Moderate-to-Severe Atopic Dermatitis MedDRA version: 21.1 Level: LLT Classification code 10003639 Term: Atopic dermatitis System Organ Class: 100000004858
Conditions
Sponsors
Galderma S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects aged = 18 years at the screening visit. 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 = 20 at both the screening and baseline visits. Subjects with an EASI score of 18-19 at the screening visit only may be reevaluated once within 48 hours. 4. IGA score = 3 (based on the IGA scale ranging from 0 to 4, in which 3 is moderate and 4 is severe) at both the screening and baseline visits. 5. AD involvement = 10% of BSA at both the screening and baseline visits. 6. PP NRS score of at least 4.0 at the screening and baseline visit. The screening PP NRS score will be determined by a single PP NRS assessment (score ranging from 0 to 10) for the 24-hour period immediately preceding the screening visit. The baseline PP NRS score will be determined based on the average of the daily PP NRS scores (score ranging from 0 to 10) during the 7 days immediately preceding baseline (rounding is not permitted). A minimum of 4 daily scores out of the 7 days immediately preceding baseline is required for this calculation. 7. Documented history of one of the following: a. Previously exposed to CsA: 1) Inadequate response to CsA with previous exposure (defined as flare of AD during CsA tapering from a maximum of 6 weeks of high dose [5 mg/kg/day] to maintenance dose [2 to 3 mg/kg/day] or a flare after a minimum of 3 months on maintenance dose). Flare is defined as increase in signs and/or symptoms leading to escalation of therapy (ie, increase in dose, switch to a higher-potency TCS, or start of another systemic nonsteroidal immunosuppressive drug). or 2) Previous requirement for CsA at doses > 5 mg/kg/day, or duration beyond those specified in the prescribing information (> 1 year). or 3) Intolerance and/or unacceptable toxicity (eg, elevated creatinine, elevated liver function tests, uncontrolled hypertension, paresthesia, headache, nausea, hypertrichosis) with previous CsA exposure. b. CsA is medically inadvisable: 1) medical contraindications (e.g. uncontrolled hypertension on medication). or 2) use of prohibited concomitant medications (e.g. statins, digoxin, macrolide antibiotics, barbiturates, anti-seizure drugs, nonsteroidal anti-inflammatory drugs, diuretics, angiotensin-converting-enzyme inhibitors, St John’s Wort, etc.). or 3) increased susceptibility to CsA-induced renal damage (elevated creatinine) and/or liver damage (elevated function tests). or 4) increased risk of serious infections. or 5) hypersensitivity to CsA active substance or excipients.
Exclusion criteria
Exclusion criteria: 1.Body weight 2 days per week, nighttime 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 (PEF) 19 at screening 3. Current medical history of chronic obstructive pulmonary disease and/or chronic bronchitis. 4. Cutaneous infection within 1 week before the baseline visit, any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics or antifungals within 2 weeks before the baseline visit, or any confirmed or suspected coronavirus disease 2019 (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 can be confirmed by recovery assessment methods, as described in the protocol. Note: Subjects with chronic, stable use of prophylactic treatment for recurrent herpes viral infection can be included in this clinical study. 5. 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 if the 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. In the event of rescreening, the serology tests results (eg, HBV, HCV, HIV) from the first screening can be used by the investigator to assess the eligibility of rescreened subjects if those tests were performed within 6 weeks prior to the baseline visit. 6. Current active or latent tuberculosis (TB) infection or history of either untreated or inadequately treated active or latent TB according to the local applicable guidelines. Note: Subjects who have a documented history of completion of an appropriate TB treatment regimen for latent or active TB with no history of re-exposure to TB since their treatment was completed are eligible to participate in the study. In the event of rescreening, the TB test results from the first screening can be used by the investigator to assess the eligibility of rescreened subjects if the test was performed within 6 weeks prior to the baseline visit. 7. Known or suspected immunosuppression or unusually frequent, recurrent, severe, or prolonged infections as per investigator judgment. 8. 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 carcinomas in situ of the cervix that have been treated and have no evidence of recurrence in the last 12 weeks before the baseline visit, or (2) actinic keratoses that have been treated. 9. Presence of confounding skin conditions that may interfere
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to investigate the efficacy of nemolizumab administered in combination with topical background therapy (topical corticosteroids [TCS] with or without topical calcineurin inhibitors [TCI]) in adult subjects with moderate-to-severe atopic dermatitis (AD) who are not adequately controlled with or are not advised to use oral cyclosporine A (CsA) for medical reasons.;Secondary Objective: The secondary objective is to investigate the safety of nemolizumab in adult subjects with moderate-to-severe AD who are not adequately controlled with or are not advised to use oral CsA for medical reasons.;Primary end point(s): Proportion of subjects with EASI-75 (= 75% improvement in EASI from baseline) at Week 16 Proportion of subjects with an improvement of PP NRS = 4 at Week 16;Timepoint(s) of evaluation of this end point: Week 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Percent change from baseline in EASI at each visit through Week 16 • Proportion of subjects with at least 50%, 75%, or 90% improvement from baseline in EASI (EASI-50, EASI-75, and EASI-90) at each visit through Week 16. • Percent change from baseline in PP NRS at each visit through Week 16. • Proportion of subjects with an improvement of PP NRS = 4 at Week 1, Week 2, and each visit through Week 16. • Proportion of subjects with PP NRS < 2 at each visit through Week 16. • Proportion of subjects with an Investigator Global Assessment (IGA) success (defined as an IGA of 0 [clear] or 1 [almost clear] and a = 2-point reduction from baseline) at each visit through Week 16. • Proportion of subjects with EASI-75 and improvement of PP NRS = 4 at each visit through Week 16. • Proportion of subjects with IGA success and improvement of PP NRS = 4 at each visit through Week 16. • Proportion of subjects with an improvement of sleep disturbance NRS (SD NRS) = 4 at each visit through Week 16. • Percent change from baseline in SD NRS at each visit through Week 16. • Percent change from baseline in SCORing Atopic Dermatitis (SCORAD) and its components at each visit through Week 16. • Change from baseline in percent of body surface area (BSA) affected by AD at each visit through Week 16. • Proportion of subjects with prior CsA use achieving EASI-75 at each visit through Week 16. • Change from baseline in individual components of the EASI (averaged across body regions) at each visit through Week 16. • Change from baseline in AD-associated pain frequency through Week 16. • Change from baseline in AD-associated pain intensity through Week 16. • Incidence of rescue therapy use through Week 16. • Change from baseline in percentage of itch-free days (based on PP NRS = 0/1) through Week 16;Timepoint(s) of evaluation of this end point: Week 16 | — |
Countries
Spain
Contacts
Public ContactClinical Trial Information Desk
Galderma S.A.
Outcome results
None listed