Clinical trial NCT05056779: Efficacy and Safety of Nemolizumab in Subjects With Moderate-to-Severe Atopic Dermatitis With Inadequate Response to or for Whom Cyclosporine A is Not Medically Advisable
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Nemolizumab in Subjects With Moderate-to-Severe Atopic Dermatitis With Inadequate Response to or for Whom Cyclosporine A is Not Medically Advisable
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Moderate-to-severe Atopic Dermatitis
Lead sponsor: Galderma R&D
Sponsor class: INDUSTRY
First posted: 2021-09-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study 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 participants 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. The secondary objective is to investigate the safety of nemolizumab in adult participants with moderate-to-severe AD who are not adequately controlled with or are not advised to use oral CsA for medical reasons.

The study will be carried out in up to 70 different locations across Europe.


Eligibility criteria: Inclusion Criteria:

1. Chronic AD for at least 2 years before the screening visit and confirmed according to American Academy of Dermatology Consensus at the time of the screening visit.
2. EASI score ≥ 20 at both the screening and baseline visits. Participant with an EASI score of 18-19 at the screening visit only may be reevaluated once within 48 hours.
3. 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.
4. AD involvement ≥ 10% of BSA at both the screening and baseline visits.
5. Documented history by a physician (within 6 months before the screening visit) of inadequate response to topical medications or use of systemic therapies for control of the disease.
6. Agree to apply a moisturizer throughout the study from the screening visit; agree to apply an authorized TCS, with or without TCI, from the screening visit and throughout the study as determined appropriate by the investigator.
7. Documented history of one of the following, where CsA treatment should not be continued/restarted or participant is not currently a candidate for CsA treatment:

   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 topical corticosteroids \[TCS\] 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)
   3. Intolerance and/or unacceptable toxicity (eg, elevated creatinine, elevated liver function tests, uncontrolled hypertension, paresthesia, headache, nausea, hypertrichosis) with previous CsA exposure
   4. CsA is medically inadvisable due to medical contraindication, use of prohibited medications, risk of AEs (eg, serious infection) or toxicity (eg, renal or liver damage), or hypersensitivity to CsA or excipients, in the opinion of the investigator

   Acceptable documentation includes patient records with information on CsA prescription and treatment outcome, other prohibitive medications/medical history, or written documentation of the conversation with the participant's treating physician, if different than the investigator, as applicable.
8. Other protocol defined inclusion criteria could apply.

Exclusion Criteria:

1. Body weight \< 30 kg.
2. One or more of the following criteria at screening or baseline:

   1. Exacerbation of asthma requiring hospitalization in the preceding 12 months.
   2. Asthma that has not been well controlled (i.e, symptoms occurring on \> 2 days per week, nighttime awakenings 2 or more times per week, or some interference with normal activities) during the preceding 3 months.
   3. Asthma Control Test (ACT) ≤ 19 (only for subjects with a history of asthma).
   4. Peak expiratory flow (PEF) \< 80% of the predicted value.
3. Current medical history of chronic obstructive pulmonary disease and/or chronic bronchitis.
4. 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.
5. Presence of confounding skin conditions that may interfere with study assessments.
6. Planned or expected major surgical procedure during the clinical study.
7. Other protocol defined exclusion criteria could apply.

Primary outcomes:
measure: Proportion of Participants with Eczema Area and Severity Index-75 (EASI-75) (≥ 75% Improvement in EASI from Baseline) at Week 16
timeFrame: Week 16
measure: Proportion of Participants with an Improvement of Peak Pruritus Numeric Rating Scale (PP NRS) ≥ 4 at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Percent Change from Baseline in EASI at Each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Proportion of Participants with at Least 50%, 75%, or 90% Improvement from Baseline in Eczema Area and Severity Index (EASI-50, EASI-75, and EASI-90) at Each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Percent Change From Baseline in Peak Pruritus Numeric Rating Scale (PP NRS) at Each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Proportion of Participants with an Improvement of Peak Pruritus Numeric Rating Scale (PP NRS) ≥ 4 at Week 1, Week 2, and Each Visit Through Week 16
timeFrame: From Week 1 to Week 16
measure: Proportion of Participants with Peak Pruritus Numeric Rating Scale (PP NRS) < 2 at each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Proportion of Participants with an Investigator's 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
timeFrame: Baseline through week 16
measure: Proportion of Participants with EASI-75 and improvement of PP NRS ≥ 4 at Each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Proportion of Participants with IGA Success and Improvement of PP NRS ≥ 4 at each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Proportion of Participants with an Improvement of Sleep Disturbance Numeric Rating Scale (SD NRS) ≥ 4 at Each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Percent Change from Baseline in Sleep Disturbance Numeric Rating Scale (SD NRS) at Each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Percent Change from Baseline in SCORing Atopic Dermatitis (SCORAD) and It's Components at Each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Change from Baseline in Percent of Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Proportion of Participants with Prior Cyclosporine A (CsA) Use Achieving EASI-75 at Each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Change from Baseline in Individual Components of the EASI (Averaged Across Body Regions) at Each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Change from Baseline in Atopic Dermatitis (AD)-Associated Pain Frequency Through Week 16
timeFrame: Baseline through week 16
measure: Change from Baseline in Atopic Dermatitis (AD)-Associated Pain Intensity Through Week 16
timeFrame: Baseline through week 16
measure: Incidence of Rescue Therapy Use Through Week 16
timeFrame: Baseline through week 16
measure: Change from Baseline in Percentage of Itch-Free Days (Based on PP NRS = 0/1) Through Week 16
timeFrame: Baseline through week 16
measure: Change from Baseline in Dermatology Life Quality Index (DLQI) Total Score at Each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Change from Baseline in Patient-Oriented Eczema Measure (POEM) Total Score at Each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Number of Days Free of Topical Atopic Dermatitis (AD) Therapy From Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Change from baseline in Hospital Anxiety and Depression Scale (HADS) for each subscale (ie, depression and anxiety) at each visit through Week 16
timeFrame: Baseline through week 16
measure: Proportion of Participants Reporting Hospital Anxiety and Depression Scale (HADS) anxiety Scores < 8 for those Reporting Scores ≥ 8 at Baseline at Each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Proportion of Participants Reporting HADS depression Scores < 8 for Those Reporting Scores ≥ 8 at Baseline at Each Visit Through Week 16
timeFrame: Baseline through week 16
measure: Change from Baseline in EuroQoL 5-Dimension (EQ-5D) at each visit through Week 16
timeFrame: Baseline through week 16
measure: Incidence and Severity of Adverse Events (AEs), Including Adverse Events of Special Interest (AESIs), Treatment Emergent AEs (TEAEs), and serious AEs (SAEs)
timeFrame: Baseline through week 24
Other outcomes:
Locations:
Study officials:
References: