Phase 2b/3, Randomized, Double Blind, Placebo Controlled Induction Phase Followed by a Maintenance Phase to Evaluate the Efficacy & Safety of ABX464 in Patients With Moderate to Severe Active Crohn's Disease & to Determine the Optimal Dose
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- Abivax S.A.
- 试验地点
- 1
- 主要终点
- The co-primary objectives of the study are to determine the efficacy of ABX464 in inducing clinical remission and endoscopic improvement after 12 weeks of study treatment in patients with moderate to severe active CD who have inadequate response, loss of
研究概览
简要总结
This is a multicenter, randomized, placebo controlled study to evaluate the efficacy and safety of ABX464, administered once daily (QD), in inducing clinical remission and endoscopic response in patients with moderate to severe active Crohn's disease (CD) who have inadequate response, loss of response, or intolerance to prior corticosteroid and/or immunosuppressant treatment and/or biologics. This study consists of a 28 day Screening Period, a 52 week Treatment Period; including a 12 week double blinded (Cohort 1) or open label (Cohort 2) Induction Phase and a 40 week double blinded (responders) or open label (nonresponders) Maintenance Phase; and a 4 week Follow up Period, which will consist of an End of Study (EOS) visit
详细描述
This is a multicenter, randomized, placebo controlled study to evaluate the efficacy and safety of ABX464, administered once daily (QD), in inducing clinical remission and endoscopic response in patients with moderate to severe active Crohn's disease (CD) who have inadequate response, loss of response, or intolerance to prior corticosteroid and/or immunosuppressant treatment and/or biologics. This study consists of a 28 day Screening Period, a 52 week Treatment Period; including a 12 week double blinded (Cohort 1) or open label (Cohort 2) Induction Phase and a 40 week double blinded (responders) or open label (nonresponders) Maintenance Phase; and a 4 week Follow up Period, which will consist of an End of Study (EOS) visit
Patient eligibility will be determined during a 4 week (28 days) Screening Period. Entry criteria will be based on confirmation of active moderate to severe ileal, ileocolic, or colonic CD. Approximately 930 patients will participate in this study (ABX464 Dose A N = 380, ABX464 Dose B N = 380, placebo N = 170).
On Day 0, eligible patients will be randomized into 2 cohorts:
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Cohort 1: Double blinded Induction Phase according to a 1:1:1 ratio into 3 treatment groups as follows:
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ABX464 - Dose A QD: 170 patients
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ABX464 - Dose B QD: 170 patients
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Matching Placebo: 170 patients
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Cohort 2: Open-label Induction Phase according to a 1:1 ratio into 2 treatment groups as follows:
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)
盲法说明
Double-Blind Treatment
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men or women age 18-75 years;
- •Patients must have a documented diagnosis (endoscopic with histology) of CD for ≥ 3 months before screening;
- •Patients must have active moderate to severe ileal, ileocolic, or colonic CD at baseline as defined by 220 ≤ CDAI > 450,
- •Patients must have a SES-CD score > 6 (≥4 if isolated ileal disease) at screening, assessed by ileocolonoscopy and confirmed by a central reading.
- •Patients must be willing and able to undergo endoscopy during screening after all other inclusion criteria have been met and at the end of Week
- •Patients must have had either a documented inadequate response, no response, a loss of response, or an intolerance (defined as the occurrence of at least one Adverse Reaction leading to treatment discontinuation) to either amino-salicylates, immunosuppressant treatment (i.e., azathioprine, 6-mercaptopurine, methotrexate, biologics (i.e. tumor necrosis factor inhibitors, vedolizumab, ustekinumab), and/or corticosteroid treatment.
- •Patients should be able and willing to comply with study visits and procedures as per protocol;
- •Patients should understand, sign and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures being performed;
- •Patients should be affiliated to a social security regimen (for French sites only);
- •Females and males receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for 3 months after end of study or early termination.
排除标准
- •Patients with indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis or clinical/histologic findings suggestive of ulcerative colitis;
- •Patients with colonic dysplasia or neoplasia or adenomatous colonic polyp;
- •Patients with presence of fistulae;
- •Patients with current symptomatic diverticulitis or diverticulosis;
- •Patients with obstructive colonic stricture/stenosis, past medical history of colonic resection, a history of bowel surgery within 6 months before screening, or who are likely to require surgery for CD during the treatment period;
- •Patients with past medical history of clinically significant short bowel syndrome;
- •Patients requiring parenteral nutrition;
- •Patients with past medical history of bowel surgery resulting in an existing or current stoma;
- •Patients with active infections at screening such as infected abdominal abscess, Clostridium difficile (stool antigen and toxin required), cytomegalovirus, tuberculous colitis and recent infectious hospitalization;
- •Acute, chronic or history of clinically relevant pulmonary, cardiovascular, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable central nervous system pathology such as seizure disorder, angina or cardiac arrhythmias, or any other clinically significant medical problems as determined by physical examination and/or laboratory screening tests and/or medical history;
- •Acute, chronic or history of immunodeficiency or autoimmune disease;
- •History of malignancy excluding patients considered cure (5 years disease free survivors);
- •Active malignancy that may require chemotherapy or radiation therapy;
- •Serious illness requiring systemic treatment and/or hospitalization within 3 Weeks prior to baseline;
- •Pregnant or breast-feeding woman;
- •Illicit drug or alcohol abuse or dependence;
- •Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding baseline, whichever is longer;
- •Any condition, which in the opinion of the investigator, could compromise the patient's safety or adherence to the study protocol.
研究组 & 干预措施
ABX464 dose A
Dose A QD
干预措施: ABX464 (Drug)
ABX464 Dose B
Dose B QD
干预措施: ABX464 (Drug)
Placebo
Matching dose
干预措施: Placebo (Drug)
结局指标
主要结局
The co-primary objectives of the study are to determine the efficacy of ABX464 in inducing clinical remission and endoscopic improvement after 12 weeks of study treatment in patients with moderate to severe active CD who have inadequate response, loss of
时间窗: from baseline, at Week 12
Percentage of patients in clinical remission at Week 12, defined as CDAI of ≤ 150
Co-primary objectives of the study are to determine the efficacy of ABX464 in inducing clinical remission and endoscopic improvement after 12 weeks of study treatment in patients with moderate to severe active CD who have inadequate response, loss of
时间窗: from baseline, at Week 12
Percentage of patients with endoscopic improvement at Week 12, defined as a decrease from baseline of ≥ 50% in the global SES-CD (SES CD 50)
次要结局
- To evaluate the effect of ABX464 on C reactive protein (CRP) and fecal calprotectin levels(from baseline, at week 12)
- To evaluate the effect of ABX464 on patients' quality of life(from baseline to week 12)
- To evaluate the effect of ABX464 on micro RNA (miR) 124 expression in whole blood and in tissue(from baseline to week 12)
- To evaluate the effect of ABX464 as measured by endoscopic remission at Week 12(from baseline, at week 12)
- To assess the pharmacokinetics of ABX464 and ABX464-N-Glu(from baseline, at week 12)
- To evaluate the effect of ABX464 as measured by clinical response at Week 12(from baseline, at week 12)
- To evaluate the safety of ABX464(from baseline, at week 12)
- To evaluate the effect of ABX464 as measured by Patient-Reported-Outcome-based remission (PRO) at Week 12(from baseline, at week 12)