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

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)

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.

Study Overview

• Status: Completed
• Conditions: Prurigo Nodularis
• Intervention / Treatment: Drug: Nalbuphine ER Tablets; Other: Matching Placebo Tablets; Drug: Nalbuphine ER Tablets

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
• Enrollment (Actual): 353
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Study Site 401
  • Linz, Austria, 4020
    • Study Site 402
• France
  • Brest, France, 29609
    • Study Site 501
  • Paris, France, 75010
    • Study Site 502
• Germany
  • Bad Bentheim, Germany, 48455
    • Study Site 205
  • Berlin, Germany, 10117
    • Study Site 216
  • Berlin, Germany, 10247
    • Study Site 209
  • Berlin, Germany, 10789
    • Study Site 208
  • Cologne, Germany, 50937
    • Study Site 219
  • Düsseldorf, Germany, 40225
    • Study Site 221
  • Hamburg, Germany, 20246
    • Study Site 215
  • Hamburg, Germany, 22391
    • Study Site 222
  • Heidelberg, Germany, 69115
    • Study Site 212
  • Kiel, Germany, 24105
    • Study Site 214
  • Muenchen, Germany, 80802
    • Study Site 220
  • Stuttgart, Germany, 70178
    • Study Site 206
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
      • Study Site 204
  • North Rhine-Westphal
    • Münster, North Rhine-Westphal, Germany, 48149
      • Study Site 202
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • Study Site 201
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Study Site 213
• Poland
  • Białystok, Poland, 15-453
    • Study Site 304
  • Katowice, Poland, 40-648
    • Study Site 306
  • Krakow, Poland, 31-559
    • Study Site 316
  • Kraków, Poland, 31-302
    • Study Site 308
  • Lublin, Poland, 20-406
    • Study Site 314
  • Ostrowiec Świętokrzyski, Poland, 27-400
    • Study Site 305
  • Poznań, Poland, 60-529
    • Study Site 313
  • Poznań, Poland, 60-848
    • Study Site 315
  • Rzeszów, Poland, 35055
    • Study Site 303
  • Warsaw, Poland, 01-142
    • Study Site 310
  • Warsaw, Poland, 01-817
    • Study Site 301
  • Warsaw, Poland, 02-962
    • Study Site 312
  • Wrocław, Poland, 50566
    • Study Site 302
  • Łódź, Poland, 90-265
    • Study Site 309
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Study site 151
  • California
    • Fremont, California, United States, 94538
      • Study site 121
    • Laguna Niguel, California, United States, 92677
      • Study site 157
    • North Hollywood, California, United States, 91606
      • Study site 141
    • San Francisco, California, United States, 94115
      • Study site 130
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Study site 128
  • Florida
    • Boca Raton, Florida, United States, 33433
      • Study site 138
    • Orlando, Florida, United States, 32819
      • Study site 158
    • South Miami, Florida, United States, 33143
      • Study site 108
    • Tampa, Florida, United States, 33615
      • Study site 142
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Study site 102
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Study site 136
    • Brighton, Massachusetts, United States, 02135
      • Study site 153
  • Michigan
    • Ann Arbor, Michigan, United States, 48103
      • Study site 143
    • Troy, Michigan, United States, 48084
      • Study site 139
  • Missouri
    • Saint Joseph, Missouri, United States, 64506
      • Study site 118
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Study Site 144
    • Las Vegas, Nevada, United States, 89119
      • Study site 146
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • Study site 109
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Study site 159
  • New York
    • Stony Brook, New York, United States, 11794
      • Study site 134
  • North Carolina
    • Wilmington, North Carolina, United States, 28411
      • Study site 101
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Study Site 122
    • Cleveland, Ohio, United States, 44106
      • Study site 120
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Study site 132
    • Philadelphia, Pennsylvania, United States, 19103
      • Study site 106
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Study site 131
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Study site 147
    • Charleston, South Carolina, United States, 29425-8908
      • Study site 107
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Study site 140
    • Knoxville, Tennessee, United States, 37917
      • Study site 145
  • Texas
    • Austin, Texas, United States, 78705
      • Study site 137
    • Webster, Texas, United States, 77598
      • Study site 103
  • Utah
    • West Jordan, Utah, United States, 84088
      • Study site 150
  • Washington
    • Spokane, Washington, United States, 99202
      • Study site 135
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Study Site 148

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Trevi Therapeutics
• Investigators: Study Director: David Clark, MD, Trevi Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2018
• Primary Completion (Actual): May 10, 2022
• Study Completion (Actual): February 24, 2023

Study Registration Dates

• First Submitted: March 22, 2018
• First Submitted That Met QC Criteria: April 10, 2018
• First Posted (Actual): April 13, 2018

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: May 2, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Manifestations; Pruritus; Prurigo; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Nalbuphine
• Other Study ID Numbers: TR11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No