Clinical trial NCT03989349: Efficacy & Safety of Nemolizumab in Subjects With Moderate-to-Severe Atopic Dermatitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Moderate-to-Severe Atopic Dermatitis
Keywords: CD14152
Nemolizumab
Atopic Dermatitis
Lead sponsor: Galderma R&D
Sponsor class: INDUSTRY
First posted: 2019-06-18
Enrollment: 787
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Key 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.

Primary outcomes:
measure: Percentage of Participants With Investigator's Global Assessment (IGA) Success at Week 16: Intent-To-Treat (ITT) Population
timeFrame: Week 16
measure: Percentage of Participants With Investigator's Global Assessment (IGA) Success at Week 16: Severe Pruritus Population
timeFrame: Week 16
measure: Percentage of Participants With >=75% Improvement in Eczema Area and Severity Index (EASI-75) at Week 16: ITT Population
timeFrame: Week 16
measure: Percentage of Participants With >=75% Improvement in Eczema Area and Severity Index (EASI-75) at Week 16: Severe Pruritus Population
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 16: ITT Population
timeFrame: Week 16
measure: Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 16: Severe Pruritus Population
timeFrame: Week 16
measure: Percentage of Participants With <2 Points in Weekly Average PP NRS at Week 16: ITT Population
timeFrame: Week 16
measure: Percentage of Participants With <2 Points in Weekly Average PP NRS at Week 16: Severe Pruritus Population
timeFrame: Week 16
measure: Percentage of Participants With an Improvement of Sleep Disturbance Numeric Rating Scale (SD NRS) >=4 at Week 16: ITT Population
timeFrame: Week 16
measure: Percentage of Participants With an Improvement of Sleep Disturbance Numeric Rating Scale (SD NRS) >=4 at Week 16: Severe Pruritus Population
timeFrame: Week 16
measure: Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 4: ITT Population
timeFrame: Week 4
measure: Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 4: Severe Pruritus Population
timeFrame: Week 4
measure: Percentage of Participants With Peak Pruritus Numeric Rating Scale (PP NRS) <2 at Week 4: ITT Population
timeFrame: Week 4
measure: Percentage of Participants With Peak Pruritus Numeric Rating Scale (PP NRS) <2 at Week 4: Severe Pruritus Population
timeFrame: Week 4
measure: Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 2: ITT Population
timeFrame: Week 2
measure: Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 2: Severe Pruritus Population
timeFrame: Week 2
measure: Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 1: ITT Population
timeFrame: Week 1
measure: Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 1: Severe Pruritus Population
timeFrame: Week 1
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Galderma Investigational Site 8749
state: Alabama
city: Birmingham
country: United States
facility: Galderma Investigational Site 8893
state: Alabama
city: Guntersville
country: United States
facility: Galderma Investigational Site 8866
state: Alabama
city: Scottsdale
country: United States
facility: Galderma Investigational Site 8808
state: Arizona
city: Bell Gardens
country: United States
facility: Galderma Investigational Site 8906
state: California
city: Canoga Park
country: United States
facility: Galderma Investigational Site 8905
state: California
city: Encinitas
country: United States
facility: Galderma Investigational Site 8577
state: California
city: Garden Grove
country: United States
facility: Galderma Investigational Site 8673
state: California
city: Los Angeles
country: United States
facility: Galderma Investigational Site 8683
state: California
city: Newport Beach
country: United States
facility: Galderma Investigational Site 8907
state: California
city: Ontario
country: United States
facility: Galderma Investigational Site 8799
state: California
city: Pasadena
country: United States
facility: Galderma Investigational Site 8745
state: California
city: San Diego
country: United States
facility: Galderma Investigational Site 8658
state: California
city: Santa Ana
country: United States
facility: Galderma Investigational Site 8536
state: California
city: Westminster
country: United States
facility: Galderma Investigational Site 8820
state: California
city: Farmington
country: United States
facility: Galderma Investigational Site 8637
state: Connecticut
city: Delray Beach
country: United States
facility: Galderma Investigational Site 8875
state: Florida
city: Hialeah
country: United States
facility: Galderma Investigational Site 8391
state: Florida
city: Hialeah
country: United States
facility: Galderma Investigational Site 8727
state: Florida
city: Largo
country: United States
facility: Galderma Investigational Site 8523
state: Florida
city: Miami
country: United States
facility: Galderma Investigational Site 8719
state: Florida
city: Miami
country: United States
facility: Galderma Investigational Site 8656
state: Florida
city: Miami
country: United States
facility: Galderma Investigational Site 8704
state: Florida
city: Miami
country: United States
facility: Galderma Investigational Site 8706
state: Florida
city: Tampa
country: United States
facility: Galderma Investigational Site 8203
state: Florida
city: Tampa
country: United States
facility: Galderma Investigational Site 8839
state: Florida
city: Rolling Meadows
country: United States
facility: Galderma Investigational Site 8729
state: Illinois
city: New Albany
country: United States
facility: Galderma Investigational Site 8724
state: Indiana
city: Detroit
country: United States
facility: Galderma Investigational Site 8554
state: Michigan
city: Las Vegas
country: United States
facility: Galderma Investigational Site 8825
state: Nevada
city: Hackensack
country: United States
facility: Galderma Investigational Site 8506
state: New Jersey
city: Buffalo
country: United States
facility: Galderma Investigational Site 8741
state: New York
city: Cortland
country: United States
facility: Galderma Investigational Site 8723
state: New York
city: New York
country: United States
facility: Galderma Investigational Site 8733
state: New York
city: Greensboro
country: United States
facility: Galderma Investigational Site 8823
state: North Carolina
city: Raleigh
country: United States
facility: Galderma Investigational Site 8030
state: North Carolina
city: Cincinnati
country: United States
facility: Galderma Investigational Site 8747
state: Ohio
city: Portland
country: United States
facility: Galderma Investigational Site 8212
state: Oregon
city: Pittsburgh
country: United States
facility: Galderma Investigational Site 8721
state: Pennsylvania
city: North Charleston
country: United States
facility: Galderma Investigational Site 8713
state: South Carolina
city: Chattanooga
country: United States
facility: Galderma Investigational Site 8705
state: Tennessee
city: Houston
country: United States
facility: Galderma Investigational Site 8807
state: Texas
city: Waco
country: United States
facility: Galderma Investigational Site 8618
state: Texas
city: Webster
country: United States
facility: Galderma Investigational Site 8003
state: Texas
city: Salt Lake City
country: United States
facility: Galderma Investigational Site 8672
state: Utah
city: Richmond
country: United States
facility: Galderma Investigational Site 8896
state: Virginia
city: Seattle
country: United States
facility: Galderma Investigational Site 8434
state: Washington
city: Brussel
country: Belgium
facility: Galderma Investigational Site 5448
city: Gent
country: Belgium
facility: Galderma Investigational Site 6164
city: Leuven
country: Belgium
facility: Galderma Investigational Site 6038
city: Liège
country: Belgium
facility: Galderma Investigational Site 6162
city: Pleven
country: Bulgaria
facility: Galderma Investigational Site 6029
city: Sofia
country: Bulgaria
facility: Galderma Investigational Site 6051
city: Sofia
country: Bulgaria
facility: Galderma Investigational Site 6078
city: Sofia
country: Bulgaria
facility: Galderma Investigational Site 6102
city: Sofia
country: Bulgaria
facility: Galderma Investigational Site 6165
city: Sofia
country: Bulgaria
facility: Galderma Investigational Site 6216
city: Sofia
country: Bulgaria
facility: Galderma Investigational Site 6046
city: Sofia
country: Bulgaria
facility: Galderma Investigational Site 6080
city: Sofia
country: Bulgaria
facility: Galderma Investigational Site 6079
city: Sofia
country: Bulgaria
facility: Galderma Investigational Site 6250
city: Stara Zagora
country: Bulgaria
facility: Galderma Investigational Site 6251
city: Tallinn
country: Estonia
facility: Galderma Investigational Site 6069
city: Tallin
country: Estonia
facility: Galderma Investigational Site 6068
city: Tartu
country: Estonia
facility: Galderma Investigational Site 6067
city: Le Mans
country: France
facility: Galderma Investigational Site 6198
city: Lille
country: France
facility: Galderma Investigational Site 5031
city: Martigues
country: France
facility: Galderma Investigational Site 6170
city: Nantes
country: France
facility: Galderma Investigational Site 6167
city: Nice
country: France
facility: Galderma Investigational Site 5140
city: Paris
country: France
facility: Galderma Investigational Site 6133
city: Paris
country: France
facility: Galderma Investigational Site 6166
city: Pierre-Bénite
country: France
facility: Galderma Investigational Site 5407
city: Quimper
country: France
facility: Galderma Investigational Site 6135
city: Toulon
country: France
facility: Galderma Investigational Site 6197
city: Toulouse
country: France
facility: Galderma Investigational Site 6169
city: Valence
country: France
facility: Galderma Investigational Site 6168
city: Tbilisi
country: Georgia
facility: Galderma Investigational Site 6238
city: Tbilisi
country: Georgia
facility: Galderma Investigational Site 6227
city: Tbilisi
country: Georgia
facility: Galderma Investigational Site 6230
city: Tbilisi
country: Georgia
facility: Galderma Investigation Site 6228
city: Tbilisi
country: Georgia
facility: Galderma Investigational Site 6224
city: Tbilisi
country: Georgia
facility: Galderma Investigational Site 6235
city: Tbilisi
country: Georgia
facility: Galderma Investigational Site 6234
city: Zugdidi
country: Georgia
facility: Galderma Investigational Site 6236
city: Aachen
country: Germany
facility: Galderma Investigational Site 5482
city: Augsburg
country: Germany
facility: Galderma Investigational Site 5566
city: Bonn
country: Germany
facility: Galderma Investigational Site 6082
city: Dresden
country: Germany
facility: Galderma Investigational Site 6132
city: Duesseldorf
country: Germany
facility: Galderma Investigational Site 6031
city: Frankfurt
country: Germany
facility: Galderma Investigational Site 6083
city: Gera
country: Germany
facility: Galderma Investigational Site 5442
city: Goettigen
country: Germany
facility: Galderma Investigational Site 6081
city: Halle
country: Germany
facility: Galderma Investigational Site 6062
city: Hamburg
country: Germany
facility: Galderma Investigational Site 6041
city: Hamburg
country: Germany
facility: Galderma Investigational Site 6150
city: Hamburg
country: Germany
facility: Galderma Investigational Site 6040
city: Heidelberg
country: Germany
facility: Galderma Investigational Site 5469
city: Kiel
country: Germany
facility: Galderma Investigational Site 6086
city: Mainz
country: Germany
facility: Galderma Investigational Site 6084
city: Munich
country: Germany
facility: Galderma Investigational Site 5382
city: Budapest
country: Hungary
facility: Galderma Investigational Site 6147
city: Budapest
country: Hungary
facility: Galderma Investigational Site 5513
city: Debrecen
country: Hungary
facility: Galderma Investigational Site 5567
city: Debrecen
country: Hungary
facility: Galderma Investigational Site 6026
city: Gyula
country: Hungary
facility: Galderma Investigational Site 6254
city: Veszprém
country: Hungary
facility: Galderma Investigational Site 6053
city: Bologna
country: Italy
facility: Galderma Investigational Site 6145
city: Chieti
country: Italy
facility: Galderma Investigational Site 6141
city: L'Aquila
country: Italy
facility: Galderma Investigational Site 6045
city: Parma
country: Italy
facility: Galderma Investigational Site 6151
city: Pavia
country: Italy
facility: Galderma Investigational Site 6180
city: Pisa
country: Italy
facility: Galderma Investigational Site 6143
city: Roma
country: Italy
facility: Galderma Investigational Site 6044
city: Roma
country: Italy
facility: Galderma Investigational Site 6049
city: Rome
country: Italy
facility: Galderma Investigational Site 6177
city: Rozzano
country: Italy
facility: Galderma Investigational Site 6155
city: Vicenza
country: Italy
facility: Galderma Investigational Site 6175
city: Białystok
country: Poland
facility: Galderma Investigational Site 5773
city: Chorzów
country: Poland
facility: Galderma Investigational Site 6097
city: Cracovia
country: Poland
facility: Galderma Investigational Site 5362
city: Katowice
country: Poland
facility: Galderma Investigational Site 5021
city: Kraków
country: Poland
facility: Galderma Investigational Site 6052
city: Lublin
country: Poland
facility: Galderma Investigational Site 5367
city: Nowa Sól
country: Poland
facility: Galderma Investigational Site 5377
city: Olsztyn
country: Poland
facility: Galderma Investigational Site 6063
city: Poznań
country: Poland
facility: Galderma Investigational Site 6085
city: Rzeszów
country: Poland
facility: Galderma Investigational Site 5495
city: Szczecin
country: Poland
facility: Galderma Investigational Site 6130
city: Tarnów
country: Poland
facility: Galderma Investigational Site 6048
city: Warsaw
country: Poland
facility: Galderma Investigational Site 6126
city: Warsaw
country: Poland
facility: Galderma Investigational Site 5707
city: Wrocław
country: Poland
facility: Galderma Investigational Site 6185
city: Wrocław
country: Poland
facility: Galderma Investigational Site 6096
city: Łódź
country: Poland
facility: Galderma Investigational Site 5363
city: Singapore
country: Singapore
facility: Galderma Investigational Site 6124
city: Singapore
country: Singapore
facility: Galderma Investigational Site 6077
city: Singapore
country: Singapore
facility: Galderma Investigational Site 5499
Study officials:
References: