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

NCT04562116 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: RD.06.SPR.201593
• Study Type: interventional
• Target: 17
• Locations: 2 countries
• Sites: 6

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).

Conditions

Atopic Dermatitis

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs)

  Up to 24 weeks

Study Arms (1)

CYP 450 Substrates plus Nemolizumab

EXPERIMENTAL

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; Drug: CYP 450 Substrates

Interventions

Nemolizumab DRUG

Nemolizumab 30 mg will be administered as SC injections.

Also known as: CD14152

CYP 450 Substrates plus Nemolizumab

CYP 450 Substrates DRUG

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.

CYP 450 Substrates plus Nemolizumab

Eligibility Criteria

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

You may qualify if:

• 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 \[TCI\])

You may not qualify if:

• 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

Sponsors & Collaborators

• Galderma R&D: lead

Study Sites (6)

8894 Galderma Investigational Site

North Hollywood, California, 91606, United States

Location

9954 Galderma Investigational Site

Hallandale, Florida, 33009, United States

Location

9923 Galderma Investigational Site

Miami, Florida, 33147, United States

Location

8030 Galderma Investigational Site

Raleigh, North Carolina, 27612, United States

Location

8076 Galderma Investigational Site

Austin, Texas, 78759, United States

Location

5952 Galderma Investigational Site

Sofia, 1612, Bulgaria

Location

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

nemolizumab

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

Results Point of Contact

• Title: Clinical Operations
• Organization: Galderma

Clinical.Studies@galderma.com

08179615000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2020
• First Posted: September 24, 2020
• Study Start: December 8, 2021
• Primary Completion: June 7, 2023
• Study Completion: June 7, 2023
• Last Updated: December 5, 2024
• Results First Posted: December 5, 2024

Record last verified: 2024-11

Locations

US (5); BU (1)