PRISM Study-Pruritus Relief Through Itch Scratch Modulation

NCT03497975 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: TR112018-001219-53
• Study Type: interventional
• Target: 353
• Locations: 5 countries
• Sites: 70

Brief Summary

To investigate the anti-pruritic efficacy and safety of Nalbuphine Extended Release (ER) (NAL ER) tablets in Prurigo Nodularis. Participants were randomized to NAL ER (or matching placebo) with the primary endpoint evaluation at Week 14. During the open label extension, participants who received NAL ER were continued on NAL ER and participants who received placebo would then shift to NALER.

Conditions

Prurigo Nodularis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With ≥ 4- Point Decrease in 7-day Average Worst Itch - Numerical Rating Scale (WI-NRS) up to Week 14

  The NRS is a patient related outcome (PRO) instrument, designed to quantify the intensity of worst itching experienced during a 24-hour period, and can be applied and validated either with reference to the average itch or to the absolute worst itch (WI-NRS) over that 24-hour period. WI-NRS is a set of boxes, one for each number, from 0 (no itching) to 10 (worst possible itching). Higher scores indicate worst itching experience. Responder was defined as a participant with a ≥4-point decrease in the 7-day average WI-NRS from baseline to Week 14.

  Baseline up to Week 14

Secondary Outcomes (11)

• Change From Baseline in Itch-related Quality of Life (ItchyQoL) Total Score at Week 14

  Baseline, Week 14

• Change From Baseline in Prurigo Activity Score (PAS) Assessed by the Percentage of Participants With 1-Category Improvement in the Percentage of Pruriginous Lesions With Excoriations/Crusts (Item 5a) at Week 14

  Baseline, Week 14

• Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form 8a at Week 14

  Baseline, Week 14

• Change From Baseline in 7-Day Average WI-NRS to Week 14

  Baseline, Week 14

• Change From Baseline in PAS Assessed by the Percentage of Participants With 1-Category Improvement in the Percentage of Healed Lesions (Item 5b) at Week 14

  Baseline, Week 14

Study Arms (2)

NAL ER

EXPERIMENTAL

During the double-blind (DB) period, participants were titrated over 2 weeks to NAL ER 162 mg, orally, twice daily (BID), followed by 162 mg, orally, BID, for 12 weeks. During the open label extension (OLE) period, participants perceived a titration period of 2 weeks, and continued to receive NAL ER 162 mg, orally, BID, for 38 weeks in total.

Drug: Nalbuphine ER Tablets

Placebo

PLACEBO COMPARATOR

During the DB period, participants perceived a titration period of 2 weeks during which they received placebo to match the active titration period, followed by placebo, orally, BID, for 12 weeks. During the OLE period, participants were titrated over 2 weeks to NAL ER 162 mg, orally, BID, which they received for 38 weeks (including titration).

Drug: Nalbuphine ER Tablets; Drug: Placebo Tablets

Interventions

Nalbuphine ER Tablets DRUG

Active Nalbuphine ER Tablets

Also known as: NAL ER Tablets

NAL ER; Placebo

Placebo Tablets DRUG

Placebo matching NAL ER with no active substance

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Participants with a history of acute secondary dermatoses within the preceding 6 months may enroll only if the dermatosis has resolved completely as follows per medical history or participant self-report and current clinical assessment: (a) Localized contact dermatitis, environmental exposures, superficial burns, or viral exanthems must have been resolved for at least 4 weeks prior to screening. (b) Skin or environmental infestations, such as scabies, lice, or bed bugs, must have been resolved for at least 8 weeks prior to screening.
• Any identified systemic, non-dermatologic disease 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 \[i.e., HCV ribonucleic acid (RNA) negative\], 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.
• Participants who are human immunodeficiency virus (HIV) positive may enroll if they meet the following criteria: (a) currently on a stable (\> 6 months stable use) and well tolerated highly active antiretroviral therapy regimen; (b) cluster of differentiation 4 (CD4) count \> 500 cells/mL; and (c) HIV ribonucleic acid (RNA) \< 50 copies/mL documented for at least 6 months prior to enrollment.

You may not qualify if:

• 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).
• History of a major psychiatric disorder such as bipolar disorder or schizophrenia. History of active substance abuse in the last 3 years.
• Known intolerance \[gastrointestinal (GI), central nervous system (CNS) symptoms\] 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 participants 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 participant.
• Individuals with prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF).

Sponsors & Collaborators

• Trevi Therapeutics: lead

Study Sites (70)

Study Site 151

Phoenix, Arizona, 85006, United States

Location

Study Site 121

Fremont, California, 94538, United States

Location

Study Site 157

Laguna Niguel, California, 92677, United States

Location

Study Site 141

North Hollywood, California, 91606, United States

Location

Study Site 130

San Francisco, California, 94115, United States

Location

Study Site 128

Washington D.C., District of Columbia, 20037, United States

Location

Study Site 138

Boca Raton, Florida, 33433, United States

Location

Study Site 158

Orlando, Florida, 32819, United States

Location

Study Site 108

South Miami, Florida, 33143, United States

Location

Study Site 142

Tampa, Florida, 33615, United States

Location

Study Site 102

Rockville, Maryland, 20850, United States

Location

Study Site 136

Boston, Massachusetts, 02114, United States

Location

Study Site 153

Brighton, Massachusetts, 02135, United States

Location

Study Site 143

Ann Arbor, Michigan, 48103, United States

Location

Study Site 139

Troy, Michigan, 48084, United States

Location

Study Site 118

Saint Joseph, Missouri, 64506, United States

Location

Study Site 144

Henderson, Nevada, 89052, United States

Location

Study Site 146

Las Vegas, Nevada, 89119, United States

Location

Study Site 109

Portsmouth, New Hampshire, 03801, United States

Location

Study Site 159

Hackensack, New Jersey, 07601, United States

Location

Study Site 134

Stony Brook, New York, 11794, United States

Location

Study Site 101

Wilmington, North Carolina, 28411, United States

Location

Study Site 122

Cincinnati, Ohio, 45219, United States

Location

Study Site 120

Cleveland, Ohio, 44106, United States

Location

Study Site 132

Hershey, Pennsylvania, 17033, United States

Location

Study Site 106

Philadelphia, Pennsylvania, 19103, United States

Location

Study Site 131

Johnston, Rhode Island, 02919, United States

Location

Study Site 147

Charleston, South Carolina, 29407, United States

Location

Study Site 107

Charleston, South Carolina, 29425-8908, United States

Location

Study Site 140

Chattanooga, Tennessee, 37421, United States

Location

Study Site 145

Knoxville, Tennessee, 37917, United States

Location

Study Site 137

Austin, Texas, 78705, United States

Location

Study Site 103

Webster, Texas, 77598, United States

Location

Study Site 150

West Jordan, Utah, 84088, United States

Location

Study Site 135

Spokane, Washington, 99202, United States

Location

Study Site 148

Morgantown, West Virginia, 26505, United States

Location

Study Site 401

Graz, 8036, Austria

Location

Study Site 402

Linz, 4020, Austria

Location

Study Site 501

Brest, 29609, France

Location

Study Site 502

Paris, 75010, France

Location

Study Site 204

Frankfurt am Main, Hesse, 60590, Germany

Location

Study Site 202

Münster, North Rhine-Westphal, 48149, Germany

Location

Study Site 201

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Study Site 213

Dresden, Saxony, 01307, Germany

Location

Study Site 205

Bad Bentheim, 48455, Germany

Location

Study Site 216

Berlin, 10117, Germany

Location

Study Site 209

Berlin, 10247, Germany

Location

Study Site 208

Berlin, 10789, Germany

Location

Study Site 219

Cologne, 50937, Germany

Location

Study Site 221

Düsseldorf, 40225, Germany

Location

Study Site 215

Hamburg, 20246, Germany

Location

Study Site 222

Hamburg, 22391, Germany

Location

Study Site 212

Heidelberg, 69115, Germany

Location

Study Site 214

Kiel, 24105, Germany

Location

Study Site 220

München, 80802, Germany

Location

Study Site 206

Stuttgart, 70178, Germany

Location

Study Site 304

Bialystok, 15-453, Poland

Location

Study Site 306

Katowice, 40-648, Poland

Location

Study Site 308

Krakow, 31-302, Poland

Location

Study Site 316

Krakow, 31-559, Poland

Location

Study Site 309

Lodz, 90-265, Poland

Location

Study Site 314

Lublin, 20-406, Poland

Location

Study Site 305

Ostrowiec Świętokrzyski, 27-400, Poland

Location

Study Site 313

Poznan, 60-529, Poland

Location

Study Site 315

Poznan, 60-848, Poland

Location

Study Site 303

Rzeszów, 35055, Poland

Location

Study Site 310

Warsaw, 01-142, Poland

Location

Study Site 301

Warsaw, 01-817, Poland

Location

Study Site 312

Warsaw, 02-962, Poland

Location

Study Site 302

Wroclaw, 50566, Poland

Location

Results Point of Contact

• Title: Chief Development Officer
• Organization: Trevi Therapeutics, Inc.

info@trevitherapeutics.com

203-304-2499

Study Officials

• Chief Development Officer

  Trevi Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2018
• First Posted: April 13, 2018
• Study Start: August 7, 2018
• Primary Completion: May 10, 2022
• Study Completion: February 24, 2023
• Last Updated: June 24, 2025
• Results First Posted: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (16); PL (14); FR (2); AU (2); US (36)