Dose-ranging Study of Nemolizumab in Atopic Dermatitis

Randomized, Double-blind, Multi-center, Parallel-group, Placebo-controlled Dose-ranging Study to Assess the Efficacy and Safety of Nemolizumab in Moderate-to-severe Atopic Dermatitis Subjects With Severe Pruritus Receiving Topical Corticosteroids (TCS)

Assess the efficacy of several subcutaneous doses of nemolizumab in moderate-to-severe atopic dermatitis (AD) subjects with severe pruritus receiving TCS, who were not adequately controlled with topical treatments.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Nemolizumab; Drug: Placebo

Detailed Description

The aim of the study is to assess the efficacy of several subcutaneous doses of nemolizumab in moderate-to-severe atopic dermatitis (AD) subjects with severe pruritus receiving topical corticosteroids, who were not adequately controlled with topical treatments.

• Study Type: Interventional
• Enrollment (Actual): 226
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Benowa, Australia, 4217 QLD
    • Galderma Investigational Site
  • Kogarah, Australia, NSW 2217
    • Galderma Investigational Site
  • Melbourne, Australia, VIC3002
    • Galderma Investigational Site
  • Phillip, Australia, ACT2606
    • Galderma Investigational Site
• Canada
  • Calgary, Canada, AB T3A 2N1
    • Galderma Investigational Site
  • Markham, Canada, ON L3P 1X2
    • Galderma Investigational Site
  • Oakville, Canada, ON L6J 7W5
    • Galderma Investigational Site
  • Ottawa, Canada, K1G 6C6
    • Galderma Investigational Site
  • Ottawa, Canada, ON K2G 6E2
    • Galderma Investigational Site
  • Peterborough, Canada, K9J
    • Galderma Investigational Site
  • Richmond Hill, Canada, ON L4C
    • Galderma Investigational Site
  • Sainte-Foy, Canada, QC G1V4X7
    • Galderma Investigational Site
  • Waterloo, Canada, ON N2J 1C4
    • Galderma Investigational Site
• France
  • Bordeaux, France, 33075
    • Galderma Investigational Site
  • Lille, France, 59037
    • Galderma Investigational Site
  • Marseille, France, 13385
    • Galderma Investigational Site
  • Nice, France, 06202
    • Galderma Investigational Site
  • Paris, France, 75010
    • Galderma Investigational Site
  • Toulouse, France, 31059
    • Galderma Investigational Site
• Germany
  • Berlin, Germany, 10117
    • Galderma Investigational Site
  • Berlin, Germany, 10789
    • Galderma Investigational Site
  • Darmstadt, Germany, 64283
    • Galderma Investigational Site
  • Erlangen, Germany, 91054
    • Galderma Investigational Site
  • Frankfurt, Germany, 60590
    • Galderma Investigational Site
  • Hamburg, Germany, 20354
    • Galderma Investigational Site
  • Hannöver, Germany, 30625
    • Galderma Investigational Site
  • Heidelberg, Germany, 69120
    • Galderma Investigational Site
  • Langenau, Germany, 89129
    • Galderma Investigational Site
  • Mainz, Germany, 55131
    • Galderma Investigational Site
  • München, Germany, 80337
    • Galderma Investigational Site
  • Osnabrück, Germany, 49074
    • Galderma Investigational Site
  • Stuttgart, Germany, 70718
    • Galderma Investigational Site
• Poland
  • Katowice, Poland, 40-123
    • Galderma Investigational Site
  • Katowice, Poland, 40-648
    • Galderma Investigational Site
  • Kraków, Poland, 31-024
    • Galderma Investigational Site
  • Lublin, Poland, 20-080
    • Galderma Investigational Site
  • Warsaw, Poland, 01-817
    • Galderma Investigational Site
  • Warsaw, Poland, 02-758
    • Galderma Investigational Site
  • Warsaw, Poland, 02-625
    • Galderma Investigational Site
  • Wrocław, Poland, 51-318
    • Galderma Investigational Site
  • Łódź, Poland, 90-436
    • Galderma Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Galderma Investigational Site
  • Arkansas
    • Fort Smith, Arkansas, United States, 72916
      • Galderma Investigational Site
  • California
    • Beverly Hills, California, United States, 90212
      • Galderma Investigational Site
    • Fountain Valley, California, United States, 92708
      • Galderma Investigational Site
    • Fremont, California, United States, 94538
      • Galderma Investigational Site
    • Rolling Hills Estates, California, United States, 90274
      • Galderma Investigational Site
    • Santa Ana, California, United States, 92701
      • Galderma Investigational Site
    • Santa Monica, California, United States, 90404
      • Galderma Investigational Site
  • Florida
    • Miami, Florida, United States, 33135
      • Galderma Investigational Site
    • Tampa, Florida, United States, 33607
      • Galderma Investigational Site
    • Tampa, Florida, United States, 33624
      • Galderma Investigational Site
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Galderma Investigational Site
    • Sandy Springs, Georgia, United States, 30328
      • Galderma Investigational Site
  • Illinois
    • Darien, Illinois, United States, 60561
      • Galderma Investigational Site
  • Kansas
    • Overland Park, Kansas, United States, 66215
      • Galderma Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Galderma Investigational Site
  • Michigan
    • Farmington Hills, Michigan, United States, 78334
      • Galderma Investigational Site
  • New York
    • Forest Hills, New York, United States, 11375
      • Galderma Investigational Site
    • New York, New York, United States, 10075
      • Galderma Investigational Site
    • New York, New York, United States, 10025
      • Galderma Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27516
      • Galderma Investigational Site
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Galderma Investigational Site
  • Texas
    • Dallas, Texas, United States, 75230
      • Galderma Investigational Site
    • San Antonio, Texas, United States, 78218
      • Galderma Investigational Site
    • Waco, Texas, United States, 76710
      • Galderma Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23220
      • Galderma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects ≥ 18 years (or legal age when higher)
• Chronic AD, that has been present for at least 2 years before the visit
• Eczema Area and Severity Index (EASI) score ≥12
• Investigator Global Assessment (IGA) score ≥ 3
• AD involvement ≥ 10% of Body Surface Area (BSA)
• Severe pruritus on at least 3 of the last 7 days before the visit
• Documented recent history (within 6 months before the visit) of inadequate response to topical medications

• Female subjects must fulfill one of the criteria below:

  • Female subjects of non-childbearing potential
  • Female subjects of childbearing potential who agree to a true abstinence or to use an effective or highly effective method of contraception throughout the clinical trial and for 120 days after the last study drug administration

Exclusion Criteria:

• Body weight < 45 kg
• subjects with a medical history of asthma requiring hospitalization in the last 12 months before screening visit and/or whose asthma has not been well-controlled during the last 3 months before the screening visit and/or Peak Expiratory Flow (PEF) <80% of the predicted value
• Cutaneous bacterial or viral infection within 1 week before the screening visit or during the run-in period
• Infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics or antifungals within 1 week before the screening visit or during the run-in period
• History of intolerance to low or mid potency TCS or for whom TCS is not advisable

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group 1; Nemolizumab (low dose)	Drug: Nemolizumab; Injection every 4 weeks during 24 weeks (last injection at week 20)
EXPERIMENTAL: Group 2; Nemolizumab (medium dose)	Drug: Nemolizumab; Injection every 4 weeks during 24 weeks (last injection at week 20)
EXPERIMENTAL: Group 3; Nemolizumab (high dose)	Drug: Nemolizumab; Injection every 4 weeks during 24 weeks (last injection at week 20)
PLACEBO_COMPARATOR: Group 4; Nemolizumab placebo	Drug: Placebo; Injection every 4 weeks during 24 weeks (last injection at week 20)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Eczema Area and Severity Index (EASI) at Week 24	EASI is a composite score ranging from 0 to 72.The severity of erythema, induration/papulation, excoriation, and lichenification was assessed on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. Higher scores indicate worse outcome.	From Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Achieving Pruritus Categorical Scale (PCS) Success (Defined as a Weekly Prorated Rounded Average PCS ≤1 [None - Mild]) at Week 24	The 4-point pruritus categorical scale was provided in their local language for the participants to report the intensity of their pruritus. Overall itching was scored as 0 for absence of pruritus and 3 for severe pruritus (bothersome itching/scratching that disturbs sleep). Higher scores indicate worse outcome.	Week 24
Number of Participants With an Improvement of Weekly Average Peak Pruritus Numeric Rating Scale (NRS) ≥4 at Each Timepoint up to Week 24	Pruritus NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores were provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome.	From Week 1 to Week 24
Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) at Week 24	SCORAD ranges from 0 to 103 and has three components: extent (body surface area [BSA]), signs, and symptoms of AD. The severity of the 6 signs of AD (erythema/darkening, edema/papulation, oozing/crusting, excoriation, lichenification/prurigo and dryness), was assessed, each on a scale ranging from 0 (none) to 3 (severe).The component of extent corresponded to the extent of BSA affected by atopic dermatitis.The BSA involvement of AD was assessed for each part of the body (the possible highest score for each region is: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]), and was reported as a percentage of all major body sections combined. Participants were also asked to evaluate their symptoms of pruritus and sleep loss (average for the last 3 days/nights), each evaluated on a Visual analog scale (VAS) from 0 to 10. Higher scores indicate worse outcome.	Baseline, Week 24
Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD) at Week 24	SCORAD ranges from 0 to 103 and has three components: extent (body surface area [BSA]), signs, and symptoms of AD. The severity of the 6 signs of AD (erythema/darkening, edema/papulation, oozing/crusting, excoriation, lichenification/prurigo and dryness), was assessed, each on a scale ranging from 0 (none) to 3 (severe).The component of extent corresponded to the extent of BSA affected by atopic dermatitis.The BSA involvement of AD was assessed for each part of the body (the possible highest score for each region is: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]), and was reported as a percentage of all major body sections combined. Participants were also asked to evaluate their symptoms of pruritus and sleep loss (average for the last 3 days/nights), each evaluated on a Visual analog scale (VAS) from 0 to 10. Higher scores indicate worse outcome.	Baseline, Week 24
Percent Change From Baseline in Weekly Average Sleep Disturbance Numeric Rating Scale (NRS) at Week 24	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 questions 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'. Higher scores indicate worse outcome.	Baseline, Week 24
Absolute Change From Baseline in Weekly Average Sleep Disturbance Numeric Rating Scale (NRS) at Week 24	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 questions 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'. Higher scores indicate worse outcome.	Baseline, Week 24
Number of Participants Achieving Investigator's Global Assessment (IGA) Success (Defined as IGA 0 [Clear] or 1 [Almost Clear]) at Each Timepoint up to Week 24	IGA is a 5-point scale ranging from 0 (clear) to 4 (severe) used to evaluate the global severity of AD. Higher scores indicate worse outcome.	From Week 1 to Week 24
Number of Participants With Eczema Area and Severity Index (EASI)-50 (Defined as Achieving 50% Reduction From Baseline in EASI Score) at Each Visit up to Week 24	EASI is a composite score ranging from 0 to 72. The severity of erythema, induration/papulation, excoriation, and lichenification were assessed on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. Higher scores indicate worse outcome.	From Week 1 to Week 24
Number of Participants With Eczema Area and Severity Index (EASI)-75 (Defined as Achieving 75% Reduction From Baseline in EASI Score) at Each Visit up to Week 24	EASI is a composite score ranging from 0 to 72.The severity of erythema, induration/papulation, excoriation, and lichenification were assessed on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. Higher scores indicate worse outcome.	From Week 1 to Week 24
Number of Participants With Eczema Area and Severity Index (EASI)-90 (Defined as Achieving 90% Reduction From Baseline in EASI Score) at Each Visit up to Week 24	EASI is a composite score ranging from 0 to 72.The severity of erythema, induration/papulation, excoriation, and lichenification were assessed on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. Higher scores indicate worse outcome.	From Week 1 to Week 24
Number of Participants Achieving Investigator Global Assessment (IGA) Success (Defined as IGA 0 [Clear] or 1 [Almost Clear]) and a Reduction of ≥2 Points at Each Visit up to Week 24	IGA is a 5-point scale ranging from 0 (clear) to 4 (severe) used to evaluate the global severity of AD. Higher scores indicate worse outcome.	Week 1 to Week 24
Percentage Change From Baseline in Eczema Area and Severity Index (EASI) at Each Visit up to Week 24	EASI is a composite score ranging from 0 to 72.The severity of erythema, induration/papulation, excoriation, and lichenification was assessed on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. Higher scores indicate worse outcome.	From Baseline to Week 24
Percentage Change From Baseline in Weekly Average of the Peak Pruritus Numeric Rating Scale (NRS) at Each Visit up to Week 24	Pruritus NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores were provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome.	At baseline and Week 24
Number of Participants With Adverse Events	To evaluate the safety of nemolizumab in participants with moderate-to-severe AD	From screening to Follow-up visit (Week 32)/Early termination visit
Absolute Change From Baseline in Weekly Average of the Peak Pruritus Numeric Rating Scale (NRS) at Each Visit up to Week 24	Pruritus NRS is a scale to be used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores were provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome.	Baseline to Week 24
Absolute Change From Baseline in Weekly Average of the Average Pruritus Numeric Rating Scale (NRS) at Each Visit up to Week 24	Pruritus NRS is a scale to be used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For average itch intensity: the scores were provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome.	Baseline to Week 24
Percentage Change From Baseline in Weekly Average of the Average Pruritus Numeric Rating Scale (NRS) at Each Visit up to Week 24	Pruritus NRS is a scale to be used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For average itch intensity: the scores were provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome.	Baseline to Week 24

Collaborators and Investigators

• Sponsor: Galderma R&D

Publications and helpful links

General Publications

• Silverberg JI, Pinter A, Pulka G, Poulin Y, Bouaziz JD, Wollenberg A, Murrell DF, Alexis A, Lindsey L, Ahmad F, Piketty C, Clucas A. Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus. J Allergy Clin Immunol. 2020 Jan;145(1):173-182. doi: 10.1016/j.jaci.2019.08.013. Epub 2019 Aug 23.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 14, 2017
• Primary Completion (ACTUAL): July 19, 2018
• Study Completion (ACTUAL): September 21, 2018

Study Registration Dates

• First Submitted: March 29, 2017
• First Submitted That Met QC Criteria: March 29, 2017
• First Posted (ACTUAL): April 4, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 22, 2019
• Last Update Submitted That Met QC Criteria: October 3, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: RD.03.SPR.114322

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No