Ulcerative Colitis (UC)
Conditions
Keywords
Ulcerative Colitis, Inflammatory Bowel Disease, Healthy Volunteers
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 volunteer 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 36 follow-up period.
Interventions
BIOLOGICALXmAb942
Antibody
DRUGPlacebo
Placebo
Sponsors
Xencor, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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 Part C * 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
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 * Pregnant or breastfeeding Part C * 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of XmAb942 in healthy volunteers (Part A) | 20 weeks | — |
| Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of XmAb942 in healthy volunteers (Part B) | 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. | 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
| Measure | Time frame | Description |
|---|---|---|
| Serum PK parameters of XmAb942 in Healthy Volunteers (Part A) | up to 20 weeks | • Cmax (Maximum concentration of drug) |
| Serum PK parameters of XmAb942 in Healthy Volunteers (Part B) | up to 28 weeks | • Cmax (Maximum concentration of drug) |
| 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 | — |
| 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 | — |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Croatia, Georgia, Greece, Hungary, Moldova, Poland, Portugal, Romania, Ukraine, United States
Contacts
CONTACT942 Study Information
STUDY_DIRECTOR942 Study Information
Xencor, Inc.
Outcome results
None listed