Study of XmAb942 in Healthy Participants and Participants With Ulcerative Colitis

Xencor

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Ulcerative Colitis (UC)

Treatments

Drug: Placebo

Biological: XmAb942

Study type

Interventional

Funder types

Industry

Identifiers

NCT06619990

XmAb942-01 (G942-101)

Details and patient eligibility

About

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).

Full 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.

Enrollment

270 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

Accepts Healthy Volunteers

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/exclusion criteria apply.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

270 participants in 6 patient groups, including a placebo group

Part A: Active drug

Active Comparator group

Description:

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.

Treatment:

Biological: XmAb942

Part A: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Part B: Active

Active Comparator group

Description:

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.

Treatment:

Biological: XmAb942

Part B: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Part C: Active

Active Comparator group

Description:

Active XmAb942 to be administered to participants with moderately to severely active Ulcerative Colitis

Treatment:

Biological: XmAb942

Part C: placebo

Placebo Comparator group

Description:

Placebo comparator to be administered to participants with moderately to severely active Ulcerative Colitis