Prurigo Nodularis (PRISM Study)

Study Description

Brief Summary

To investigate the anti-pruritic efficacy and safety of Nalbuphine 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.

Condition or Disease

Prurigo Nodularis

Detailed Description

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 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.

Study Design

Study Type: Interventional  (Clinical Trial)
Estimated Enrollment: 360 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Randomized, double-blinded, placebo-controlled, 2-arm study with an open label extension period following double-blind treatment.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Matching Placebo
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date: August 7, 2018
Estimated Primary Completion Date : May 8, 2022
Estimated Study Completion Date : February 28, 2023

Outcome Measures

Primary Outcome Measures

  1. Comparison of percentage of responders by arm [ Time Frame: 14 weeks ]
    To evaluate the effect of NAL ER on itch as assessed by the percentage of Responders (‘response’ is defined as a ‚Č• 4-point reduction in the 7-day average Worst Itch – Numerical Rating Scale [WI-NRS])

Secondary Outcome Measures

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

Eligibility Criteria

Ages Eligible for Study: 18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No

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.

ADDITIONAL DETAILS