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

Atopic Dermatitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04562116
• Other study ID #: RD.06.SPR.201593
• Status: Completed
• Phase: Phase 2
• Start date: May 24, 2021
• Est. completion date: June 7, 2023

Study information

• Verified date: January 2024
• Source: Galderma R&D
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 moderateto- severe atopic dermatitis (AD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: June 7, 2023
• Est. primary completion date: June 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Nemolizumab
Nemolizumab 30 mg will be administered as SC injections.
• 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.

Locations

Country	Name	City	State
Bulgaria	5952 Galderma Investigational Site	Sofia
United States	8076 Galderma Investigational Site	Austin	Texas
United States	9954 Galderma Investigational Site	Hallandale Beach	Florida
United States	9923 Galderma Investigational Site	Miami	Florida
United States	8894 Galderma Investigational Site	North Hollywood	California
United States	8030 Galderma Investigational Site	Raleigh	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Galderma R&D

Countries where clinical trial is conducted

United States,  Bulgaria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of 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	Change of AUC (0-infinity) of each of the 5 probe drugs before and after 9-week nemolizumab treatment will be assessed. AUC (0-infinity) is defined as AUC from time 0 to infinity, calculated as the sum of AUC (0-last) and C(last)/lambda(z); where C(last) is the last observed measurable (non-BQL) concentration; and lambda(z) is apparent terminal elimination rate constant.	Baseline (Week 0) and Week 10: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 72 and 120 hours post-dose'
Primary	Change of 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	Change of AUC (0-last) of each of the 5 probe drugs before and after 9-week nemolizumab treatment will be assessed. AUC (0-last) is defined as AUC from time 0 to the time of the last measurable (non-below quantification limit [non-BQL]) concentration, calculated by linear-linear trapezoidal summation.	Baseline (Week 0) and Week 10: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 72 and 120 hours post-dose'
Primary	Maximum Observed Plasma Concentration (Cmax) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment	Change of Cmax of each of the 5 probe drugs before and after 9-week nemolizumab treatment will be assessed. Cmax is defined as the maximum observed plasma concentration.	Baseline (Week 0) and Week 10: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 72 and 120 hours post-dose'
Secondary	Incidence of Adverse Events (AEs)	Incidence of AEs including treatment emergent AEs (TEAEs), AEs of special interest (AESIs), and serious AEs (SAEs) will be reported. 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
Secondary	Severity of Adverse Events (AEs)	The severity of AEs including TEAEs, AESIs, and SAEs will be assessed as mild, moderate or severe.	Up to 24 weeks