An Efficacy and Safety Study of Nemolizumab (CD14152) in Participants With Prurigo Nodularis

Study Overview
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Brief Summary
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The primary objective is to assess the efficacy of nemolizumab (CD14152) compared to placebo in participants greater than or equal to (>=) 18 years of age with prurigo nodularis (PN) after a 16 week treatment period.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Nemolizumab (CD14152) in Subjects With Prurigo Nodularis

Conditions
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Prurigo Nodularis

Intervention / Treatment
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* Drug: Nemolizumab 30 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of PN for at least 6 months with: (a) Pruriginous nodular lesions on upper limbs, trunk, and/or lower limbs; (b) At least 20 nodules on the entire body with a bilateral distribution; (c) Investigator Global Assessment (IGA) score >= 3 (based on the IGA scale ranging from 0 to 4, in which 3 is moderate and 4 is severe) at both the screening and baseline visits Severe pruritus defined as follows on the PP NRS: (a) at the screening visit (Visit 1): PP NRS score is >= 7.0 for the 24-hour period immediately preceding the screening visit; (b) at the baseline visit (Visit 2): Mean of the daily intensity of the PP NRS score is >= 7.0 over the previous week Female participants of childbearing potential (that is [i.e,], fertile, following menarche and until becoming post-menopausal unless permanently sterile) must agree to use at least 1 effective and approved method of contraception throughout the study and for 12 weeks after the last study drug injection Participant is willing and able to comply with all of the time commitments and procedural requirements of the clinical study protocol, including daily diary recordings by the participant using an electronic handheld device provided for this study Exclusion Criteria: Body weight < 30 kilogram (kg) Unilateral lesions of prurigo (eg, only one arm affected) History of or current confounding skin condition (eg, Netherton syndrome, cutaneous T-cell lymphoma [mycosis fungoides or Sezary syndrome], chronic actinic dermatitis, dermatitis herpetiformis) Participants with a current medical history of chronic obstructive pulmonary disease and/or chronic bronchitis Positive serology results (hepatitis B surface antigen [HBsAg] or hepatitis B core antibody [HBcAb], hepatitis C (HCV) antibody with positive confirmatory test for HCV (eg, polymerase chain reaction [PCR]), or human immunodeficiency virus antibody) at the screening visit

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nemolizumab 30 milligram (mg)<br>Participants weighing less than (<) 90 kilogram (kg) will receive two subcutaneous (SC) injections of 30 milligrams (mg) nemolizumab (60 mg loading dose) at baseline then one SC injection once for every 4 weeks (Q4W) and participants >= 90 kg will receive two SC injections of 60 mg nemolizumab at baseline (no loading dose) and two SC injections Q4W up to 24 weeks. | Drug: Nemolizumab 30 mg<br>* Participants will receive either 30 mg or 60 mg dose of nemolizumab as SC injection.<br>|
| Placebo Comparator: Placebo<br>Participants weighing < 90 kg will receive matching placebo of two SC injections at baseline, then one SC injection Q4W and participants weighing >= 90 kg will receive matching placebo of two SC injections at baseline, then two SC injections Q4W up to 24 weeks. | Drug: Placebo<br>* Participants will receive matching placebo as SC injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants with an Improvement of Greater than or Equal to (>=) 4 from Baseline in Peak Pruritus (PP) Numeric Rating Scale (NRS) at Week 16 | PP NRS is an 11-point scale (0 to10) where 0 is no itch and 10 is the worst itch imaginable. | Week 16 | 
| Proportion of Participants with an Investigator Global Assessment (IGA) Success (Defined as an IGA of 0 [Clear] or 1 [Almost clear] and a >= 2-Point Improvement from Baseline) at Week 16 | IGA is a 5-point scale used by the investigator or trained designee to evaluate the global severity of PN. The Investigator will review the participant's skin and give a score of 0 (Clear), 1 (Almost clear), 2 (Mild), 3 (Moderate), or 4 (Severe). | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events, Treatment Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs), and Serious Adverse Events (SAEs) | An AE is defined as any untoward medical occurrence in a clinical study participant administered a medicinal product which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not it is related to the medicinal (investigational) product. | Up to 36 weeks | 
| Proportion of Participants with an Improvement of >= 4 from Baseline in PP NRS at Week 4 |  | Week 4 | 
| Proportion of Participants with PP NRS < 2 at Week 16 |  | Week 16 | 
| Proportion of Participants with an Improvement of >= 4 from Baseline in Sleep Disturbance (SD) NRS at Week 16 | SD NRS is an 11-point scale (0 to10) where 0 is no sleep loss and 10 is I did not sleep at all. | Week 16 | 
| Proportion of Participants with an Improvement of >= 4 from Baseline in SD NRS at Week 4 |  | Week 4 | 
| Proportion of Participants with PP NRS < 2 at Week 4 |  | Week 4 | 
| IGA Success Rate at Each Visit Through Week 24 |  | At Each Visit Through Week 24 | 
| Percentage of Pruriginous Lesions with Excoriations/Crusts ((Prurigo Activity Score [PAS] item 5a) at Each Visit Through Week 24 | PAS will include a count of the number of lesions in a representative area and a calculated staging (stage 0 to stage 4) based on the percentage of lesions with excoriations/crusts and healed lesions compared to all lesions. PAS item 5a reflects the current itch/scratch activity. It is used to estimate what percentage of the pruriginous legions show excoriations/crusts. 100 percent (%) = All pruriginous lesions have excoriations/crusts. | At Each Visit Through Week 24 | 
| Percentage of Healed Prurigo Lesions (PAS item 5b) at Each Visit Through Week 24 | PAS item 5b item reflects the stage of the prurigo. It is used to estimate what percentage of the pruriginous lesions have healed.100% = all pruriginous lesions have healed. | At Each Visit Through Week 24 | 
| Change from Baseline in Number of Lesions in Representative Area (PAS item 4) at Each Visit Through Week 24 | PAS Item 4 is measure of number of lesions in representative area. | Baseline, at each visit through Week 24 | 
| Proportion of Participants with an Improvement of >= 4 from Baseline in PP NRS Through Week 24 |  | Through Week 24 | 
| Proportion of Participants with PP NRS < 2 Through Week 24 |  | Through Week 24 | 
| Proportion of Participants with PP NRS < 3 Through Week 24 |  | Through Week 24 | 
| Percent Change from Baseline in PP NRS Through Week 24 |  | Baseline, through Week 24 | 
| Absolute Change from Baseline in PP NRS Through Week 24 |  | Baseline, through Week 24 | 
| Proportion of Participants with an Improvement of >= 4 from Baseline in Average Pruritus (AP) NRS Through Week 24 | AP NRS is an 11-point scale (0 to10) where 0 is no itch and 10 is the worst itch imaginable. | Through Week 24 | 
| Proportion of Participants with AP NRS < 2 from Baseline Through Week 24 |  | Through Week 24 | 
| Absolute Change from Baseline in AP NRS Through Week 24 |  | Baseline, Through Week 24 | 
| Percent Change from Baseline in AP NRS Through Week 24 |  | Baseline, Through Week 24 | 
| Proportion of Participants with an Improvement of >= 4 from Baseline in SD NRS Through Week 24 |  | Through Week 24 | 
| Absolute Change from Baseline in SD NRS Through Week 24 |  | Baseline, through Week 24 | 
| Percent Change from Baseline in SD NRS Through Week 24 |  | Baseline, through Week 24 | 
| Change from Baseline in Sleep Onset Latency Through Week 24 |  | Baseline, through Week 24 | 
| Change from Baseline in Wakefulness After Sleep Onset (WASO) Through Week 24 | Change from baseline in WASO, defined as the duration of wakefulness from the onset of persistent sleep. WASO is assessed with 3 questions: 1) How many times did you wake up due to the symptoms of prurigo nodularis (for example itching, burning), not counting the final time you woke up for the day? 2) In total, how long did the awakenings related to the symptoms of prurigo nodularis (for example itching, burning) last and 3) In total, how long did these awakenings related to other things last (for example to drink water, to go to the bathroom). | Baseline, through Week 24 | 
| Change from Baseline in Total Awake and Sleep Time Through Week 24 |  | Baseline, through Week 24 | 
| Change from Baseline in Sleep Efficiency Through Week 24 | The Sleep Efficiency is the ratio of total sleep time to time in bed. This shall be assessed by responses from the following questions from participant's sleep diary: 1) What time did you get into bed? 2) What time did you try to go to sleep? 3) How long did it take you to fall asleep? 4) What time did you wake up for the day? 5) What time did you get out of bed for the day? | Baseline, through Week 24 | 
| Change from Baseline in WASO Related to PN Through Week 24 |  | Baseline, through Week 24 | 
| Change from Baseline in Number of WASO Related to PN Through Week 24 |  | Baseline, through Week 24 | 
| Change from Baseline in PN-associated Pain Frequency Through Week 24 |  | Baseline, through Week 24 | 
| Change from Baseline in PN-associated Pain Intensity Through Week 24 |  | Baseline, through Week 24 | 
| Proportion of Participants Reporting low Disease Activity (Clear, Almost clear, or Mild) Based on Patient Global Assessment of Disease (PGAD) at Week 24 | For the PGAD, participants will be asked to rate their overall impression of their skin disease (prurigo nodularis) severity using a 5-point scale from 0=clear to 5=severe. | Week 24 | 
| Proportion of Participants Satisfied with Study Treatment (Good, Very Good, or Excellent) Based on Patient Global Assessment of Treatment (PGAT) at Week 24 | The PGAT utilizes a 5-point scale with ratings: poor, fair, good, very good, or excellent, for participants to rate the way they feel their skin disease (prurigo nodularis) is responding to the study treatment. | Week 24 | 
| Proportion of Participants with an Improvement of >= 4 in DLQI Through Week 24 | The DLQI is a validated 10-item questionnaire covering domains including symptoms/feelings, daily activities, leisure, work/school, personal relationships, and treatment. The participant will rate each question ranging from 0 (not at all) to 3 (very much) and score ranges from 0 to 30. A higher total score indicates a poorer quality of life (QoL). | Through Week 24 | 
| Change from Baseline in DLQI Through Week 24 |  | Baseline, through Week 24 | 
| Change from Baseline in Hospital Anxiety and Depression Scale (HADS) at Week 24 | HADS is a 14-question validated questionnaire completed by the participant for each subscale (i.e. depression and anxiety). Question has a multiple choice answer which is scored between 0 and 3. Questions are identified as relating to anxiety (A) or depression (D) and a summation for each area is performed leading to a total score of 0 to 21 for each area. Scores of 0 to 7 are considered normal, 8 to 10 are borderline, and >= 11 indicates clinical effects. | Baseline, Week 24 | 
| Change from Baseline in EuroQoL 5-Dimension (EQ-5D) at Week 24 | The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating health today with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). | Baseline, Week 24 | 
| Area Under Curve (AUC) of Nemolizumab in the Serum |  | Pre-infusion, Post infusion on Day 29, 57, 85, 113, 169, 225 | 
| Trough Level (Ctrough) of Nemolizumab in the Serum |  | Pre-infusion, Post infusion on Day 29, 57, 85, 113, 169, 225 | 
| Maximum Serum Concentration (Cmax) of Nemolizumab in Serum |  | Pre-infusion, Post infusion on Day 29, 57, 85, 113, 169, 225 | 
| Half-Life (t1/2) of Nemolizumab in Serum |  | Pre-infusion, Post infusion on Day 29, 57, 85, 113, 169, 225 | 
| Observed Ctrough of Nemolizumab in Serum |  | Pre-infusion, Post infusion on Day 29, 57, 85, 113, 169, 225 | 
| Number of Participants with Positive Anti-drug antibody (ADA) for Nemolizumab |  | Baseline, Day 57, Day 113, Day 169/Early Termination |