Study of XmAb942 in Healthy Participants and Participants With Ulcerative Colitis
- Registration Number
- NCT06619990
- Lead Sponsor
- GALE Therapeutics Inc.
- 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.
- Detailed Description
This study is a Phase 1 randomized, double-blind, placebo-controlled, single ascending dose (SAD) study in healthy volunteers, followed by a cohort of three repeating doses in healthy volunteers. The third part of this study will be a Phase 2, randomized, placebo controlled, double blind evaluation of participants with Ulcerative Colitis with a dose determined from Parts A and B.
This study consists of 3 parts, as follows:
Part A: SAD in healthy participants, will entail administration of XmAb942 or matching placebo.
Part B: Repeat Dosing for up to 3 doses, will entail administration of XmAb942 or matching placebo.
Part C: Participants with UC to receive XmAb942 or placebo with dose determined from Part A and Part B.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
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 18-55
- Must be in good health with no significant medical history
- UC diagnosis
- 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
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 completion
- Diagnosis of Crohn disease, pouchitis, or indeterminate colitis
- Positive screen for Clostridium difficile (C. Difficile)
- 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
- Other investigational products within 30 days
- Blood or plasma donation within 60 days
- Pregnant or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part C: Active XmAb942 Active XmAb942 to be administered to participants with Ulcerative Colitis. The SRC will provide recommendations on the doses in Part C based on emerging Part A and/or Part B data. Part C: placebo Placebo Placebo Comparator to be administered to participants with Ulcerative Colitis. The SRC will provide recommendations on the doses, frequency and route of administration to be assessed in Part C based on emerging Part A and/or Part B data Part A: Active drug XmAb942 Active XmAb942 to be administered to healthy volunteers (SAD). Participants will be randomized in a 3:1 ratio to active or placebo. Study intervention will be administered once via either subcutaneous injection or intravenous infusion. Each dose cohort will have 8 participants receiving the dose as a subcutaneous injection, and 8 participants receiving the dose as an IV infusion. Randomization to each SAD cohort will be done in a staggered manner; initially 2 sentinel participants (1 active and 1 placebo) will be randomized and dosed. After a safety evaluation period of the dose without clinically significant adverse events (AEs) then 6 additional participants will be randomized and dosed (5 active and 1 placebo) at the discretion of the Investigator according to the randomization schedule. A Safety Review Committee (SRC) will review data prior to escalation to the next dose level. Part A: Placebo Placebo Placebo Comparator to be administered to healthy volunteers (SAD). Participants will be randomized in a 3:1 ratio to active or placebo. Study intervention will be administered once via either subcutaneous injection or intravenous infusion. Each dose cohort will have 8 participants receiving the dose as a subcutaneous injection, and 8 participants receiving the dose as an IV infusion. Randomization to each SAD cohort will be done in a staggered manner; initially 2 sentinel participants (1 active and 1 placebo) will be randomized and dosed. After a safety evaluation period of the dose without clinically significant adverse events (AEs) then 6 additional participants will be randomized and dosed (5 active and 1 placebo) at the discretion of the Investigator according to the randomization schedule. A Safety Review Committee (SRC) will review data prior to escalation to the next dose level. Part B: Active XmAb942 Active XmAb942 to be administered to healthy volunteers. Participants will be randomized in a 3:1 ratio to active or placebo. Determination of route of administration will be performed by SRC prior to initiation of Part B. Each dose cohort will have 8 participants receiving the dose as a subcutaneous infusion, and 8 participants receiving the dose as an IV infusion. The SRC may review data for determination of the next dose cohort. Part B: Placebo Placebo Placebo Comparator to be administered to healthy volunteers. Participants will be randomized in a 3:1 ratio to active or placebo. Determination of route of administration will be performed by SRC prior to initiation of Part B. Each dose cohort will have 8 participants receiving the dose as a subcutaneous infusion, and 8 participants receiving the dose as an IV infusion. The SRC may review data for determination of the next dose cohort.
- Primary Outcome Measures
Name Time Method Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of XmAb942 in healthy volunteers (Part A cohort) 20 weeks Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) with repeated doses of XmAb942 in healthy volunteers (Part B cohort) 28 weeks Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) with repeated doses of XmAb942 in participants with UC (Part C) 12 weeks Clinical outcomes of multiple doses of XmAb942 in participants with UC, as determined by the Modified Mayo Score, Rectal Bleeding score, Stool Frequency Score, and Endoscopic subscore (Part C) 12 weeks The Modified Mayo Score (MMS) is a composite score of ulcerative colitis (UC) disease activity on a scale of increasing severity from 0-9. This is calculated by adding the results from Endoscopic Subscore (ES) which measures GI bleeding, Stool Frequency Subscore (SFS) which measures stool frequency per day, and Rectal Bleeding Score (RBS), which measures presence of blood during stool passing. Each subscore is a scale of increasing severity from 0 to 3.
- Secondary Outcome Measures
Name Time Method Proportion of participants with histologic-endoscopic remission (Part C). 12 weeks Histologic-endoscopic remission (HER) is defined as a Geboes score of less than 2 and ES of 0 or 1. The Geboes score is a histologic grading system for inflammation in UC with scores ranging from 0 to 5.4, with higher scores indicating more severe inflammation. ES measures UC severity based on endoscopy, scored from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration).
Proportion of participants with endoscopic remission (Part C). 12 weeks Endoscopic improvement is defined as Mayo endoscopic subscore (ES) of 0 or 1. The ES measures UC severity based on endoscopy on a 0-3 scale of increasing severity.
Proportion of participants with endoscopic improvement (Part C) 12 weeks Endoscopic improvement is defined as Mayo endoscopic subscore (ES) of 0 or 1. The ES measures UC severity based on endoscopy on a 0-3 scale of increasing severity.
Proportion of participants with histologic-endoscopic improvement (Part C). 12 weeks Histologic-endoscopic improvement is defined as a Geboes score ≤3.1, together with a Mayo Score for ES of 0 or 1. The Geboes score is a histologic grading system for inflammation in UC with scores ranging from 0 to 5.4, with higher scores indicating more severe inflammation. The ES measures UC severity based on endoscopy on a 0-3 scale of increasing severity.
Change from baseline in partial Modified Mayo score (Part C). 12 weeks The partial Modified Mayo Score (pMMS) is a composite score of UC disease activity on a scale of increasing severity from 0-6, calculated by summing two subscores: SFS, scored from 0 (typical number of stools per day for the participant) to 3 (≥5 stools more than normal per day for the participant); RBS, scored from 0 (no blood seen) to 3 (only passing blood). Clinical response is defined as pMMS reduction of 1 or more points and 30% or more, plus a reduction of 1 or more points in RBS or an absolute RBS of 0 or 1.
Proportion of participants with clinical response per Modified Mayo Score (MMS) (Part C). 12 weeks The Modified Mayo Score (MMS) is a composite score of ulcerative colitis (UC) disease activity on a scale of increasing severity from 0-9. This is calculated by adding the results from Endoscopic Subscore (ES) which measures bleeding GI bleeding, Stool Frequency Subscore (SFS) which measures stool frequency per day, and Rectal Bleeding Score, which measures presence of blood during stool passing. Each subscore is a scale of increasing severity from 0 to 3.
Plasma pharmacokinetics of XmAb942 in healthy volunteers (subcutaneous cohort) up to 28 weeks AUC0-tau AUC within a dosing interval, calculated using the linear trapezoidal rule
Plasma pharmacokinetics of XmAb942 in healthy volunteers (IV cohort) up to 28 weeks AUC0-tau AUC within a dosing interval, calculated using the linear trapezoidal rule
Plasma pharmacokinetics of XmAb942 in participants with Ulcerative Colitis (Part C) up to 12 weeks CL/F (Apparent) total body clearance, calculated as: Dose / AUCinf or Dose / AUCtau (steady state)
Trial Locations
- Locations (1)
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia