Dose-ranging Study of Nemolizumab in Atopic Dermatitis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Nemolizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Nemolizumab (low dose) | Drug: Nemolizumab<br>* Injection every 4 weeks during 24 weeks (last injection at week 20)<br>|
| Experimental: Group 2<br>Nemolizumab (medium dose) | Drug: Nemolizumab<br>* Injection every 4 weeks during 24 weeks (last injection at week 20)<br>|
| Experimental: Group 3<br>Nemolizumab (high dose) | Drug: Nemolizumab<br>* Injection every 4 weeks during 24 weeks (last injection at week 20)<br>|
| Placebo Comparator: Group 4<br>Nemolizumab placebo | Drug: Placebo<br>* Injection every 4 weeks during 24 weeks (last injection at week 20)<br>|

What is the study measuring?
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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 |