Clinical trial NCT04562116: A Study to Assess the Effects of Nemolizumab on Cytochrome P450 Substrates in Participants With Moderate-to-Severe Atopic Dermatitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atopic Dermatitis
Lead sponsor: Galderma R&D
Sponsor class: INDUSTRY
First posted: 2020-09-24
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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).


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment
timeFrame: 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:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs)
timeFrame: Up to 24 weeks
Other outcomes:
Locations:
city: North Hollywood
country: United States
facility: 8894 Galderma Investigational Site
state: California
city: Hallandale Beach
country: United States
facility: 9954 Galderma Investigational Site
state: Florida
city: Miami
country: United States
facility: 9923 Galderma Investigational Site
state: Florida
city: Raleigh
country: United States
facility: 8030 Galderma Investigational Site
state: North Carolina
city: Austin
country: United States
facility: 8076 Galderma Investigational Site
state: Texas
city: Sofia
country: Bulgaria
facility: 5952 Galderma Investigational Site
Study officials:
References: