A Study to Assess the Effects of Nemolizumab on Cytochrome P450 Substrates in Participants With Moderate-to-Severe Atopic Dermatitis

Galderma

Status and phase: Completed; Phase 2

Conditions: Atopic Dermatitis

Treatments: Drug: CYP 450 Substrates; Drug: Nemolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04562116

RD.06.SPR.201593

Details and patient eligibility

About

The purpose of this study is to evaluate the effect of nemolizumab (CD14152) on the pharmacokinetics (PK) of a drug "cocktail" representative of CYP450 (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4/5 sensitive index substrates) in adult participants with moderate to- severe atopic dermatitis (AD).

Enrollment: 17 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Chronic atopic dermatitis (AD) for at least 2 years before the screening visit, and confirmed according to American Academy of Dermatology Consensus Criteria at the time of the screening visit
• Eczema Area and Severity Index (EASI) score greater than or equal to (>=) 16 at both the screening and baseline visits
• IGA score >= 3 (based on the Investigator's Global Assessment [IGA] scale ranging from 0 to 4, in which 3 is moderate and 4 is severe) at both the screening and baseline visits
• AD involvement >=10 percent (%) of body surface area (BSA) at both the screening and baseline visits
• Peak (maximum) pruritus numeric rating scale (PP NRS) score of at least 4.0 at both the screening and baseline visit
• Documented recent history (within 6 months before the screening visit) of inadequate response to topical medications (topical corticosteroid [TCS] with or without topical calcineurin inhibitor [TCI])

Exclusion criteria

• Body weight less than (<) 45 kilogram (kg)
• Participants meeting 1 or more of the following criteria at screening or baseline: (a) Had an exacerbation of asthma requiring hospitalization in the preceding 12 months; (b) Reporting asthma that has not been well-controlled in the previous 3 months; (c) Asthma Control Test (ACT) <= 19 (for those with a history of asthma); (d) Peak expiratory flow < 80% of the predicted value
• Participants with a current medical history of chronic obstructive pulmonary disease and/or chronic bronchitis
• Cutaneous infection within 1 week prior to the baseline visit, any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics or antifungals within 2 weeks prior to the baseline visit, or any confirmed or suspected coronavirus disease (COVID)-19 infection within 2 weeks before the screening or baseline visit. Participants may be rescreened once the infection has resolved. Resolution of COVID-19 infection can be confirmed by recovery assessment methods
• Requiring rescue therapy for AD during the screening period or expected to require systemic rescue therapy during the treatment period
• Positive serology results (hepatitis B surface antigen [HBsAg] or hepatitis B core antibody [HBcAb], hepatitis C antibody, or human immunodeficiency virus antibody) at the screening visit
• Treatment with systemic immunosuppressive/immunomodulating drugs and/or systemic corticosteroid within 4 weeks prior to Screening
• Known active or latent tuberculosis
• Treatment with Biologics and their biosimilars within 8 weeks from Screening
• Use of Phototherapy or tanning beds within 4 weeks from Screening
• Use of medication known as inducer, inhibitor, or competitive substrate of one or more of the following cytochrome (CYP) enzymes: CYP3A4/5, CYP2C19, CYP2C9, CYD2D6, and CYP1A2 within 2 weeks from Screening
• Treatment with Midazolam, Omeprazole, Warfarin Sodium, Metoprolol Tartrate within 2 weeks from Screening
• History of hypersensitivity or intolerance to CYP substrates and their excipients
• Participants for whom administration of the CYP substrates provided in this study is contraindicated or medically inadvisable
• Participants with international normalized ratio (INR) > 1.5
• Consumption of any 1 or more of the following food items and/or beverages within 1 week prior to baseline: Grapefruit or grapefruit juice, apple or apple juice, orange or orange juice, lemons or lemon juice, limes or lime juice, cranberries or cranberry juice; Vegetables from the mustard green family (eg, broccoli, kale); Charbroiled meats; Beverages, foods, or drugs containing caffeine
• History of or current confounding skin condition
• Current smokers

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

17 participants in 1 patient group

CYP 450 Substrates plus Nemolizumab

Experimental group

Description:

Participants will receive 1 single oral dose of selected, commercially available, cytochrome P450 substrates (CYP450-S) on Day 1 and after a 1-week washout period, participants will receive a 60 milligram (mg) loading dose of nemolizumab via 2 consecutive subcutaneous (SC) 30-mg injections at the Week 1 visit, followed by a single 30-mg injection once in every 4 weeks (Q4W) at Week 5 and Week 9. Participants will receive a second oral dosing of CYP450-S at Week 10.

Treatment:

Drug: Nemolizumab

Drug: CYP 450 Substrates