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

An Open-label Drug-Drug Interaction Study to Assess the Effects of Nemolizumab on Cytochrome P450 Substrates in Subjects With Moderate-to-Severe Atopic Dermatitis

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).

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Nemolizumab; Drug: CYP 450 Substrates

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1612
    • 5952 Galderma Investigational Site
• United States
  • California
    • North Hollywood, California, United States, 91606
      • 8894 Galderma Investigational Site
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • 9954 Galderma Investigational Site
    • Miami, Florida, United States, 33147
      • 9923 Galderma Investigational Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • 8030 Galderma Investigational Site
  • Texas
    • Austin, Texas, United States, 78759
      • 8076 Galderma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CYP 450 Substrates plus 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.

Drug: Nemolizumab; Nemolizumab 30 mg will be administered as SC injections.; Other Names: CD14152; Drug: CYP 450 Substrates; CYP substrates (Caffeine, Warfarin Sodium, Midazolam, Omeprazole, and Metoprolol Tartrate) will administered orally at Week 0 (Day 1) and Week 10 as per the commercially available prescribing information.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	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
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	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.	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
Maximum Observed Plasma Concentration (Cmax) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment	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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs)	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.	Up to 24 weeks

Collaborators and Investigators

• Sponsor: Galderma R&D

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2021
• Primary Completion (Actual): June 7, 2023
• Study Completion (Actual): June 7, 2023

Study Registration Dates

• First Submitted: September 18, 2020
• First Submitted That Met QC Criteria: September 18, 2020
• First Posted (Actual): September 24, 2020

Study Record Updates

• Last Update Posted (Actual): December 5, 2024
• Last Update Submitted That Met QC Criteria: November 11, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Skin Diseases, Genetic; Skin Diseases, Eczematous; Dermatitis, Atopic; Dermatitis; Eczema
• Other Study ID Numbers: RD.06.SPR.201593

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No