PRISM Study-Pruritus Relief Through Itch Scratch Modulation

Study Overview
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Brief Summary
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To investigate the anti-pruritic efficacy and safety of Nalbuphine Extended Release (ER) (NAL ER) tablets in Prurigo Nodularis. Subjects will be randomized to NAL ER (or matching placebo) with the primary endpoint evaluation at Week 14. During the open label extension, subjects who received NAL ER will continue on NAL ER and subjects who received placebo will crossover to NAL ER.

Detailed Description
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This is a randomized, double-blinded, placebo-controlled, 2-arm study with an open label extension period following double-blind treatment, to investigate the anti-pruritic efficacy and safety of Nalbuphine Extended Release (ER) (NAL ER) tablets. Subjects will be randomized to NAL ER (2-week titration followed by 162 mg twice daily [BID] for 12 weeks) or matching placebo (14 weeks duration), with the primary endpoint evaluation at Week 14. During the open label extension, subjects who received NAL ER will continue on NAL ER total treatment duration 52 weeks including titration and subjects who received placebo will crossover to Nalbuphine ER Upon discontinuation of investigational product, all subjects will complete a 2-week off treatment Safety Follow-up Period, regardless of when and why the subject discontinued study treatment.

Official Title
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A Phase 2b/3, Randomized, Double-Blind, Placebo-Controlled, 2-Arm , Efficacy and Safety Study in Prurigo Nodularis (PN) With Nalbuphine ER Tablets for Pruritus Relief Through Itch Scratch Modulation (PRISM Study)

Conditions
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Prurigo Nodularis

Intervention / Treatment
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* Drug: Nalbuphine ER Tablets
* Other: Matching Placebo Tablets
* Drug: Nalbuphine ER Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals diagnosed with generalized nodular PN, covering 2 separate body parts, and 10 or more pruriginous nodules Severe itch due to PN Age 18 years and older at the time of consent, and a life expectancy of at least 18 months. Individuals using antidepressants must be on a stable dose for a minimum of 4 weeks prior to screening. Exclusion Criteria: Pruritus due to localized PN (only one body part affected), or less than 10 nodules Active, uncontrolled, pruritic dermatoses in need of treatment (such as atopic dermatitis or bullous pemphigoid for example). Unresolved acute secondary dermatoses active (unresolved) in the last (a) 4 weeks: localized contact dermatitis, environmental exposures, superficial burns, or viral exanthems; (b) 8 weeks: skin or environmental infestations, such as scabies, lice, or bed bugs. Other non-dermatologic diseases that could be a potential cause of concomitant pruritus (e.g., thyroid disease, celiac disease, hepatitis C virus [HCV]) must either have resolved, been successfully treated (i.e., HCV RNA negative) or must be successfully managed with stable, optimized treatment (e.g., thyroid replacement, dietary management with resolution of symptoms, respectively) for at least 3 months prior to screening History of a major psychiatric disorder such as bipolar disorder or schizophrenia. History of active substance abuse in the last 3 years. Known intolerance (GI, CNS symptoms) or hypersensitivity/drug allergy to opioids. Use of certain concomitant medications and treatments within a period prior to the study, or requirement for these medications during the study: Potential subjects taking opiates, gabapentin, pregabalin, calcineurin inhibitors, cannabinoid agonists, capsaicin, cryosurgery, topical doxepin, thalidomide or methotrexate, topical antihistamines or topical corticosteroids require a 14-day washout. Within 4 weeks prior to screening: ultraviolet (UV)-therapy, exposure to any investigational medication, including placebo Within 3 months prior to screening: Non-insulin biologics (including monoclonal antibodies) that modify the immune system, Individuals taking monoamine oxidase inhibitors are excluded, as concomitant opiate use may increase the risk for serotonin syndrome. Myocardial infarction or acute coronary syndrome within the previous 3 months, as reported by the subject. Individuals with prolonged QTcF Individuals with HIV can be included if they meet the following criteria: (a) currently on a stable (> 6 months stable use) and well tolerated highly active antiretroviral therapy regimen; (b) CD4 count > 500 cells/mL; and (c) HIV ribonucleic acid (RNA) < 50 copies/mL documented for at least 6 months prior to enrollment.

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: Crossover Assignment
Interventional Model Description: Randomized, double-blinded, placebo-controlled, 2-arm study with an open label extension period following double-blind treatment.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>162 mg nalbuphine ER tablets, BID | Drug: Nalbuphine ER Tablets<br>* Active Nalbuphine ER Tablets<br>* Other names: NAL ER Tablets;|
| Placebo Comparator: Placebo<br>Matching placebo tablets | Other: Matching Placebo Tablets<br>* Matching Tablets with no active substance<br>|
| Experimental: Open Label Extension<br>162 mg nalbuphine ER tablets, BID | Drug: Nalbuphine ER Tablets<br>* Open Label Extension<br>* Other names: NAL ER Tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of percentage of responders by arm | To evaluate the effect of NAL ER on itch as assessed by the percentage of Responders ('response' is defined as a ≥ 4-point reduction in the 7-day average Worst Itch - Numerical Rating Scale [WI-NRS]) | 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline for itch-related quality of life: ItchyQoL total score | To evaluate the effect of NAL ER on itch-related quality of life as assessed by the ItchyQoL total score | 14 weeks | 
| Change from baseline for Prurigo Nodularis skin lesions | To evaluate the effect of NAL ER on Prurigo Nodularis (PN) skin lesions as assessed by the Prurigo Activity Score (PAS) Question 5a | 14 weeks | 
| Change from baseline for sleep disturbance | To evaluate the effect of NAL ER on sleep as assessed by the PROMIS Sleep Disturbance Short Form 8a | at week 14 |