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

Phase 2

Completed

Conditions: Atopic Dermatitis

Interventions: Drug: Nemolizumab
Drug: CYP 450 Substrates

Registration Number: NCT04562116

Lead Sponsor: Galderma R&D

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 17

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CYP 450 Substrates plus Nemolizumab	CYP 450 Substrates	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.
CYP 450 Substrates plus Nemolizumab	Nemolizumab	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.

Primary Outcome Measures

Name	Time	Method
Change in Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment	Baseline (before nemolizumab injection, at Week 0) and Week 10 (after nemolizumab injection): Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 72 and 120 hours post-dose	AUC (0-infinity) was defined as AUC from time 0 to infinity, calculated as the sum of AUC (0-last) and C(last)/lambda(z); where C(last) was the last observed measurable (non-BQL) concentration; and lambda(z) was apparent terminal elimination rate constant. Probe drugs included Caffeine, Metoprolol Tartrate, Midazolam, Omeprazole and Warfarin Sodium. Change in AUC(0-infinity) of each of the 5 probe drugs before (Baseline) and after 9-week nemolizumab treatment is reported.
Change in Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC [0-last]) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment	Baseline (before nemolizumab injection, at Week 0) and Week 10 (after nemolizumab injection): Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 72 and 120 hours post-dose	AUC (0-last) was defined as AUC from time 0 to the time of the last measurable (non-BQL) concentration, calculated by linear-linear trapezoidal summation. Probe drugs included Caffeine, Metoprolol Tartrate, Midazolam, Omeprazole and Warfarin Sodium. Change of AUC(0-last) of each of the 5 probe drugs before (Baseline) and after 9-week nemolizumab treatment is reported.
Maximum Observed Plasma Concentration (Cmax) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment	Baseline (before nemolizumab injection, at Week 0) and Week 10 (after nemolizumab injection): Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 72 and 120 hours post-dose	Cmax was defined as the maximum observed plasma concentration. Probe drugs included Caffeine, Metoprolol Tartrate, Midazolam, Omeprazole and Warfarin Sodium. Cmax of each of the 5 probe drugs before (Baseline) and after 9-week nemolizumab treatment is reported.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (TEAEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs)	Up to 24 weeks	An AE is defined as any untoward medical occurrence in a study participant administered a medicinal product which does not necessarily have a causal relationship with this treatment. SAE is any untoward medical occurrence that at any dose may results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. A TEAE is defined as an AE that occurs on or after the first date of study drug(s) administration until the date of last study visit. An AESI is a noteworthy treatment-emergent event for the study drug that should be monitored closely and reported promptly.

Trial Locations

Locations (6): 8894 Galderma Investigational Site
🇺🇸
North Hollywood, California, United States
9954 Galderma Investigational Site
🇺🇸
Hallandale Beach, Florida, United States
9923 Galderma Investigational Site
🇺🇸
Miami, Florida, United States
8030 Galderma Investigational Site
🇺🇸
Raleigh, North Carolina, United States
8076 Galderma Investigational Site
🇺🇸
Austin, Texas, United States
5952 Galderma Investigational Site
🇧🇬
Sofia, Bulgaria
8894 Galderma Investigational Site
🇺🇸North Hollywood, California, United States