A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study in Healthy Participants Followed by a Randomized, Double-Blind, Placebo-Controlled Phase 2 Study in Participants With Moderate-To-Severe Active Ulcerative Colitis.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Xencor, Inc.
- 入组人数
- 270
- 试验地点
- 90
- 主要终点
- Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of XmAb942 in healthy volunteers (Part A)
研究概览
简要总结
The Phase 1 study described herein will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of XmAb942 in healthy volunteers (Parts A and B). Part C of this study will be a Phase 2 study to evaluate XmAb942 in participants with ulcerative colitis (UC).
详细描述
This study consists of 3 parts, as follows:
Part A: Single ascending dose (SAD) in healthy participants, will entail administration of XmAb942 or matching placebo at 3 different dose levels of XmAb942.
Part B: Multiple ascending dosing for up to 3 doses, will entail administration of XmAb942 or matching placebo at 2 different dose levels of XmAb942.
Part C: Participants with moderately to severely active UC to receive 3 different dose levels of XmAb942 or placebo during a 12-week induction period and single dose level of XmAb942 during a 40-week maintenance period, followed by a 24 week follow-up period.
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
- Double (Participant, Investigator)
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
- 是
入选标准
- •Parts A and B
- •Age 18-55
- •Must be in good health with no significant medical history
- •Clinical laboratory values within normal range
- •BMI 18-35 (inclusive)
- •Contraceptive use by men or women consistent with local regulations
- •Able and willing to provide written informed consent
- •Age 18-75
- •Must be in good health with no significant medical history
- •UC diagnosis ≥ 3 months prior to screening
- •Diagnosis of moderately to severely active UC as defined by a (MMS) ≥ 5, with a MES ≥ 2 and RBS ≥ 1
- •Evidence of UC extending ≥ 15 cm from the anal verge, as determined by screening colonoscopy
- •Must have inadequate response to, loss of response to, or intolerance to at least 1 of the conventional or advanced therapies of UC
- •Able and willing to provide written informed consent
排除标准
- •Parts A and B
- •Any physical or psychological condition that prohibits study completion
- •History of suicidal behavior or suicidal ideation
- •Heavy use of nicotine containing products
- •HIV, hepatitis B and hepatitis C positive
- •Cardiac arrhythmia, or clinically significant abnormal ECG
- •Active use of prescription medications within 14 days of Day -1
- •Active use of over-the-counter, or herbal medication within 7 days of Screening
- •Other investigational products within 30 days
- •Blood or plasma donation within 60 days
- •Pregnant or breastfeeding
- •Any physical or psychological condition that prohibits study participation
- •Diagnosis of Crohn disease, indeterminate colitis, indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, and diverticular disease associated with colitis.
- •Positive screen for Clostridium difficile (C. Difficile) toxins
- •HIV, hepatitis B and hepatitis C positive
- •Cardiac arrhythmia, or clinically significant abnormal ECG
- •Pregnant or breastfeeding
- •Other protocol defined inclusion/exclusion criteria apply.
研究组 & 干预措施
Part A: Placebo
Placebo Comparator to be administered to healthy volunteers. Single administration of 3 ascending dose (SAD) levels will be randomized in a 3:1 ratio to active or placebo.
干预措施: Placebo (Drug)
Part B: Placebo
Placebo Comparator to be administered to healthy volunteers. Multiple administrations of 2 ascending dose (MAD) levels will be randomized in a 3:1 ratio to active or placebo.
干预措施: Placebo (Drug)
Part C: placebo
Placebo comparator to be administered to participants with moderately to severely active Ulcerative Colitis
干预措施: Placebo (Drug)
Part A: Active drug
Active XmAb942 to be administered to healthy volunteers. Single administration of 3 ascending dose (SAD) levels of XmAb942 via SC (3 cohorts) or IV (3 cohorts) administration in 8 participants per cohort, randomized in a 3:1 ratio to active or placebo.
干预措施: XmAb942 (Biological)
Part B: Active
Active XmAb942 to be administered to healthy volunteers. Multiple administrations of 2 ascending dose (MAD) levels of XmAb942 via IV administration in 8 participants per cohort, randomized in a 3:1 ratio to active or placebo.
干预措施: XmAb942 (Biological)
Part C: Active
Active XmAb942 to be administered to participants with moderately to severely active Ulcerative Colitis
干预措施: XmAb942 (Biological)
结局指标
主要结局
Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of XmAb942 in healthy volunteers (Part A)
时间窗: 20 weeks
Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of XmAb942 in healthy volunteers (Part B)
时间窗: 28 weeks
Clinical remission based on modified mayo score (MMS), defined as MMS ≤ 2 with Mayo endoscopic score (MES) of 1, rectal bleeding subscore (RBS) of 0, and stool frequency subscore (SFS) of 0-1.
时间窗: 12 weeks
A composite score of ulcerative colitis (UC) disease activity on a scale of increasing severity from 0-9. It is calculated by adding the results from Mayo endoscopic subscore (MES) which measures GI bleeding, stool frequency subscore (SFS) which measures stool frequency per day, and rectal bleeding subscore (RBS), which measures presence of blood during stool passing. Each subscore is a scale of increasing severity from 0 to 3.
次要结局
- Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) (Part C)(72 weeks)
- Discontinuations due to TEAEs (Part C)(72 weeks)
- Serum PK parameters of XmAb942 in Healthy Volunteers (Part A)(up to 20 weeks)
- Serum PK parameters of XmAb942 in Healthy Volunteers (Part B)(up to 28 weeks)
- Endoscopic improvement defined as (MES) of 0 or 1 (Part C).(12 weeks)
- Change from baseline in MS (Part C).(12 weeks)
- Clinical response based on MMS score (Part C) defined as decrease from baseline in the MMS of ≥ 2 points and at least a 30% reduction from baseline, and decrease of ≥ 1 point in RBS from baseline or absolute RBS ≤ 1(12 weeks)
- Histological improvement as determined by change in Robarts Histopathology Index (RHI) scores, ranging from 0 (no disease activity) to 33 (severe disease activity).(12 weeks)