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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
270
Xencor Investigative Site
Scottsdale, Arizona, United States
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.
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.
Time frame: 12 weeks
Serum PK parameters of XmAb942 in Healthy Volunteers (Part A)
• Cmax (Maximum concentration of drug)
Time frame: up to 20 weeks
Serum PK parameters of XmAb942 in Healthy Volunteers (Part A)
• AUC0-last (Area under the curve drug concentration-time curve to last concentration)
Time frame: up to 20 weeks
Serum PK parameters of XmAb942 in Healthy Volunteers (Part B)
• Cmax (Maximum concentration of drug)
Time frame: up to 28 weeks
Serum PK parameters of XmAb942 in Healthy Volunteers (Part B)
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Xencpr Investigative Site
Jacksonville, Florida, United States
RECRUITINGXencor Investigative Site
Kissimmee, Florida, United States
RECRUITINGXencor Investigative Site
Tampa, Florida, United States
RECRUITINGXencor Investigative Site
Raleigh, North Carolina, United States
RECRUITINGXencor Investigative Site
Kingwood, Texas, United States
RECRUITINGXencor Investigative Site
San Antonio, Texas, United States
RECRUITINGXencor Investigative Site
Wollongong, New South Wales, Australia
RECRUITINGXencor Investigative Site
South Brisbane, Queensland, Australia
RECRUITINGXencor Investigative Site
Joondalup, Western Australia, Australia
COMPLETED...and 11 more locations
• AUC0-tau AUC within a dosing interval, calculated using the linear trapezoidal rule
Time frame: up to 28 weeks
Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) (Part C)
Time frame: 72 weeks
Discontinuations due to TEAEs (Part C)
Time frame: 72 weeks
Endoscopic improvement defined as (MES) of 0 or 1 (Part C).
Time frame: 12 weeks
Change from baseline in MS (Part C).
Time frame: 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
Time frame: 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).
Time frame: 12 weeks