A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, Clinical Activity, and Pharmacodynamic Effects of R-3750 in Patients With Crohn's Disease
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 40
- 主要终点
- Number of Adverse Events.
研究概览
简要总结
This is a multicenter, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, clinical activity, and pharmacodynamic effects of R-3750 in adults with active Crohn's disease. Approximately 40 participants will be randomized 1:1 to receive R-3750 or matching placebo orally once daily for 12 weeks. Participants will be followed for safety, clinical response, and durability of response through approximately Day 168. Assessments will include adverse events, Crohn's disease activity, endoscopic response, patient-reported outcomes, inflammatory biomarkers, microbiome composition, and pharmacodynamic measures.
详细描述
This is a multicenter, randomized, double-blind, placebo-controlled Phase 1 study designed to evaluate the safety, tolerability, clinical activity, and pharmacodynamic effects of R-3750 in adults with active Crohn's disease.
Approximately 40 participants will be randomized in a 1:1 ratio to receive either R-3750 at a dose of 9E10 colony-forming units (CFU) per day or matching placebo administered orally once daily for 12 weeks. Participants, investigators, study site personnel involved in outcome assessments, and Sponsor personnel involved in study conduct and assessment will remain blinded to treatment assignment.
Eligible participants will be adults 18 to 80 years of age with active Crohn's disease, defined by a Harvey-Bradshaw Index (HBI) score of 5 to 15 and objective evidence of active inflammatory disease based on C-reactive protein (CRP), fecal calprotectin, biopsy-verified inflammation, and/or endoscopic assessment.
The study consists of a screening period, a 12-week treatment period from Day 1 through Day 84, and a safety follow-up period through approximately Day 168.
Safety and tolerability will be evaluated through the assessment of adverse events and serious adverse events, clinical laboratory parameters, vital signs, and physical examinations. Clinical activity will be evaluated using measures including the Crohn's Disease Activity Index (CDAI) and HBI. Additional assessments will evaluate clinical remission, endoscopic response, patient-reported outcomes, inflammatory biomarkers, microbiome composition, immune phenotypes, metabolomic profiles, and other pharmacodynamic measures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 80 years, inclusive, at the time of informed consent.
- •Able and willing to provide written informed consent and comply with study procedures and study visits.
- •Documented diagnosis of Crohn's disease with symptoms/onset of disease at least 3 months prior to Screening.
- •Active Crohn's disease defined by Harvey-Bradshaw Index (HBI) score between 5 and 15 at Screening.
- •Evidence of active inflammatory disease, defined by at least one of the following: CRP ≥5 mg/L, fecal calprotectin ≥50 µg/g, biopsy-verified inflammation, or endoscopic evidence of active inflammation.
- •Women of childbearing potential must have a negative pregnancy test at Screening and before dosing and agree to use highly effective contraception during the study and for at least 3 months after the last dose.
- •Men with partners of childbearing potential must agree to use contraception according to institutional requirements during the study and for at least 3 months after the last dose.
排除标准
- •Crohn's disease in clinical remission, including HBI <5 or CDAI <150 at Screening.
- •Severe Crohn's disease requiring urgent escalation of therapy, hospitalization, or surgery in the opinion of the Investigator.
- •Imminent risk of scheduled intestinal surgery, including clinically significant stenosis, strictures, internal fistula, abscess, or obstructive complications.
- •History of partial or incomplete bowel obstruction within 6 months prior to Screening; current stoma, ileostomy, colostomy, or anticipated need for ostomy during the study; diagnosis of short bowel syndrome or clinically significant malabsorptive condition; uncontrolled chronic diarrhea due to a condition other than Crohn's disease; or bowel resection within 3 months prior to Screening.
- •Subjects with prior bowel resection may be eligible if, in the opinion of the Investigator and Sponsor, the remaining bowel anatomy is adequate for study participation and interpretation of study endpoints.
- •History (past 6 months) or current Clostridioides difficile infection, clinically significant enteric infection, other active infection or chronic infection requiring ongoing antimicrobial treatment.
- •Treatment with antibiotics within 2 weeks prior to Day 1 or expected during the study period.
- •Use of biologic, targeted synthetic, or systemic immunomodulatory/immunosuppressive therapy for Crohn's disease within the 4 weeks washout period prior to Day 1, unless specifically permitted. Stable doses of aminosalicylates, budesonide, or low-dose systemic corticosteroids are permitted if stable for at least 2 weeks prior to Day 1 and expected to remain stable during the treatment period. Low-dose systemic corticosteroids are defined as prednisone ≤20 mg/day or equivalent.
- •Use of probiotics or live biotherapeutic products within 2 weeks prior to Day
- •Severe comorbidities, including uncontrolled diabetes, clinically significant cardiopulmonary failure, severe liver disease, severe renal disease, or other clinically significant condition that would place the subject at risk or confound study interpretation.
- •Abnormal hepatic function, including ALT or ALP >2.5 × ULN, liver cirrhosis, portal hypertension, or clinically significant active liver disease.
- •Abnormal renal function, including cystatin C >ULN or other clinically significant renal abnormality.
- •Known active blood-borne infection, including HIV, active hepatitis A, B, or C infection, or tuberculosis.
- •History of malignancy within 5 years prior to Day 1, except adequately treated non-metastatic basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
- •Pregnant, breastfeeding, or planning to become pregnant during the study. Clinically significant mental disorder, substance use disorder, alcohol or drug addiction that may interfere with participation or compliance.
- •Participation in another interventional clinical trial within 30 days prior to Day 1 or simultaneous participation in another interventional clinical trial.
- •Any significant disease, disorder, laboratory abnormality, or circumstance that, in the opinion of the Investigator, may put the subject at risk, affect study results, or interfere with study participation.
研究组 & 干预措施
Arm 2: Matching placebo orally once daily for 12 weeks
Participants randomized to the placebo comparator arm will receive matching placebo administered orally once daily from Day 1 through Day 84 (12 weeks).
干预措施: Placebo (Drug)
Arm 1: R-3750, 9E10 CFU/day orally once daily for 12 weeks
Participants randomized to the experimental arm will receive R-3750 at a dose of 9E10 colony-forming units (CFU) per day, administered orally once daily from Day 1 through Day 84 (12 weeks).
干预措施: R-3750 (Drug)
结局指标
主要结局
Number of Adverse Events.
时间窗: From first dose through Day 168 end of study
Number of participants experiencing one or more treatment-emergent adverse events following administration of R-3750 or placebo.
次要结局
- Number of participants with serious adverse advents(From first dose through Day 168 end of study)