Safety and Efficacy of Nemolizumab in PN

Study Overview
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Brief Summary
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The aim of this study is to assess the safety and efficacy of nemolizumab in subjects with prurigo nodularis.

Detailed Description
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This is a randomized, placebo-controlled, double-blinded, parallel group, multicenter study to evaluate the safety and efficacy of nemolizumab over a 12-week treatment period in patients suffering from prurigo nodularis compared to its placebo.

Official Title
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A Study to Assess the Safety and Efficacy of Nemolizumab (CD14152) in Subjects With Prurigo Nodularis (PN)

Conditions
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Prurigo Nodularis

Intervention / Treatment
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* Drug: CD14152 Dose A
* Drug: CD14152 placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female of at least 18 years at screening Clinical diagnosis of PN for at least 6 months with: Prurigo lesions on upper limbs with or without lesions on the trunk or lower limbs At least 20 nodules on the entire body with a bilateral distribution Severe pruritus defined as follows on a Numerical Rating Scale (NRS) At the Screening visit 1: Mean of the worst daily intensity of the NRS score is ≥ 7 over the previous 3 days At the Baseline visit: Mean of the worst daily intensity of the NRS score is ≥ 7 over the previous week; NOTE: NRS score should be measured on at least 5 days during the week preceding the baseline visit. Female subjects must fulfill one of the criteria below: Female subjects of non-childbearing potential (postmenopausal [absence of menstrual bleeding for 1 year prior to screening, without any other medical reason], hysterectomy or bilateral oophorectomy); Female subjects of childbearing potential who agree to a true abstinence (when in line with the preferred and usual lifestyle of the subject), or to use an effective method of contraception throughout the clinical trial and for 120 days after the last study drug administration: Exclusion Criteria: Chronic pruritus resulting from another condition than PN such as scabies, insect bite, lichen simplex chronicus, psoriasis, acne, folliculitis, habitual picking, lymphomatoid papulosis, chronic actinic dermatitis, dermatitis herpetiformis, sporotrichosis, bullous disease Unilateral lesions of prurigo (e.g only one arm affected) Cutaneous bacterial or viral infection within 1 week before the baseline visit. Infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics or antifungals within 1 week before the screening visit, or during the screening period, unless completely resolved at the screening/ baseline visits respectively, Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with the interpretation of the clinical trial results and/or put the subject at Chronic pruritus resulting from another condition than PN such as scabies, insect bite, lichen simplex chronicus, psoriasis, acne, folliculitis, habitual picking, lymphomatoid papulosis, chronic actinic dermatitis, dermatitis herpetiformis, sporotrichosis, bullous disease

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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received 3 subcutaneous injections of placebo (matched to nemolizumab) every 4 weeks (Q4W) up to Week 8. | Drug: CD14152 placebo<br>* 3 subcutaneous injections (every 4 weeks during the 12-week treatment period)<br>* Other names: Placebo;|
| Experimental: Nemolizumab 0.5 mg/kg<br>Participants received 3 subcutaneous injections of nemolizumab 0.5 milligram per kilogram (mg/kg) Q4W up to Week 8. | Drug: CD14152 Dose A<br>* 3 subcutaneous injections (every 4 weeks during the 12-week treatment period)<br>* Other names: Nemolizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Weekly Average of the Peak Pruritus Numeric Rating Scale (NRS) Score at Week 4 Using Last Observation Carried Forward (LOCF) Approach | Pruritus NRS is a scale used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. Participants completed the assessment once daily at home in the evening. Participants were asked the following questions in their local language: 1) For average itch intensity: on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable', how would you rate your itch overall during the previous 24 hours?; 2) For maximum itch intensity: on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?. Where, higher score indicated worst imaginable itch. Missing values including those who took rescue medication were replaced by LOCF approach. | Baseline, Week 4 | 
| Percent Change From Baseline in Weekly Average of the Peak Pruritus Numeric Rating Scale Score at Week 4 Using Multiple Imputation (MI) Method | Pruritus NRS is a scale used by the participants to report the intensity of their pruritus (itch) during the last 24. Participants completed the assessment once daily at home in the evening. Participants were asked the following questions in their local language: 1) For average itch intensity: on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable', how would you rate your itch overall during the previous 24 hours?; 2) For maximum itch intensity: on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?. Where, higher score indicated worst imaginable itch. Multiple imputation generated twenty-five sets of data with missing values imputed from observed data using linear regression. | Baseline, Week 4 | 
| Percent Change From Baseline in Weekly Average of the Peak Pruritus Numeric Rating Scale Score at Week 4 Using Observed Data | Pruritus NRS is a scale used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. Participants completed the assessment once daily at home in the evening. Participants were asked the following questions in their local language: 1) For average itch intensity: on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable', how would you rate your itch overall during the previous 24 hours?; 2) For maximum itch intensity: on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?. Where, higher score indicated worst imaginable itch. | Baseline, Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Weekly Average of the Peak Pruritus Numeric Rating Scale Score at Each Visit Using LOCF Approach | Pruritus NRS is a scale used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. Participants completed the assessment once daily at home in the evening. Participants were asked the following questions in their local language: 1) For average itch intensity: on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable', how would you rate your itch overall during the previous 24 hours?; 2) For maximum itch intensity: on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?. Where, higher score indicated worst imaginable itch. Missing values including those who took rescue medication were replaced by LOCF approach. | Baseline, Weeks 1, 2, 4, 8, 12, 16 and 18 | 
| Absolute Change From Baseline in Weekly Average of the Peak Pruritus Numeric Rating Scale Score at Each Visit Using LOCF Approach | Pruritus NRS is a scale used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. Participants completed the assessment once daily at home in the evening. Participants were asked the following questions in their local language: 1) For average itch intensity: on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable', how would you rate your itch overall during the previous 24 hours?; 2) For maximum itch intensity: on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?. Where, higher score indicated worst imaginable itch. Missing values including those who took rescue medication were replaced by LOCF approach. | Baseline, Weeks 1, 2, 4, 8, 12, 16 and 18 | 
| Percent Change From Baseline in Weekly Average of the Average Pruritus Numeric Rating Scale Score at Each Visit Using LOCF Approach | Pruritus NRS is a scale used by the participants to report the intensity of their pruritus (itch) during the last 24. Participants completed the assessment once daily at home in the evening. Participants were asked the following questions in their local language: 1) For average itch intensity: on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable', how would you rate your itch overall during the previous 24 hours?; 2) For maximum itch intensity: on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?. Where, higher score indicated worst imaginable itch. Missing values including those who took rescue medication were replaced by LOCF approach. | Baseline, Weeks 1, 2, 4, 8, 12, 16 and 18 | 
| Absolute Change From Baseline in Weekly Average of the Average Pruritus Numeric Rating Scale Score at Each Visit Using LOCF Approach | Pruritus NRS is a scale used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. Participants completed the assessment once daily at home in the evening. Participants were asked the following questions in their local language: 1) For average itch intensity: on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable', how would you rate your itch overall during the previous 24 hours?; 2) For maximum itch intensity: on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?. Where, higher score indicated worst imaginable itch. Missing values including those who took rescue medication were replaced by LOCF approach. | Baseline, Weeks 1, 2, 4, 8, 12, 16 and 18 | 
| Percent Change From Baseline in Weekly Average of the Peak of Pruritus Verbal Rating Scale (VRS) Score at Each Visit Using LOCF Approach | VRS consists of a list of adjectives describing different levels of symptom intensity used by participants to report intensity of their pruritus (itch) over last 24 hours. Participants marked on a 5-point VRS (0=no itch, 1=mild itch, 2=moderate itch, 3=severe itch, 4=very severe itch), a response that best described their pruritus intensity in last 24 hours. Participants were asked following questions in their local language: 1) For average itch intensity: on a scale of 0-4, with 0 being 'no itch' and 4 being 'very severe itch', how would you rate your itch overall during previous 24 hours?; 2) For maximum itch intensity: on a scale of 0-4, with 0 being 'no itch' and 4 being 'very severe itch', how would you rate your worst itch during previous 24 hours?. Where, higher score indicated very severe itch. Missing values including those who took rescue medication were replaced by LOCF approach. | Baseline, Weeks 1, 2, 4, 8, 12, 16 and 18 | 
| Absolute Change From Baseline in Weekly Average of the Peak of Pruritus Verbal Rating Scale Score at Each Visit Using LOCF Approach | VRS consists of a list of adjectives describing different levels of symptom intensity used by participants to report intensity of their pruritus (itch) over last 24 hours. Participants marked on a 5-point VRS (0=no itch, 1=mild itch, 2=moderate itch, 3=severe itch, 4=very severe itch), a response that best described their pruritus intensity in last 24 hours. Participants were asked following questions in their local language: 1) For average itch intensity: on a scale of 0-4, with 0 being 'no itch' and 4 being 'very severe itch', how would you rate your itch overall during previous 24 hours?; 2) For maximum itch intensity: on a scale of 0-4, with 0 being 'no itch' and 4 being 'very severe itch', how would you rate your worst itch during previous 24 hours?. Where, higher score indicated very severe itch. Missing values including those who took rescue medication were replaced by LOCF approach. | Baseline, Weeks 1, 2, 4, 8, 12,16 and 18 | 
| Percent Change From Baseline in Weekly Average of the Average Pruritus Verbal Rating Scale Score at Each Visit Using LOCF Approach | VRS consists of a list of adjectives describing different levels of symptom intensity used by participants to report intensity of their pruritus (itch) over last 24 hours. Participants marked on a 5-point VRS (0=no itch, 1=mild itch, 2=moderate itch, 3=severe itch, 4=very severe itch), a response that best described their pruritus intensity in last 24 hours. Participants were asked following questions in their local language: 1) For average itch intensity: on a scale of 0-4, with 0 being 'no itch' and 4 being 'very severe itch', how would you rate your itch overall during previous 24 hours?; 2) For maximum itch intensity: on a scale of 0-4, with 0 being 'no itch' and 4 being 'very severe itch', how would you rate your worst itch during previous 24 hours?. Where, higher score indicated very severe itch. Missing values including those who took rescue medication were replaced by LOCF approach. | Baseline, Weeks 1, 2, 4, 8, 12, 16 and 18 | 
| Absolute Change From Baseline in Weekly Average of the Average Verbal Rating Scale Score at Each Visit Using LOCF Approach | VRS consists of a list of adjectives describing different levels of symptom intensity used by participants to report intensity of their pruritus (itch) over last 24 hours. Participants marked on a 5-point VRS (0=no itch, 1=mild itch, 2=moderate itch, 3=severe itch, 4=very severe itch), a response that best described their pruritus intensity in last 24 hours. Participants were asked following questions in their local language: 1) For average itch intensity: on a scale of 0-4, with 0 being 'no itch' and 4 being 'very severe itch', how would you rate your itch overall during previous 24 hours?; 2) For maximum itch intensity: on a scale of 0-4, with 0 being 'no itch' and 4 being 'very severe itch', how would you rate your worst itch during previous 24 hours?. Where, higher score indicated very severe itch. Missing values including those who took rescue medication were replaced by LOCF approach. | Baseline, Weeks 1, 2, 4, 8, 12,16 and 18 | 
| Dynamic Pruritus Score (DPS) at 24, 48, and 72 Hours After First Injection and Before Second Injection (Week 4) | The 9-point DPS is a dynamic scale used by participants to evaluate the change of their pruritus compared with an earlier time point. The scale ranges from 0 (strongly worsened pruritus) to 8 ([almost] no pruritus anymore), including intermediate marks for slightly improved/worsened, moderately improved/worsened, and rather improved/worsened. Participants recorded their DPS score in their local language, and completed the assessment 24, 48 and 72 hours after the first injection at baseline and at week 4 before the second injection. | After 24, 48, 72 hours of first Injection and before second injection (Week 4) | 
| Prurigo Activity Score (PAS) Item 5: Overall Number of Prurigo Lesions at Week 12 | PAS includes 7-descriptive items; 1) lesions type (papules nodules/plaques/umbilicated ulcers/ulcers/hypo-/hyperpigmented maculae); 2) number (prurigo lesions on whole body); 3) distribution (disseminated/localized [only 1/2 areas affected]/neither of them); 4) affected areas (forearm/upper arm/lower and upper leg/trunk/head); 5) number of prurigo lesions in selected area; 6) activity (prurigo lesions with excoriations/crusts and healed prurigo lesions compared to all prurigo lesions) and 7) front and back, areas of marked monitor lesions to recognize on next visit. | Baseline, Week 12 | 
| Prurigo Activity Score (PAS) Item 6: Number of Participants With Defined Stages of Excoriation/Crusts and Healed Lesions at Each Visit | PAS includes 7-descriptive items; 1) lesions type (papules nodules/plaques/umbilicated ulcers/ulcers/hypo-/hyperpigmented maculae); 2) number (prurigo lesions on whole body); 3) distribution (disseminated/localized [only 1/2 areas affected]/neither of them); 4) affected areas (forearm/upper arm/lower and upper leg/trunk/head); 5) number of prurigo lesions in selected area; 6) activity (prurigo lesions with excoriations/crusts and healed prurigo lesions compared to all prurigo lesions) and 7) front and back, areas of marked monitor lesions to recognize on next visit. Item 6 has 5 stages (0-4) where each stage represents percentage of prurigo lesions with excoriations/crusts and healed prurigo lesions compared to all prurigo lesions: excoriations/crusts lesions; stage 0=0%, 1=1-25%, 2=26-50%, 3=51-75%, 4=76-100%; for healed lesions; stage 0=100%, 1=75-99%, 2=50-74%, 3=25-49%, 4=0-24%. | Day 1 (Baseline), Weeks 4, 8, 12 and 18 | 
| Investigator Global Assessment (IGA) Score at Each Visit | IGA is a 5-point scale used by the investigator or trained designee to evaluate the severity of the disease ranging from 0 to 4 where, 0 = clear, 1= almost clear, 2 = mild, 3 = moderate and 4 severe. IGA corresponds to the overall assessment of the severity of prurigo including presence of crust and nodules or skin bleeding. Higher score indicated greater severity of disease. | Day 1 (Baseline), Weeks 4, 8, 12 and 18 | 
| Percentage of Participants Achieving Investigator Global Assessment Success (Defined as IGA= 0 [Clear] or IGA = 1 [Almost Clear] With Two-point Improvement From Baseline) at Week 12 | IGA is a 5-point scale used by the investigator or trained designee to evaluate the severity of the disease ranging from 0 to 4 where, 0 = clear, 1= almost clear, 2 = mild, 3 = moderate and 4 severe. IGA corresponds to the overall assessment of the severity of prurigo including presence of crust and nodules or skin bleeding. Higher score indicated greater severity of disease. | Week 12 |