Efficacy & Safety of Nemolizumab in Subjects With Moderate-to-Severe Atopic Dermatitis

Phase 3

Completed

Conditions: Moderate-to-Severe Atopic Dermatitis

Interventions: Drug: Placebo
Drug: Nemolizumab

Registration Number: NCT03989349

Lead Sponsor: Galderma R&D

Brief Summary: The main purpose of the study was to assess the efficacy and safety of nemolizumab after a 16-week treatment period in adult and adolescent subjects with moderate-to-severe atopic dermatitis (AD) not adequately controlled with topical treatments.

Detailed Description: This was a randomized, double-blind, placebo-controlled, multi-center, parallel-group study in adult and adolescent subjects of age 12 years and above with moderate-to-severe AD. Eligible subjects had documented history of inadequate response to topical AD medication(s). Approximately 750 subjects were randomized in 2:1 to receive either nemolizumab or placebo, stratified by baseline disease severity (Investigator's Global Assessment (IGA) = 3, moderate; IGA = 4, severe) and peak pruritus numeric rating scale (PP NRS) severity (PP NRS \>= 7; PP NRS \< 7). A minimum of 250 subjects were randomized in each PP NRS strata. All nemolizumab-treated subjects who were clinical responders at Week 16 (i.e., the end of initial treatment \[Initial Treatment Period\]/beginning of Maintenance Period) were re-randomized (1:1:1) to different treatment regimens (nemolizumab injections Q4W or every 8 weeks (Q8W) \[with placebo injections at Weeks 20, 28, 36, and 44 to maintain the blind\] or placebo Q4W). A clinical responder was defined as a subject at Week 16 with an IGA of 0 (clear) or 1 (almost clear) or a \>=75% improvement in EASI from baseline (EASI-75). All placebo-treated subjects who responded to placebo during the Initial Treatment Period continued to receive placebo Q4W in the Maintenance Period.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 787

Inclusion Criteria

Male or female subjects aged greater than and equal to (>=) 12 years at the screening visit.
Chronic atopic dermatitis (according to American Academy of Dermatology Consensus Criteria) that has been present for at least 2 years before the screening visit.
Eczema Area and Severity Index (EASI) score >=16 at the screening and baseline visits.
Investigator Global Assessment (IGA) score >= 3 (scale of 0 to 4) at the screening and baseline visits.
AD involvement >= 10 percent (%) of body surface area (BSA) at screening and baseline visits.
Peak Pruritus Numerical Rating Scale (PPNRS) score of at least 4.0 at the screening and baseline visits.
Documented recent history of inadequate response to topical medications (topical corticosteroids [TCS] with or without Topical calcineurin inhibitors [TCI]).
Female subjects of childbearing potential (that is, fertile, following menarche and until becoming postmenopausal unless permanently sterile) must agree either to be strictly abstinent throughout the study and for 12 weeks after the last study drug injection or to use an adequate and approved method of contraception throughout the study and for 12 weeks after the last study drug injection.

Key

Exclusion Criteria

Body weight (<) 30 kilograms (kg)
Exacerbation of asthma requiring hospitalization in the preceding 12 months. Uncontrolled asthma in the preceding 3 months.
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 (COVID)-19 infection within 2 weeks before the screening or baseline visit.
Pregnant women, breastfeeding women, or women planning a pregnancy during the clinical study.

Note: Subjects with chronic,stable use of prophylactic treatment for recurrent herpes viral infection can be included in this clinical study.

History of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived or recombinant, e.g., monoclonal antibody) or to any of the study drug excipients.
Any clinically significant issue, based on investigator judgement.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo administered via subcutaneous injection
Nemolizumab	Nemolizumab	Nemolizumab administered via subcutaneous injection

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Investigator's Global Assessment (IGA) Success at Week 16: Severe Pruritus Population	Week 16	IGA success was defined as an IGA score of 0 (clear) or 1 (almost clear) and at least a 2-grade improvement from baseline to Week 16. The IGA is a 5-point scale ranging from 0 (clear) to 4 (severe) used by the Investigator or trained designee to evaluate the global severity of AD and the clinical response to treatment. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered a treatment failure. Participants with missing data at Week 16 were considered non-responders.
Percentage of Participants With >=75% Improvement in Eczema Area and Severity Index (EASI-75) at Week 16: ITT Population	Week 16	EASI-75 was defined as \>=75 percent(%) improvement in EASI from baseline to Week 16. EASI evaluates severity of participants AD based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD(erythema, induration/papulation, excoriation and lichenification)scored separately for each of 4 body regions (head \& neck, upper limbs, trunk \& lower limbs on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI total score is composite score ranging from 0 to 72. Higher scores represent greater severity of AD. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered a treatment failure. Participants with missing data at Week 16 were considered non-responders.
Percentage of Participants With >=75% Improvement in Eczema Area and Severity Index (EASI-75) at Week 16: Severe Pruritus Population	Week 16	EASI-75 was defined as \>=75 percent(%) improvement in EASI from baseline to Week 16. EASI evaluates severity of participants AD based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD(erythema, induration/papulation, excoriation and lichenification)scored separately for each of 4 body regions (head \& neck, upper limbs, trunk \& lower limbs on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI total score is composite score ranging from 0 to 72. Higher scores represent greater severity of AD. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered a treatment failure. Participants with missing data at Week 16 were considered non-responders.
Percentage of Participants With Investigator's Global Assessment (IGA) Success at Week 16: Intent-To-Treat (ITT) Population	Week 16	IGA success was defined as an IGA score of 0 (clear) or 1 (almost clear) and at least a 2-grade improvement from baseline to Week 16. The IGA is a 5-point scale ranging from 0 (clear) to 4 (severe) used by the Investigator or trained designee to evaluate the global severity of atopic dermatitis (AD) and the clinical response to treatment. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure. Participants with missing data at Week 16 were considered non-responders.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With an Improvement of Sleep Disturbance Numeric Rating Scale (SD NRS) >=4 at Week 16: Severe Pruritus Population	Week 16	The sleep disturbance NRS is a scale used by the participants to report the degree of their sleep loss related to AD. Participants were asked the following question in their local language: how would you rate your sleep last night? On a scale of 0 to 10, with 0 being 'no sleep loss related to signs/symptoms of AD' and 10 being 'I cannot sleep at all due to the signs/symptoms of AD'. Weekly average SD NRS score was calculated using 7 consecutive days diary data and set to missing if less than 4 days data available. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure. Participants with missing data were considered non-responders.
Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 4: ITT Population	Week 4	The PP NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours on a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable'. Weekly average PP NRS score was calculated using 7 consecutive days diary data and set to missing if less than 4 days data available. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure. Participants with missing data were considered non-responders.
Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 16: ITT Population	Week 16	The PP NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours on a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable'. Weekly average PP NRS score was calculated using 7 consecutive days diary data and set to missing if less than 4 days data available. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure.
Percentage of Participants With <2 Points in Weekly Average PP NRS at Week 16: ITT Population	Week 16	The PP NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours on a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable'. Weekly average PP NRS score was calculated using 7 consecutive days diary data and set to missing if less than 4 days data available. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure. Participants with missing data were considered non-responders.
Percentage of Participants With an Improvement of Sleep Disturbance Numeric Rating Scale (SD NRS) >=4 at Week 16: ITT Population	Week 16	The sleep disturbance NRS is a scale used by the participants to report the degree of their sleep loss related to AD. Participants were asked the following question in their local language: how would you rate your sleep last night? On a scale of 0 to 10, with 0 being 'no sleep loss related to signs/symptoms of AD' and 10 being 'I cannot sleep at all due to the signs/symptoms of AD'. Weekly average SD NRS score was calculated using 7 consecutive days diary data and set to missing if less than 4 days data available. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure. Participants with missing data were considered non-responders.
Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 1: Severe Pruritus Population	Week 1	The PP NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours on a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable'. Weekly average PP NRS score was calculated using 7 consecutive days diary data and set to missing if less than 4 days data available. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure. Participants with missing data were considered non-responders.
Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 16: Severe Pruritus Population	Week 16	The PP NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours on a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable'. Weekly average PP NRS score was calculated using 7 consecutive days diary data and set to missing if less than 4 days data available. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure.
Percentage of Participants With <2 Points in Weekly Average PP NRS at Week 16: Severe Pruritus Population	Week 16	The PP NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours on a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable'. Weekly average PP NRS score was calculated using 7 consecutive days diary data and set to missing if less than 4 days data available. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure. Participants with missing data were considered non-responders.
Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 4: Severe Pruritus Population	Week 4	The PP NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours on a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable'. Weekly average PP NRS score was calculated using 7 consecutive days diary data and set to missing if less than 4 days data available. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure. Participants with missing data were considered non-responders.
Percentage of Participants With Peak Pruritus Numeric Rating Scale (PP NRS) <2 at Week 4: ITT Population	Week 4	The PP NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours on a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable'. Weekly average PP NRS score was calculated using 7 consecutive days diary data and set to missing if less than 4 days data available. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure. Participants with missing data were considered non-responders.
Percentage of Participants With Peak Pruritus Numeric Rating Scale (PP NRS) <2 at Week 4: Severe Pruritus Population	Week 4	The PP NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours on a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable'. Weekly average PP NRS score was calculated using 7 consecutive days diary data and set to missing if less than 4 days data available. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure. Participants with missing data were considered non-responders.
Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 2: ITT Population	Week 2	The PP NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours on a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable'. Weekly average PP NRS score was calculated using 7 consecutive days diary data and set to missing if less than 4 days data available. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure. Participants with missing data were considered non-responders.
Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 2: Severe Pruritus Population	Week 2	The PP NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours on a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable'. Weekly average PP NRS score was calculated using 7 consecutive days diary data and set to missing if less than 4 days data available. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure. Participants with missing data were considered non-responders.
Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 1: ITT Population	Week 1	The PP NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours on a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable'. Weekly average PP NRS score was calculated using 7 consecutive days diary data and set to missing if less than 4 days data available. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure. Participants with missing data were considered non-responders.

Trial Locations

Locations (138): Galderma Investigational Site 8749
🇺🇸
Birmingham, Alabama, United States
Galderma Investigational Site 8893
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Birmingham, Alabama, United States
Galderma Investigational Site 8866
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Guntersville, Alabama, United States
Galderma Investigational Site 8808
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Scottsdale, Arizona, United States
Galderma Investigational Site 8906
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Bell Gardens, California, United States
Galderma Investigational Site 8905
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Canoga Park, California, United States
Galderma Investigational Site 8577
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Encinitas, California, United States
Galderma Investigational Site 8673
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Garden Grove, California, United States
Galderma Investigational Site 8683
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Los Angeles, California, United States
Galderma Investigational Site 8907
🇺🇸
Newport Beach, California, United States
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Galderma Investigational Site 8749
🇺🇸Birmingham, Alabama, United States