Study of XmAb942 in Healthy Participants and Participants With Ulcerative Colitis

Официальное название

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.

Обзор

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).

Подробное описание

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: 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 24 week follow-up period.

Вмешательства

• Биопрепарат XmAb942
  Antibody
• Препарат Placebo
  Placebo

Первичные конечные точки

• Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of XmAb942 in healthy volunteers (Part A) [Срок оценки: 20 weeks]
• Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of XmAb942 in healthy volunteers (Part B) [Срок оценки: 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. [Срок оценки: 12 weeks]

Вторичные конечные точки (10)

• Serum PK parameters of XmAb942 in Healthy Volunteers (Part A) [Срок оценки: up to 20 weeks]
• Serum PK parameters of XmAb942 in Healthy Volunteers (Part A) [Срок оценки: up to 20 weeks]
• Serum PK parameters of XmAb942 in Healthy Volunteers (Part B) [Срок оценки: up to 28 weeks]
• Serum PK parameters of XmAb942 in Healthy Volunteers (Part B) [Срок оценки: up to 28 weeks]
• Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) (Part C) [Срок оценки: 72 weeks]
• Discontinuations due to TEAEs (Part C) [Срок оценки: 72 weeks]
• Endoscopic improvement defined as (MES) of 0 or 1 (Part C). [Срок оценки: 12 weeks]
• Change from baseline in MS (Part C). [Срок оценки: 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 [Срок оценки: 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). [Срок оценки: 12 weeks]

Критерии участия

Критерии включения

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

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 29 центров

• Xencor Investigative Site — Scottsdale
• Xencor Investigative Site — Bradenton
• Xencor Investigative Site — Brandon
• Xencor Investigative Site — Jacksonville
• Xencor Investigative Site — Kissimmee
• Xencor Investigative Site — Margate
• Xencor Investigative Site — Palmetto Bay
• Xencor Investigative Site — Tampa
• … и ещё 21 центр

Польша · 12 центров

• Xencor Investigative Site — Bydgoszcz
• Xencor Investigative Site — Katowice
• Xencor Investigative Site — Krakow
• Xencor Investigative Site — Nowy Targ
• Xencor Investigative Site — Sopot
• Xencor Investigative Site — Staszów
• Xencor Investigative Site — Szczecin
• Xencor Investigative Site — Warsaw
• … и ещё 4 центра

Украина · 11 центров

• Xencor Investigative Site — Ivano-Frankivsk
• … и ещё 10 центров

Австралия · 7 центров

• Xencor Investigative Site — Adelaide
• Xencor Investigative Site — Joondalup
• Xencor Investigative Site — Melbourne
• Xencor Investigative Site — Nedlands
• Xencor Investigative Site — South Brisbane
• Xencor Investigative Site — Southport
• Xencor Investigative Site — Wollongong

Бразилия · 5 центров

• Xencor Investigative Site — Campinas
• Xencor Investigative Site — Porto Alegre
• Xencor Investigative Site — Santo André
• Xencor Investigative Site — São Paulo
• Xencor Investigative Site — Votuporanga

Венгрия · 5 центров

• Xencor Investigative Site — Budapest
• Xencor Investigative Site — Budapest
• Xencor Investigative Site — Budapest
• Xencor Investigative Site — Nyíregyháza
• Xencor Investigative Site — Vác

Канада · 4 центра

• Xencor Investigative Site — London
• Xencor Investigative Site — Montreal
• Xencor Investigative Site — Scarborough
• Xencor Investigative Site — Vancouver

Румыния · 4 центра

• Xencor Investigative Site — Bucharest
• Xencor Investigative Site — Cluj-Napoca
• Xencor Investigative Site — Ploieşti
• Xencor Investigative Site — Timișoara

Аргентина · 3 центра

• Xencor Investigative Site — Buenos Aires
• Xencor Investigative Site — Rosario
• Xencor Investigative Site — San Miguel de Tucumán

Хорватия · 3 центра

• Xencor Investigative Site — Osijek
• Xencor Investigative Site — Rijeka
• Xencor Investigative Site — Zagreb

Греция · 3 центра

• Xencor Investigative Site — Athens
• Xencor Investigative Site — Heraklion
• Xencor Investigative Site — Thessaloniki

Болгария · 1 центр

• Xencor Investigative Site — Sofia

Грузия · 1 центр

• Xencor Investigative Site — Tbilisi

Moldova · 1 центр

• Xencor Investigative Site — Chisinau

Португалия · 1 центр

• Xencor Investigative Site — Loures

Идентификаторы

NCT: NCT06619990 · XmAb942-01 (G942-101)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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