medical condition(s) or any other reason that in the opinion of the Investigator would interfere with the participant; s participation in this study or would make the participant an unsuitable candidate to receive IMP or would put the participant at risk by participating in the study E
- •Participants who have received vaccination with live or live-attenuated virus vaccine(s) within 3 months prior to screening or have an expected need of live vaccination during study participation including at least 12 weeks after the last dose of IMP Prior/concomitant therapy E
- •Participants with usage of below prior/concomitant medications.
- •Use of strong CYP3A4 inhibitors or strong CYP3A4 inducers within 7 days (for inhibitors) and 14 days (for inducers), respectively, or 5 times the elimination half-life of the medication (whichever is longer) prior to the first IMP administration, or the need for ongoing treatment with concomitant oral or intravenous therapy with strong CYP3A4 inhibitors or strong CYP3A4 inducers during the screening. See Table 16 and Table 15 for a list of medications that are CYP3A4 inhibitors and inducers, respectively.
- •Use of P-gp inhibitors or inducers which clinically alter the systemic exposure of the victim drug by at least 2-fold within 7 days (for inhibitors) and 14 days (for inducers), respectively, prior to start of IMP administration or within 5 times the elimination half-life of the medication whichever is the longer, or the need for ongoing treatment with these P-gp inhibitors or inducers during the screening. See Table 17 and Table 18 for a list of medications that are P-gp inhibitors and inducers, respectively.
- •Use of P-gp substrates with a narrow therapeutic index, for which the label indicates that P-gp inhibition led to an increase in systemic exposure, within 7 days prior to start of IMP administration or within 5 times the elimination half-life of the medication (whichever is the longer) or the need for ongoing treatment with these substrates during the screening. See Section 6.9.2 for a list of medications that are P-gp substrates with a narrow therapeutic index.
- •Sensitive CYP1A2 substates with a narrow therapeutic index within 7 days prior start of IMP administration or 5 time the elimination half-life of the medication whichever is the longer, or the need for ongoing treatment with concomitant oral or IV therapy with these drugs during the screening. See Section 6.9.2 for a list of medications that are CYP1A2 substrates with a narrow therapeutic index. E
- •Use of any opiates or other anti-diarrheal medications is prohibited during screening. See Table 6 for a list of these medications. E
- •The use of concomitant medications that prolong the QT/QTc interval with known risk of TdP (Table 19). E
- •Infection(s) requiring treatment with IV anti-infectives within 30 days prior to the screening visit or oral/intramuscular anti-infectives within 14 days prior to the screening visit. E
- •Participants requiring or receiving any parental nutrition and/or exclusive enteral nutrition. E
- •Participants who received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to screening. E
- •Participants who received fecal microbial transplantation within 30 days prior to screening. E
- •Participants who have ever been exposed to 4 or more marketed ATs including biologics or small molecules (JAKi or S1PRm) during their lifetime. Exposure is defined as having received one complete dose of the AT. E
- •Participants who have ever been exposed to natalizumab (Tysabri) or oral carotegrast methyl (Carogra), or exposed to any of the following agents:.
- •4 or more biologic anti-TNFs during their lifetime, or exposure to Adalimumab, certolizumab, golimumab, infliximab, or an anti-TNF biosimilar within 8 weeks prior to randomization.
- •Vedolizumab, ustekinumab, or rizankizumab within 8 weeks prior to randomization Note: If there is proper documentation of an undetectable drug level measured by a commercially available assay for any of the approved biologics above, there is no minimum washout prior to randomization. E
- •Participants with previous exposure to a JAKi (eg, tofacitinib, filgotinib, upadacitinib) within 2 weeks of the screening visit. Note: Participants who received a JAKi prior to study entry may be enrolled if they have not had inadequate response or loss of response. E
- •Participants who received IV corticosteroids within 14 days prior to screening or during screening period. E
- •Participants who received therapeutic enema(s) or suppository(ies) (eg, rectal 5-ASA/corticosteroids), other than required for colonoscopy, within 14 days prior to the colonoscopy used for screening or during the treatment. E
- •Participants who received apheresis (eg, adacolumn apheresis) within 60 days prior to screening or during screening period. E
- •Participants with cannabis use, either recreational or for medical reasons, within 14 days prior to screening visit or any history of clinically significant (as per Investigators judgement) drug or alcohol abuse in last six months. E
- •Participants who have previously received stem cell transplantation (except for local stem cell therapy for complex perianal fistula). E
- •Participants who have been the recipient of an organ transplant which requires continued immunosuppression. Prior/concurrent clinical study experience E
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结局指标
主要结局
- To assess efficacy and dose response of different doses of SAR441566 on endoscopic response at the end of induction treatment in participants with moderate to severe CD
时间窗: week 12
次要结局
- - To assess the effect of different doses of SAR441566 on clinical remission at the end of induction treatment in participants with moderate to severe CD.(week 12)
- - To assess the effect of different doses of SAR441566 on patient-reported outcomes (PRO)/signs and symptoms of CD at the end of induction treatment.(week 12)
- -To assess the effect of different doses of SAR441566 on the composite endpoint of clinical remission and endoscopic response at the end of induction treatment in participants with moderate to severe CD.(week 12)
- - To assess the effect of different doses of SAR441566 on endoscopic remission at the end of induction treatment in participants with moderate to severe CD.(week 12)
- - To assess the effect of different doses of SAR441566 on clinical response at the end of induction treatment in participants with moderate to severe CD.(week 12)
- - To assess the effect of different doses of SAR441566 on disease specific QOL at the end of induction treatment.(week 12)
- - To assess PK of different doses of SAR441566 in participants with moderate to severe CD(Week 12)
- - To assess the safety and tolerability of different doses of SAR441566 in participants with moderate to-severe CD(week 12)
研究者
研究点 (8)
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