An Open-label Drug-Drug Interaction Study to Assess the Effects ofNemolizumab on Cytochrome P450 Substrates in Subjects with Moderate-to-Serve Atopic Dermatitis
- Conditions
- Moderate-to-severe atopic dermatitisMedDRA version: 21.1Level: LLTClassification code 10003639Term: Atopic dermatitisSystem Organ Class: 100000004858Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- EUCTR2020-000229-24-BG
- Lead Sponsor
- Galderma S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 25
1. Subjects aged = 18 years at the time of screening.
2. Chronic 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.
3. EASI score = 16 at both the screening and baseline visits.
4. IGA score = 3 at both the screening and baseline visits.
5. AD involvement = 10% of body surface area (BSA) at both the screening and baseline visits.
6. Peak (maximum) pruritus numeric rating scale (PP NRS) score of at least 4.0 at both the screening and baseline visit.
7. Documented recent history (within 6 months before the screening visit) of inadequate response to topical medications (TCS with or without TCI). All subjects must demonstrate inadequate response to TCS. All
subjects who have used TCI within 6 months of the screening visit must
also demonstrate inadequate response to TCI. Acceptable documentation
includes subject records with information on TCS (with or without TCI)
prescription and treatment outcome, or written documentation of the
conversation with the subject's treating physician, if different than the
investigator. If documentation is inadequate, subjects may be
rescreened after such documentation is obtained.
8. Agree to apply a moisturizer throughout the study from the screening visit; for subjects using stable topical background therapy (TCS ± TCI) at screening, agree to apply topical therapy from the screening visit and throughout the study as determined appropriate by the investigator.
9. Female subjects of childbearing potential must agree to use an adequate and approved non-hormonal method of contraception throughout the study and for 12 weeks after the last study drug injection.
10. Female subjects of non-childbearing potential must meet one of the following criteria:
• Absence of menstrual bleeding for 1 year prior to screening without any other medical reason
• Documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 3 months before screening.
Note: Bilateral tubal ligation is not accepted as reason for non-childbearing potential
11. Subject willing and able to comply with all of the time commitments and procedural requirements of the clinical study protocol.
12. Medically healthy on the basis of medical history, physical examination, renal and hepatic functions. Clinical laboratory test results should be within the laboratory normal range or, if outside of the laboratory normal range, deemed not clinically significant by the investigator or qualified designee.
13. Understand and sign an informed consent form (ICF) before any investigational procedure(s) are performed.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5
1. Body weight < 45 kg
2. Subjects 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 (i.e., symptoms occurring on > 2 days per week, night-time awakenings 2 or more times per week, or some interference with normal activities) during the preceding 3 months.
c. Asthma Control Test (ACT) = 19 (only for subjects with a history of asthma)
d. Peak expiratory flow < 80% of the predicted value.
3. Subjects with a current medical history of chronic obstructive pulmonary disease and/or chronic bronchitis.
4. 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. Subjects may be rescreened once the infection has resolved. Resolution of COVID-19 infection can be confirmed by recovery assessment methods.
5. Requiring rescue therapy for AD during the screening period or expected to require systemic rescue therapy during the treatment period.
6.Positive serology results (hepatitis B surface antigen [HBsAg] or hepatitis B core antibody [HBcAb], hepatitis C [HCV] antibody with positive HCV RNA, or human immunodeficiency virus [HIV] antibody) at the screening visit.
Note: Subjects with a positive HBcAb and a negative HBsAg can be included in this clinical study if hepatitis B surface antibody is positive (considered immune after a natural infection). Subjects who are positive for HCV antibody and negative for HCV RNA may be enrolled.
7. Having received any of the protocol-specified treatments within the specified timeframe before the baseline visit.
8. Previous treatment with nemolizumab.
9. Pregnant women, breastfeeding women, or women planning a pregnancy during the clinical study.
10. History of lymphoproliferative disease or history of malignancy of any organ system within the last 5 years, except for 1) basal cell carcinoma, squamous cell carcinoma in situ (Bowen’s disease), or carcinoma in situ of the cervix that have been treated and have no evidence of recurrence in the last 12 weeks before the screening visit, or 2) actinic keratosis that have been treated.
11. History of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody) or to any of the study drug excipients.
12. History of hypersensitivity or intolerance to CYP substrates and their excipients.
13. Poor metabolizers for CYP2C9, CYP2C19, or CYP2D6 based on genotyping
14. Subjects for whom administration of the CYP substrates provided in this study is contraindicated or medically inadvisable, in the investigator’s judgment, and according to local label of the products
15. 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
Subjects who are not willing to abstain from the consumption of these food items and/or beverages for 7 days before a
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to evaluate the effect of nemolizumab (CD14152) on the<br>pharmacokinetics (PK) of a drug cocktail representative of Cytochrome P450<br>(CYP) 1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4/5 sensitive index<br>substrates in adult subjects with moderate-to-severe atopic dermatitis (AD).;Secondary Objective: The secondary objective is to assess the safety of nemolizumab.;Primary end point(s): The primary endpoint(s) include:<br>• Change of PK parameters (AUC0-inf, AUC0-last and Cmax) in the 5 probe drugs administered concomitantly [Caffeine, Warfarin Sodium, Omeprazole, Metoprolol Tartrate, and Midazolam] derived from the plasma concentration-time profile before and after 9-week nemolizumab treatment.<br>;Timepoint(s) of evaluation of this end point: Visit 2 (Days 1, 2, 4 and 6) and Visit 6 (Days 71, 72, 74 and 76).
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Secondary endpoint(s) include:<br>• Incidence and severity of AEs, including TEAEs, AESIs, and SAEs.<br>;Timepoint(s) of evaluation of this end point: Throughout the study.