Safety and Efficacy of Nemolizumab in PN

Phase 2

Completed

Conditions: Prurigo Nodularis

Interventions: Drug: CD14152 placebo
Drug: CD14152 Dose A

Registration Number: NCT03181503

Lead Sponsor: Galderma R&D

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

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 70

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	CD14152 placebo	Participants received 3 subcutaneous injections of placebo (matched to nemolizumab) every 4 weeks (Q4W) up to Week 8.
Nemolizumab 0.5 mg/kg	CD14152 Dose A	Participants received 3 subcutaneous injections of nemolizumab 0.5 milligram per kilogram (mg/kg) Q4W up to Week 8.

Primary Outcome Measures

Name	Time	Method
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	Baseline, Week 4	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.
Percent Change From Baseline in Weekly Average of the Peak Pruritus Numeric Rating Scale Score at Week 4 Using Observed Data	Baseline, Week 4	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.
Percent Change From Baseline in Weekly Average of the Peak Pruritus Numeric Rating Scale Score at Week 4 Using Multiple Imputation (MI) Method	Baseline, Week 4	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.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Weekly Average of the Average Pruritus Numeric Rating Scale Score at Each Visit Using LOCF Approach	Baseline, Weeks 1, 2, 4, 8, 12, 16 and 18	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.
Absolute Change From Baseline in Weekly Average of the Peak of Pruritus Verbal Rating Scale Score at Each Visit Using LOCF Approach	Baseline, Weeks 1, 2, 4, 8, 12,16 and 18	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.
Absolute Change From Baseline in Weekly Average of the Average Pruritus Numeric Rating Scale Score at Each Visit Using LOCF Approach	Baseline, Weeks 1, 2, 4, 8, 12, 16 and 18	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.
Absolute Change From Baseline in Weekly Average of the Peak Pruritus Numeric Rating Scale Score at Each Visit Using LOCF Approach	Baseline, Weeks 1, 2, 4, 8, 12, 16 and 18	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.
Percent Change From Baseline in Weekly Average of the Peak Pruritus Numeric Rating Scale Score at Each Visit Using LOCF Approach	Baseline, Weeks 1, 2, 4, 8, 12, 16 and 18	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.
Dynamic Pruritus Score (DPS) at 24, 48, and 72 Hours After First Injection and Before Second Injection (Week 4)	After 24, 48, 72 hours of 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.
Percent Change From Baseline in Weekly Average of the Peak of Pruritus Verbal Rating Scale (VRS) Score at Each Visit Using LOCF Approach	Baseline, Weeks 1, 2, 4, 8, 12, 16 and 18	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.
Prurigo Activity Score (PAS) Item 5: Overall Number of Prurigo Lesions at Week 12	Baseline, 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.
Percent Change From Baseline in Weekly Average of the Average Pruritus Verbal Rating Scale Score at Each Visit Using LOCF Approach	Baseline, Weeks 1, 2, 4, 8, 12, 16 and 18	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.
Absolute Change From Baseline in Weekly Average of the Average Verbal Rating Scale Score at Each Visit Using LOCF Approach	Baseline, Weeks 1, 2, 4, 8, 12,16 and 18	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.
Investigator Global Assessment (IGA) Score at Each Visit	Day 1 (Baseline), Weeks 4, 8, 12 and 18	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.
Prurigo Activity Score (PAS) Item 6: Number of Participants With Defined Stages of Excoriation/Crusts and Healed Lesions at Each Visit	Day 1 (Baseline), Weeks 4, 8, 12 and 18	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%.
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	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.

Trial Locations

Locations (16): Unikl. Schleswig-Holstein - Lübeck
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Lubeck, Germany
Dermoklinika Centrum Medyczne s.c. M.Kierstan, J.Narbutt, A.Lesiak
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Łódź, Poland
Kliniczny Szpital Wojew. nr 1 im. F.Chopina w Rzeszowie
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Rzeszów, Poland
LKH-Univ. Klinikum Graz
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Graz, Austria
Centre-Hospitalier Universitaire (CHU) - Hopital Morvan - Br
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Brest, France
Charite - Campus Charite Mitte (CCM) - Dermatologie & Allergologie - Dermatologie & Allergologie
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Berlin, Germany
CHU de Nice - Hôpital Archet 2
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Nice, France
Centre Hospitalier Universitaire De Toulouse
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Toulouse, France
Hopital Saint-Louis - Dermatology
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Paris, France
Universitätsklinikum Bonn AöR
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Bonn, Germany
Universitätsmedizin Mainz
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Mainz, Germany
Klinikum Der Universität München - Campus Innenstadt - Dermatologie und Allergologie
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München, Germany
Klinikum der Johann-Wolfgang Goethe-Universität
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Frankfurt, Germany
Eberhard-Karls Universitaet Tuebingen - Universitaets Hautkl
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Tuebingen, Germany
Universitätsklinikum Münster
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Münster, Germany
Centrum Medyczne DERMED
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Łódź, Poland