A Study to Assess the Effects of Nemolizumab on Cytochrome P450 Substrates in Participants With Moderate-to-Severe Atopic Dermatitis
Study Details
Study Description
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 moderateto- severe atopic dermatitis (AD).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| 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:
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.
|
Outcome Measures
Primary Outcome Measures
- 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 [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']
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.
- 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 [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']
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.
- Maximum Observed Plasma Concentration (Cmax) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment [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']
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.
Secondary Outcome Measures
- Incidence of Adverse Events (AEs) [Up to 24 weeks]
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.
- Severity of Adverse Events (AEs) [Up to 24 weeks]
The severity of AEs including TEAEs, AESIs, and SAEs will be assessed as mild, moderate or severe.
Eligibility Criteria
Criteria
Inclusion Criteria:
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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
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Eczema Area and Severity Index (EASI) score greater than or equal to (>=) 16 at both the screening and baseline visits
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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
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AD involvement >=10 percent (%) of body surface area (BSA) at both the screening and baseline visits
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Peak (maximum) pruritus numeric rating scale (PP NRS) score of at least 4.0 at both the screening and baseline visit
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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:
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Body weight less than (<) 45 kilogram (kg)
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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
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Participants with a current medical history of chronic obstructive pulmonary disease and/or chronic bronchitis
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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
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Requiring rescue therapy for AD during the screening period or expected to require systemic rescue therapy during the treatment period
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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
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Treatment with systemic immunosuppressive/immunomodulating drugs and/or systemic corticosteroid within 4 weeks prior to Screening
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Known active or latent tuberculosis
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Treatment with Biologics and their biosimilars within 8 weeks from Screening
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Use of Phototherapy or tanning beds within 4 weeks from Screening
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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
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Treatment with Midazolam, Omeprazole, Warfarin Sodium, Metoprolol Tartrate within 2 weeks from Screening
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History of hypersensitivity or intolerance to CYP substrates and their excipients
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Participants for whom administration of the CYP substrates provided in this study is contraindicated or medically inadvisable
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Participants with international normalized ratio (INR) > 1.5
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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
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History of or current confounding skin condition
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Current smokers
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 8894 Galderma Investigational Site | North Hollywood | California | United States | 91606 |
| 2 | 8310 Galderma Investigational Site | Tustin | California | United States | 92780 |
| 3 | 9954 Galderma Investigational Site | Hallandale Beach | Florida | United States | 33009 |
| 4 | 9923 Galderma Investigational Site | Miami | Florida | United States | 33147 |
| 5 | 8030 Galderma Investigational Site | Raleigh | North Carolina | United States | 27612 |
| 6 | 8076 Galderma Investigational Site | Austin | Texas | United States | 78759 |
| 7 | 5952 Galderma Investigational Site | Sofia | Bulgaria | 1612 |
Sponsors and Collaborators
- Galderma R&D
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RD.06.SPR.201593