Phase 2 Platform Trial to Assess the Efficacy and Safety of Long-acting Antibodies as Single Agents and in Combinations for Moderately to Severely Active Ulcerative Colitis
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 645
- 试验地点
- 10
- 主要终点
- PART A: To assess the effects of intervention on
研究概览
简要总结
This is a Phase 2 multi-center, double-blind, randomized, open-label (Part A) and placebo-controlled (Part B) proof-of-concept platform study in participants with moderately to severely active UC.
In Part A of the study, which is open-label, 3 interventions are currently planned to be evaluated as monotherapies. The purpose of Part A is to generate preliminary proof-of-concept safety and efficacy data in initial cohorts of participants with UC for each monotherapy intervention, to enable modifications as needed in Part B (eg, sample size), confirm intervention specific treatment features, and further inform subsequent Part B cohorts.
In Part B of the study, which is placebo-controlled, the treatment arms will consist of monoclonal -controlled proof-of-concept efficacy and safety data to inform further development of each intervention.
The duration of individual participation will be up to approximately 97 weeks, and treatment duration will be up to approximately 48 weeks
The main objectives of the study is to assess the effects of intervention on histologic disease activity, clinical remission, endoscopic improvement, clinical disease activity, pharmacokinetics, anti-drug antibodies at week 12 for both part A and B.
The total sample size for PART A and Part B combined is approximately 645 globally and 35 patients from India.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 64.00 Year(s)（—）
- 性别
- All
入选标准
- •Adult participants must have had a diagnosis of UC for greater than or equal to 3 months before Day 1 confirmed by endoscopy and histology either previously or during Screening.
- •If documentation of confirmatory endoscopy or histology is not available for review, additional biopsies during screening endoscopy may be performed and sent to a local histology laboratory for histologic assessment documenting findings consistent with UC.
- •On histology, any mention of UC, chronic inflammation, or equivalent is considered adequate.
- •Active UC with disease extent of greater than or equal to 15 cm from the anal verge, as confirmed by Screening endoscopy, with the exception of up to approximately 15 percentage of the total population permitted to have only proctitis (less than15 cm from the anal verge).
- •Moderately to severely active disease as defined by a modified Mayo score of 5 to 9, rectal bleeding subscore of greater than or equal to 1, and Mayo endoscopic subscore greater than or equal to
- •History of corticosteroid dependence, OR inadequate response,1 OR loss of response, 2 OR intolerance to 1 of the following: a.
- •conventional therapy only (oral locally acting or systemic corticosteroids, or immunosuppressants) (target of approximately 40 percentage – 60 percentage of the planned sample size) OR b.
- •approved advanced therapies, ie anti-TNF, anti-alpha4beta7, anti-IL-12 or IL-23, anti-IL-23, JAK inhibitors, or S1P receptor antagonists), as defined in the full protocol (target of approximately 40 percentage to 60 percentage of the planned sample size).
- •Participants taking oral corticosteroids (up to 20 mg per day prednisone or equivalent, 9 mg per day budesonide, or 5 mg per day beclomethasone) must be on a stable dose for greater than or equal to 2 weeks prior to Day 1 and be willing to stay on the same dose during the ITP (for Part A participants), or through Week 6 and initiate taper at Week 6 (for Part B participants).
排除标准
- •Failed (inadequate, lack, or loss of response or intolerance to) 4 or more approved or investigational advanced therapy classes (anti-TNF, anti-alpha4beta7, anti-IL-12 or IL-23, anti-IL-23, JAK inhibitors, and S1P receptor antagonists) at the approved labeled dose or higher, if applicable.
- •Failed (inadequate response, loss of response, or intolerance to) 2 or more of the following classes (whether drug is approved or investigational) at an approved labeled dose or higher, if applicable: – anti-alpha4beta7 (eg, vedolizumab), – anti-TL1A, or – anti-IL-23 (eg, mirikizumab, guselkumab, risankizumab).
结局指标
主要结局
PART A: To assess the effects of intervention on
时间窗: PART A: Change in RHI from baseline at Week 12 | PART B: Clinical remission at Week 12
histologic disease activity following 12 weeks of treatment
时间窗: PART A: Change in RHI from baseline at Week 12 | PART B: Clinical remission at Week 12
PART B: To assess the efficacy of intervention in inducing
时间窗: PART A: Change in RHI from baseline at Week 12 | PART B: Clinical remission at Week 12
clinical remission following 12 weeks of treatment
时间窗: PART A: Change in RHI from baseline at Week 12 | PART B: Clinical remission at Week 12
次要结局
- PART A: To assess the efficacy of intervention in inducing clinical remission following 12 weeks of treatment(Clinical remission at Week 12)
- PART A: To assess the efficacy of intervention in inducing(endoscopic improvement following 12 weeks of)
- PART B: To assess the efficacy of intervention in inducing endoscopic improvement following 12 weeks of treatment(Endoscopic improvement at Week 12)
- PART B: To assess the efficacy of intervention in inducing(clinical response following 12 weeks of treatment)
- PART B: To assess the efficacy of intervention in inducing(histologic improvement following 12 weeks of)
- PART B: To assess the efficacy of intervention in inducing(HEMI following 12 weeks of treatment)
- PART B: To assess the efficacy of(intervention in achieving)
研究者
Dr Radhika Bobba
PSI CRO PHARMA India Private Limited