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

Official title

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

Overview

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).

Interventions

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

Primary outcome measures

• 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: Up to approximately 13 weeks]

Secondary outcome measures (2)

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

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

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

United Kingdom · 3 centers

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

Germany · 1 center

• Charite Research Organisation GmbH — Berlin

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗