An Open-label, DDI Study to Investigate the Effects of Duvakitug on the PK of Selected Cytochrome P450 Substrates

An Open-label, Single-sequence Drug-drug Interaction Study to Investigate the Effects of Duvakitug on the Pharmacokinetics of Selected Cytochrome P450 Substrates in Adult Participants With Moderately to Severely Active Ulcerative Colitis or Crohn's Disease

This is an open-label, single group, 2-period, Phase 1, single-arm study. The primary purpose of this study is to investigate the effects of duvakitug on the pharmacokinetics of selected cytochrome P450 substrates in adult participants with moderately to severely active ulcerative colitis or Crohn's disease. Approximately 25 participants will be enrolled. The total study duration per participant will be approximately 166 days.

Study Overview

• Status: Not yet recruiting
• Conditions: Crohn's Disease; Ulcerative Colitis
• Intervention / Treatment: Drug: Duvakitug

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants aged ≥18 and ≤65 years (both inclusive) of age at Screening.

• Ulcerative colitis (UC) participants only:

  • Confirmed diagnosis of UC for at least 3 months prior to Screening.
  • Active UC with a modified Mayo Score of 5 to 9 points and Mayo Endoscopic Subscore of 2 to 3 at Screening (historical endoscopy within 3 months of screening). If no data are available or if available historical endoscopy data are deemed insufficient to determine clinical status, an endoscopy will be performed at Screening.

• Crohn's Disease (CD) participants only:

  • Confirmed diagnosis of CD for at least 3 months prior to Screening.

  • Participants with moderately to severely active CD, defined as:

    1. Persistently active disease with a Crohn's Disease Activity Index score of 220 to 450, with endoscopic Simple Endoscopic Score for Crohn's Disease score (excluding the presence of narrowing component) ≥6 (or ≥4 for participants with isolated ileal disease), (historical endoscopy within 3 months of Screening). If no data are available, an endoscopy will be performed at Screening.
    2. Average daily very soft or liquid stool frequency ≥4.0 and/or average daily abdominal pain score ≥2.0 at Screening.

• Demonstrated inadequate response, loss of response or intolerance to conventional therapies or advanced therapies, in the opinion of the Investigator to at least 1 of following approved treatments:

Conventional therapies

• Immunomodulators (eg, AZA, 6-MP, MTX, tacrolimus, thioguanine).

• IV or oral corticosteroids. Advanced therapies

• Biologics (eg, infliximab, golimumab, adalimumab, certolizumab pegol, natalizumab, vedolizumab, risankizumab, guselkumab, mirikizumab, ustekinumab)

• JAKi (eg, upadacitinib).

• S1PRm (eg, ozanimod, etrasimod).

  • Participant must weigh >40 kg.

Exclusion Criteria:

• For ulcerative colitis (UC) participants only:

  • Participant with a current diagnosis of CD or indeterminate colitis.
  • Participant with a current diagnosis of ulcerative proctitis (disease limited to the rectum) during the screening endoscopy and in the available endoscopic report.
  • Participant with surgical bowel resection within the past 3 months prior to Screening, or a history of >3 bowel resections.

• Crohn's Disease (CD) participants only:

  --Participant with a current diagnosis of UC or indeterminate colitis.

• Participant with the following current complications of UC or CD:

  • Abscess (abdominal or peri-anal),
  • Impassable or symptomatic bowel strictures,
  • Fulminant colitis, or toxic megacolon, or
  • Any other manifestation that might require surgery while enrolled in the study.

• Participant with ostomy or ileoanal pouch.

• Participant diagnosed with short bowel syndrome.

• Poor metabolizers for cytochrome P450 (CYP) 2C9, CYP2C19, or CYP2D6 based on genotyping. Participants who do not consent to this required CYP genotype testing will be excluded from the study.

• Any contraindication to one or more of the following CYP cocktail study interventions, according to the applicable labeling:

  • Caffeine.
  • Metoprolol.
  • Midazolam.
  • Omeprazole.
  • Warfarin.
  • Vitamin K.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Duvakitug; Subcutaneous injection of duvakitug as per protocol and oral administration of caffeine, metoprolol, midazolam, omeprazole, warfarin and vitamin K as per protocol	Drug: Duvakitug; Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection; Other Names: SAR447189

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC for CYP isoform specific substrates midazolam, omeprazole, warfarin, caffeine, and metoprolol	AUC: Area under the plasma concentration versus time curve extrapolated to infinity	At Treatment Period 1 (CYP substrates alone, Day 1) and after 12 weeks of duvakitug (Treatment Period 2, Day 85)
AUClast for CYP isoform specific substrates midazolam, omeprazole, warfarin, caffeine, and metoprolol	AUClast: Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast	At Treatment Period 1 (CYP substrates alone, Day 1) and after 12 weeks of duvakitug (Treatment Period 2, Day 85)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duvakitug serum concentrations: Ctrough	Ctrough: Serum concentration observed just before treatment administration during multiple dosing	At Treatment Period 2, from Day 1 to Day 85
tmax of CYP substrates alone and after duvakitug administration	tmax: Time to reach Cmax	At Treatment Period 1 (CYP substrates alone, Day 1) and after 12 weeks of duvakitug (Treatment Period 2, Day 85)
t1/2 of CYP substrates alone and after duvakitug administration	Terminal half-life associated with the terminal slope (λz) where λz is the slope of the regression line of the terminal phase of the plasma concentration versus time curve, in semi logarithmic scale. Half-life is calculated by taking the regression of at least 3 points.	At Treatment Period 1 (CYP substrates alone, Day 1) and after 12 weeks of duvakitug (Treatment Period 2, Day 85)
tlast of CYP substrates alone and after duvakitug administration	tlast: Time corresponding to the last concentration above the limit of quantification, Clast	At Treatment Period 1 (CYP substrates alone, Day 1) and after 12 weeks of duvakitug (Treatment Period 2, Day 85)
Cmax of CYP substrates alone and after duvakitug administration	Cmax: Maximum plasma concentration observed	At Treatment Period 1 (CYP substrates alone, Day 1) and after 12 weeks of duvakitug (Treatment Period 2, Day 85)
Number of participants with anti-drug antibodies against duvakitug		At Treatment Period 2, from Day 1 to Day 85
Number of participants with TEAEs, TESAEs, TEAESIs, and TEAEs leading to permanent study intervention discontinuation	TEAE: treatment-emergent adverse event, TESAE: treatment-emergent serious adverse event, TEAESI: treatment-emergent adverse event of special interest	From Treatment Period 1, Day 1 until the End of Study visit (approximately 130 days)

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Teva Branded Pharmaceutical Products R&D LLC

Study record dates

Study Major Dates

• Study Start (Estimated): November 3, 2026
• Primary Completion (Estimated): August 8, 2028
• Study Completion (Estimated): August 29, 2028

Study Registration Dates

• First Submitted: November 2, 2026
• First Submitted That Met QC Criteria: November 2, 2026
• First Posted (Actual): November 6, 2026

Study Record Updates

• Last Update Posted (Actual): November 6, 2026
• Last Update Submitted That Met QC Criteria: November 2, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Keywords: Colitis ulcerative
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative; Crohn Disease
• Other Study ID Numbers: INT20164; 2026-525939-17 (Registry Identifier: CTIS (EU)); U1111-1332-7822 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No