Dose-ranging Study of Nemolizumab in Atopic Dermatitis

Atopic Dermatitis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03100344
• Other study ID #: RD.03.SPR.114322
• Status: Completed
• Phase: Phase 2
• Start date: June 14, 2017
• Est. completion date: September 21, 2018

Study information

• Verified date: October 2019
• Source: Galderma R&D
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 226
• Est. completion date: September 21, 2018
• Est. primary completion date: July 19, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Nemolizumab
Injection every 4 weeks during 24 weeks (last injection at week 20)
• Placebo
Injection every 4 weeks during 24 weeks (last injection at week 20)

Locations

Country	Name	City	State
Australia	Galderma Investigational Site	Benowa
Australia	Galderma Investigational Site	Kogarah
Australia	Galderma Investigational Site	Melbourne
Australia	Galderma Investigational Site	Phillip
Canada	Galderma Investigational Site	Calgary
Canada	Galderma Investigational Site	Markham
Canada	Galderma Investigational Site	Oakville
Canada	Galderma Investigational Site	Ottawa
Canada	Galderma Investigational Site	Ottawa
Canada	Galderma Investigational Site	Peterborough
Canada	Galderma Investigational Site	Richmond Hill
Canada	Galderma Investigational Site	Sainte-Foy
Canada	Galderma Investigational Site	Waterloo
France	Galderma Investigational Site	Bordeaux
France	Galderma Investigational Site	Lille
France	Galderma Investigational Site	Marseille
France	Galderma Investigational Site	Nice
France	Galderma Investigational Site	Paris
France	Galderma Investigational Site	Toulouse
Germany	Galderma Investigational Site	Berlin
Germany	Galderma Investigational Site	Berlin
Germany	Galderma Investigational Site	Darmstadt
Germany	Galderma Investigational Site	Erlangen
Germany	Galderma Investigational Site	Frankfurt
Germany	Galderma Investigational Site	Hamburg
Germany	Galderma Investigational Site	Hannöver
Germany	Galderma Investigational Site	Heidelberg
Germany	Galderma Investigational Site	Langenau
Germany	Galderma Investigational Site	Mainz
Germany	Galderma Investigational Site	München
Germany	Galderma Investigational Site	Osnabrück
Germany	Galderma Investigational Site	Stuttgart
Poland	Galderma Investigational Site	Katowice
Poland	Galderma Investigational Site	Katowice
Poland	Galderma Investigational Site	Kraków
Poland	Galderma Investigational Site	Lódz
Poland	Galderma Investigational Site	Lublin
Poland	Galderma Investigational Site	Warsaw
Poland	Galderma Investigational Site	Warsaw
Poland	Galderma Investigational Site	Warsaw
Poland	Galderma Investigational Site	Wroclaw
United States	Galderma Investigational site	Beverly Hills	California
United States	Galderma Investigational site	Birmingham	Alabama
United States	Galderma Investigational site	Chapel Hill	North Carolina
United States	Galderma Investigational site	Columbus	Georgia
United States	Galderma Investigational site	Dallas	Texas
United States	Galderma Investigational Site	Darien	Illinois
United States	Galderma Investigational Site	Farmington Hills	Michigan
United States	Galderma Investigational site	Forest Hills	New York
United States	Galderma Investigational site	Fort Smith	Arkansas
United States	Galderma Investigational site	Fountain Valley	California
United States	Galderma Investigational site	Fremont	California
United States	Galderma Investigational Site	Johnston	Rhode Island
United States	Galderma Investigational site	Miami	Florida
United States	Galderma Investigational site	New Orleans	Louisiana
United States	Galderma Investigational site	New York	New York
United States	Galderma Investigational Site	New York	New York
United States	Galderma Investigational Site	Overland Park	Kansas
United States	Galderma Investigational site	Richmond	Virginia
United States	Galderma Investigational site	Rolling Hills Estates	California
United States	Galderma Investigational site	San Antonio	Texas
United States	Galderma Investigational site	Sandy Springs	Georgia
United States	Galderma Investigational site	Santa Ana	California
United States	Galderma Investigational site	Santa Monica	California
United States	Galderma Investigational site	Tampa	Florida
United States	Galderma Investigational Site	Tampa	Florida
United States	Galderma Investigational Site	Waco	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Galderma R&D

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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