An Early-Stage Study in Multiple Clinics of How Afimkibart May Affect the Body's Processing of Medicines That Rely on Cytochrome P450 Enzymes in Participants With Ulcerative Colitis

Официальное название

A Phase I, Multicenter, Open-Label, Single-Agent Study to Assess the Pharmacokinetics of Cytochrome P450 Substrates After Treatment With Afimkibart in Participants With Moderately to Severely Active Ulcerative Colitis

Обзор

The purpose of this study is to evaluate the disease-drug-drug interaction (DDDI) potential of afimkibart (also known as RO7790121). This will be assessed by the characterization of the pharmacokinetics (PK) of cytochrome P450 (CYP) enzyme substrates alone and after administration of afimkibart in participants with moderately to severely active ulcerative colitis (UC).

Вмешательства

• Препарат Afimkibart
  Afimkibart will be administered as per the schedule defined in the protocol.
• Препарат Caffeine
  Caffeine will be administered orally as part of a CYP cocktail per the schedule defined in the protocol.
• Препарат Warfarin
  Warfarin will be administered orally as part of a CYP cocktail per the schedule defined in the protocol.
• Препарат Omeprazole
  Omeprazole will be administered orally as part of a CYP cocktail per the schedule defined in the protocol.
• Препарат Dextromethorphan
  Dextromethorphan will be administered orally as part of a CYP cocktail per the schedule defined in the protocol.
• Препарат Midazolam
  Midazolam will be administered orally as part of a CYP cocktail per the schedule defined in the protocol.
• Другое Vitamin K
  Vitamin K will be administered orally as a rescue medication following warfarin administration per the schedule outlined in the protocol.

Первичные конечные точки

• Area Under the Plasma Concentration-time Curve Up to Time t (AUC0-t [AUC last]) of CYP Probe Substrates (Midazolam, 1-OH-Midazolam, Omeprazole, 5-OH-Omeprazole, Dextromethorphan, Dextrorphan, R-Warfarin, S-Warfarin, Caffeine, and Paraxanthine) [Срок оценки: Up to approximately 13 weeks]
• Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (AUCinf) of CYP Probe Substrates (Midazolam, 1-OH-Midazolam, Omeprazole, 5-OH-Omeprazole, Dextromethorphan, Dextrorphan, R-Warfarin, S-Warfarin, Caffeine, and Paraxanthine) [Срок оценки: Up to approximately 13 weeks]
• Maximum Plasma Concentration (Cmax) of CYP Probe Substrates (Midazolam, 1-OH-Midazolam, Omeprazole, 5-OH-Omeprazole, Dextromethorphan, Dextrorphan, R-Warfarin, S-Warfarin, Caffeine, and Paraxanthine) [Срок оценки: Up to approximately 13 weeks]
• Time to Maximum Concentration (Tmax) of CYP Probe Substrates (Midazolam, 1-OH-Midazolam, Omeprazole, 5-OH-Omeprazole, Dextromethorphan, Dextrorphan, R-Warfarin, S-Warfarin, Caffeine, and Paraxanthine) [Срок оценки: Up to approximately 13 weeks]
• Elimination Half-life (T1/2) of CYP Probe Substrates (Midazolam, 1-OH-Midazolam, Omeprazole, 5-OH-Omeprazole, Dextromethorphan, Dextrorphan, R-Warfarin, S-Warfarin, Caffeine, and Paraxanthine) [Срок оценки: Up to approximately 13 weeks]
• Metabolite-to-parent Area Under the Curve From Time 0 (AUC0-t) Ratio for CYP Probe Substrates (Midazolam and 1-OH-Midazolam, Omeprazole and 5-OH-Omeprazole, Dextromethorphan and Dextrorphan, and Caffeine and Paraxanthine) [Срок оценки: Up to approximately 13 weeks]
• Metabolite-to-parent Area Under the Concentration-time Curve from Time 0 to Infinity (AUC0-inf) Ratio for CYP Probe Substrates (Midazolam and 1-OH-Midazolam, Omeprazole and 5-OH-Omeprazole, Dextromethorphan and Dextrorphan, and Caffeine and Paraxanthine) [Срок оценки: Up to approximately 13 weeks]
• Metabolite-to-parent Concentration of CYP Probe Substrates (Midazolam and 1-OH-Midazolam, Omeprazole and 5-OH-Omeprazole, Dextromethorphan and Dextrorphan, and Caffeine and Paraxanthine) [Срок оценки: Up to approximately 13 weeks]

Вторичные конечные точки (2)

• Percentage of Participants with Adverse Events (AEs) [Срок оценки: Up to approximately 5 years]
• Predose and Peak Serum Concentration of Afimkibart [Срок оценки: Up to approximately 5 years]

Критерии участия

Критерии включения

• Body weight >= 40kg
• Agreement to adhere to the contraceptive requirements

UC Specific Inclusion Criteria:

• Confirmed diagnosis of UC with supportive clinical, endoscopic, and histopathological evidence
• Active UC confirmed by endoscopy (flexible sigmoidoscopy or colonoscopy) extending >=15 cm from the anal verge
• Moderately to severely active UC, defined as an modified Mayo score of 5 to 9 points, including a Mayo endoscopic subscore of 2 or 3, confirmed through centrally read endoscopy

Критерии исключения

Inflammatory Bowel Disease (IBD) Exclusion Criteria:

• Current diagnosis of Crohn's disease (CD),abdominal/intrabdominal/perianal fistula and/or abscess, indeterminant colitis, IBD-unclassified, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, or active diverticular disease
• Presence of an ostomy or ileoanal pouch
• Current diagnosis or suspicion of primary sclerosing cholangitis

Medical History Exclusion Criteria:

• Lack of peripheral venous access
• Any major surgery within 6 weeks prior to screening or a major surgery planned during the study
• History of alcohol, drug, or chemical abuse < 1 year prior to screening

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• Erick H. Alayo Medical Corporation - Gastro SB Clinic — Chula Vista
• Allied Biomedical Research Institute, Inc — Miami
• Gastro Health Research — Miami

Великобритания · 3 центра

• Royal Liverpool University Hospital — Liverpool
• University College London Hospitals — London
• Royal Victoria Infirmary — Newcastle upon Tyne

Германия · 1 центр

• Charite Research Organisation GmbH — Berlin

Идентификаторы

NCT: NCT07665723 · GA46438 · 2025-524060-38-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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