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.
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Ulcerative Colitis (UC)
- Sponsor
- Xencor, Inc.
- Enrollment
- 270
- Locations
- 53
- Primary Endpoint
- Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of XmAb942 in healthy volunteers (Part A)
- Status
- Recruiting
- Last Updated
- 19 days ago
Overview
Brief Summary
Brief summary 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).
Detailed Description
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: Repeat 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: Placebo
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.
Intervention: Placebo
Part C: placebo
Placebo comparator to be administered to participants with moderately to severely active Ulcerative Colitis
Intervention: Placebo
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.
Intervention: XmAb942
Part C: Active
Active XmAb942 to be administered to participants with moderately to severely active Ulcerative Colitis
Intervention: XmAb942
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.
Intervention: XmAb942
Outcomes
Primary Outcomes
Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of XmAb942 in healthy volunteers (Part A)
Time Frame: 20 weeks
Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of XmAb942 in healthy volunteers (Part B)
Time Frame: 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.
Time Frame: 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.
Secondary Outcomes
- 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)