PRISM Study-Pruritus Relief Through Itch Scratch Modulation (PRISM)

• ClinicalTrials.gov Identifier: NCT03497975
• Recruitment Status: Completed
• First Posted: April 13, 2018
• Last Update Posted: May 6, 2023
• Sponsor: Trevi Therapeutics
• Information provided by (Responsible Party): Trevi Therapeutics

Tracking Information

• First Submitted Date: March 22, 2018
• First Posted Date: April 13, 2018
• Last Update Posted Date: May 6, 2023
• Actual Study Start Date: August 7, 2018
• Actual Primary Completion Date: May 10, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 15, 2019)

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 ≥ 4-point reduction in the 7-day average Worst Itch - Numerical Rating Scale [WI-NRS])

Original Primary Outcome Measures (submitted: April 10, 2018)

A 4 point reduction in the Worst Itch Numerical Rating Scale (WINRS) at Week 14. (Responder = at least an improvement of 4 in WINRS score) [ Time Frame: 14 weeks ]

Comparison of percentage responders by arm;

Current Secondary Outcome Measures (submitted: July 15, 2019)

• 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
• 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
• 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

Original Secondary Outcome Measures (submitted: April 10, 2018)

• The change from baseline up to week 14 for WINRS up to Week 14 [ Time Frame: 14 weeks ]
  assessment of improvement from baseline
• The change from baseline up to week 14 for itchyQOL up to Week 14 [ Time Frame: 14 weeks ]
  assessment of improvement from baseline
• PBI-P, a simple analysis of covariance (ANCOVA) will be used to assess the change from baseline at Week 14. [ Time Frame: 14 weeks ]
  assessment of a subject's perception of their disease before and after treatment
• PAS: 1-category improvement from baseline in lesions with excoriations. [ Time Frame: at week 14 and at week 52 ]
  Assessment of number of subjects with 1-category improvement from baseline in lesions with excoriations.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PRISM Study-Pruritus Relief Through Itch Scratch Modulation
• 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)
• Brief Summary: 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: 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.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

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

• Condition: Prurigo Nodularis

Intervention

• Drug: Nalbuphine ER Tablets
  Active Nalbuphine ER Tablets
  Other Name: NAL ER Tablets
• Other: Matching Placebo Tablets
  Matching Tablets with no active substance
• Drug: Nalbuphine ER Tablets
  Open Label Extension
  Other Name: NAL ER Tablets

Study Arms

• Experimental: Active
  162 mg nalbuphine ER tablets, BID
  Intervention: Drug: Nalbuphine ER Tablets
• Placebo Comparator: Placebo
  Matching placebo tablets
  Intervention: Other: Matching Placebo Tablets
• Experimental: Open Label Extension
  162 mg nalbuphine ER tablets, BID
  Intervention: Drug: Nalbuphine ER Tablets

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 4, 2023): 353
• Original Estimated Enrollment (submitted: April 10, 2018): 240
• Actual Study Completion Date: February 24, 2023
• Actual Primary Completion Date: May 10, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, France, Germany, Poland, United States

Administrative Information

• NCT Number: NCT03497975
• Other Study ID Numbers: TR11
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Trevi Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Trevi Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: David Clark, MD; Trevi Therapeutics

• PRS Account: Trevi Therapeutics
• Verification Date: January 2023