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

NCT06686628 | Completed Phase 1

• 3 other identifiers: INT18404U1111-1303-34062024-513495-17
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single group, 2-period, Phase 1, single-sequence study. The study duration will be up to 342 days. The treatment period will be up to Week 29, where Week 29 is defined as End of Treatment (last amlitelimab administration at Week 25). The number of visits will be 23 or 21 visits for participants who decide to continue amlitelimab therapy in the long-term extension study LTS17367 (RIVER-AD) study.

Conditions

Dermatitis Atopic

Outcome Measures

Primary Outcomes (1)

• AUC and AUClast for CYP substrates

  AUC = area under the serum/plasma concentration curve; AUClast = area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast.

  Baseline (Day 1 to Day 8) and Day 176 to Day 183

Secondary Outcomes (5)

• Incidence of treatment-emergent adverse events, serious adverse events, adverse event of special interest, and potentially clinically significant abnormality.

  Baseline through Day 316

• Serum amlitelimab concentrations (Ctrough) measured.

  Day 8 through Day 316

• Tmax, t1/2z, and tlast of CYP substrates alone and co-administered with amlitelimab

  Baseline (Day 1 to Day 8) and Day 176 to Day 183

• Cmax of CYP substrates alone and co-administered with amlitelimab

  Baseline (Day 1 to Day 8) and Day 176 to Day 183

• Incidence of anti-drug antibodies of amlitelimab.

  Baseline through Day 316

Study Arms (1)

Amlitelimab and CYP substrates

EXPERIMENTAL

A single oral dose of a CYP450 substrates cocktail which will include caffeine, metoprolol, midazolam, omeprazole, and warfarin will be administered. A single dose of amlitelimab will then be administered on several days. A single oral dose of CYP450 substrates cocktail in combination with the last single dose of amlitelimab.

Drug: Amlitelimab; Drug: Midazolam; Drug: Caffeine; Drug: Metoprolol; Drug: Omeprazole; Drug: Warfarin

Interventions

Amlitelimab DRUG

Pharmaceutical form: Injection solution Route of administration: SC injection

Also known as: SAR445229

Amlitelimab and CYP substrates

Midazolam DRUG

Pharmaceutical form: Solution Route of administration: Oral

Amlitelimab and CYP substrates

Caffeine DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Amlitelimab and CYP substrates

Metoprolol DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Amlitelimab and CYP substrates

Omeprazole DRUG

Pharmaceutical form: Capsule Route of administration: Oral

Amlitelimab and CYP substrates

Warfarin DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Amlitelimab and CYP substrates

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Male or female participant aged 18 to 65 years (inclusive), at the time of the informed consent is signed.
• Participants must have AD as defined by the American Academy of Dermatology Consensus Criteria (2014) for 1 year or longer before signing of informed consent.
• The EASI score ≥16 at Screening and Check-in (Day -1).
• vIGA-AD score ≥3 (on the 0 to 4 vIGA-AD scale) at Screening and Check-in (Day -1).
• AD involvement of ≥10% body surface area at Screening and Check-in (Day -1).
• Participants must have documented history within 6 months prior to Screening and Check-in (Day -1), of either inadequate response (including inadequate efficacy or medical inadvisability) of topical treatments.
• Body weight within 40 to 150 kg at Screening and Day 1 and body mass index (BMI) \<40 kg/m2 (inclusive).
• Capable of giving signed informed consent.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Known history of significant immunosuppression or suspected current significant immunosuppression, including history of invasive opportunistic, or helminthic infections.
• Any malignancies or history of malignancies prior to baseline (except for non-melanoma skin cancer that has been excised and cured for more than 5 years prior to baseline).
• Any concomitant illness that would, in the Investigator's opinion, inhibit the participant's participation in the study, including for example, but not limited to, hypertension, renal disease, neurological conditions, heart failure, and pulmonary disease.
• Any medical condition which, in the Investigator's opinion may present an unreasonable risk to the study participants as a result of his/her participation in this clinical study, may make participant's participation unreliable, or may interfere with study assessments.
• Any active or chronic infection including helminthic infection requiring systemic treatment within 4 weeks prior to baseline (1 week in the event of superficial skin infections) and any infection which as per Investigator's opinion precludes the participant's participation in the study or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals at Screening or Check--in (Day -1).
• History or presence of substance abuse (including alcohol, nicotine) prior to Check-in (Day 1/V2) or regular alcohol consumption (\>14 units per week for males and \>7 units per week for females).
• In the Investigator's opinion, medical conditions related to prior AD medications that have not healed/fully recovered for more than 2 weeks before the Screening visit, including, but not limited to, conjunctivitis, keratitis, eosinophilic conditions, arthralgia, herpes zoster, thrombosis.
• Use of tobacco- or nicotine-containing products within 6 months prior to Check-in (Day -1).
• Poor metabolizers for CYP2C9, CYP2C19, or CYP2D6 based on genotyping.
• Treatment with a live (attenuated) vaccine within 12 weeks prior to baseline; failure to complete non-live immunization required by local regulation (eg, vaccination for COVID-19) at least 14 days prior to baseline.
• Any contraindication to one or more of the following CYP cocktail study interventions, according to the applicable labeling:
• Caffeine
• Metoprolol
• Midazolam

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Investigational Site Number : 2760001

Berlin, 10117, Germany

Location

Related Links

• INT18404 Plain Language Results Summary

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

Midazolam; Caffeine; Metoprolol; Omeprazole; Warfarin

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Xanthines; Alkaloids; Purinones; Purines; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Benzimidazoles; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2024
• First Posted: November 13, 2024
• Study Start: November 20, 2024
• Primary Completion: November 21, 2025
• Study Completion: April 2, 2026
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)