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

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

Conditions
-----------------
Prurigo Nodularis

Intervention / Treatment
-----------------
* Drug: Nemolizumab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical diagnosis of PN for at least 6 months with: Pruriginous nodular lesions on upper limbs, trunk, and/or lower limbs, at least 20 nodules on the entire body with a bilateral distribution and 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: At the screening visit (Visit 1): PP NRS score is >= 7.0 for the 24-hour period immediately preceding the screening visit. 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 adequate and approved method of contraception throughout the study and for 12 weeks after the last study drug injection Exclusion Criteria: Body weight less than (<) 30 kg Chronic pruritus resulting from another active condition other than PN, such as but not limited to scabies, lichen simplex chronicus, psoriasis, atopic dermatitis, contact dermatitis, acne, folliculitis, lichen planus, habitual picking/excoriation disorder, sporotrichosis, bullous autoimmune disease, end-stage renal disease, or cholestatic liver disease (example [eg] primary biliary cirrhosis) or diabetes mellitus or thyroid disease that is not adequately treated, as per standard of care 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 Neuropathic and psychogenic pruritus such as but not limited to notalgia paresthetica, brachioradial pruritus, small fiber neuropathy, skin picking syndrome, or delusional parasitosis Requiring rescue therapy for PN during the screening period or expected to require rescue therapy within 4 weeks following the baseline visit 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
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nemolizumab<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). Participants weighing greater than or equal to (>=) 90 kg will receive two SC injections of 60 mg nemolizumab at baseline (no loading dose) and two SC injections Q4W throughout the treatment period of 16 weeks. | Drug: Nemolizumab<br>* Participants will receive either 30 mg or 60 mg dose of nemolizumab as SC injection.<br>* Other names: CD14152;|
| Placebo Comparator: Placebo<br>Participants weighing < 90 kg will receive two SC injections of matching placebo at baseline, then one SC injection Q4W. Participants weighing >= 90 kg will receive two SC injections of matching placebo at baseline, then two SC injections Q4W throughout the treatment period of 16 weeks. | Drug: Placebo<br>* Participants will receive matching placebo as SC injection.<br>|

What is the study measuring?
-----------------
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 Numeric Rating Scale (PP 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 Week 24 | 
| Proportion of Participants with an Improvement of >= 4 from Baseline in PP NRS at Week 4 |  | Week 4 | 
| Proportion of Participants with Less than (<) 2 PP NRS at Week 16 |  | Week 16 | 
| Proportion of Participants with an Improvement of >= 4 from Baseline in Sleep Disturbance (SD) Numeric Rating Scale (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 < 2 PP NRS at Week 4 |  | Week 4 | 
| IGA Success Rate at Each Visit Through Week 16 |  | At each visit through Week 16 | 
| Percentage of Pruriginous Lesions with Excoriations/Crusts (Prurigo Activity Score [PAS] item 5a) at Each Visit Through Week 16 | 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 16 | 
| Percentage of Healed Prurigo Lesions (PAS Item 5b) at Each Visit Through Week 16 | 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 16 | 
| Change from Baseline in Number of Lesions in Representative Area (PAS Item 4) at Each Visit Through Week 16 | PAS Item 4 is measure of number of lesions in representative area. | Baseline, at each visit through Week 16 | 
| Proportion of Participants with an Improvement of >=4 from Baseline in PP NRS Through Week 16 |  | Through Week 16 | 
| Proportion of Participants with PP NRS < 2 from Baseline Through Week 16 |  | Through Week 16 | 
| Proportion of Participants with PP NRS < 3 from Baseline Through Week 16 |  | Through Week 16 | 
| Absolute Change from Baseline in PP NRS Through Week 16 |  | Baseline, through Week 16 | 
| Percent Change from Baseline in PP NRS Through Week 16 |  | Baseline, through Week 16 | 
| Proportion of Participants with an Improvement of >= 4 from Baseline in Average Pruritus (AP) Numeric Rating Scale (NRS) Through Week 16 | AP NRS is an 11-point scale (0 to10) where 0 is no itch and 10 is the worst itch imaginable. | Through Week 16 | 
| Proportion of Participants with AP NRS < 2 from Baseline Through Week 16 |  | Through Week 16 | 
| Absolute Change from Baseline in AP NRS Through Week 16 |  | Baseline, through Week 16 | 
| Percent Change from Baseline in AP NRS Through Week 16 |  | Baseline, through Week 16 | 
| Proportion of Participants with an Improvement of >= 4 from Baseline in Sleep Disturbance (SD) Numeric Rating Scale (NRS) Through 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. | Through Week 16 | 
| Absolute Change from Baseline in SD NRS Through Week 16 |  | Baseline, through Week 16 | 
| Percent Change from Baseline in SD NRS Through Week 16 |  | Baseline, through Week 16 | 
| Change from Baseline in Sleep Onset Latency Through Week 16 | Change from baseline in sleep onset latency based on recordings from participant's sleep diary. | Baseline, through Week 16 | 
| Change from Baseline in Wakefulness After Sleep Onset (WASO) Through Week 16 | 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 16 | 
| Change from Baseline in Total Awake Time and Sleep Time Through Week 16 |  | Baseline, through Week 16 | 
| Change from Baseline in Sleep Efficiency Through Week 16 | The Sleep Efficiency Index 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 16 | 
| Change from Baseline in WASO related to PN Through Week 16 |  | Baseline, through Week 16 | 
| Change from Baseline in Number of WASO related to PN Through Week 16 |  | Baseline, through Week 16 | 
| Change from Baseline in PN-associated Pain Frequency Through Week 16 | The pain frequency will be assessed on a 6 point scale of 0 to 5 where 0 = never, 1 = less than once a week, 2 = 1-2 days a week, 3 = 3-4 days a week, and 4 = 5-6 days a week, 5 = every day. | Baseline, through Week 16 | 
| Change from Baseline in PN-associated Pain Intensity Through Week 16 | The pain intensity will be assessed on a scale of 0 to 10, with 0 being no pain and 10 being the worst unbearable pain. | Baseline, through Week 16 | 
| Proportion of Participants Reporting low Disease Activity (Clear, Almost clear, or Mild) Based on Patient Global Assessment of Disease (PGAD) at Week 16 | 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 16 | 
| Proportion of Participants Satisfied with Study Treatment (Good, Very good, or Excellent) Based on Patient Global Assessment of Treatment (PGAT) at Week 16 | 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 16 | 
| Proportion of Participants with an Improvement of >= 4 in Dermatology Life Quality Index (DLQI) Through Week 16 | 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). A higher total score indicates a poorer quality of life (QoL). | Through Week 16 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) Through Week 16 |  | Baseline, through Week 16 | 
| Change from Baseline in Hospital Anxiety and Depression Scale (HADS) for each Subscale (Depression and Anxiety) at Week 16 | Hospital Anxiety and Depression Scale (HADS) is a 14-question validated questionnaire completed by the participant for each subscale (i.e. depression and anxiety). Each 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 16 | 
| Change from Baseline in EuroQoL 5-Dimension (EQ-5D) at Week 16 | The EQ-5D instrument is a validated questionnaire, completed by the participant that consists of 2 parts. The first part consists of 5 multiple choice QoL questions and the second is a 100 point visual analogue scale (VAS) with 0 being Worst imaginable health state and 100 being Best imaginable health state. | Baseline, Week 16 | 
| Observed Ctrough of Nemolizumab in Serum |  | Pre-infusion, Post infusion on Day 8, 29, 57, 85, 113, 169 | 
| Number of Participants with Positive Anti-drug antibody (ADA) for Nemolizumab |  | Baseline, Day 57, Day 113/ Early Termination (ET) | 
| Proportion of subjects with PP NRS improvement ≥ 4 from baseline and IGA success |  | Week 16 | 
| Nemolizumab (CD14152) serum concentrations |  | Week 4, 8, 12, 16, 24, ET |