PRISM Study-Pruritus Relief Through Itch Scratch Modulation

NCT ID: NCT03497975

Last Updated: 2025-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 353 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-07
• Study Completion Date: 2023-02-24

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

NAL ER

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.

Group Type: EXPERIMENTAL

Nalbuphine ER Tablets

Intervention Type: DRUG

Active Nalbuphine ER Tablets

Placebo

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).

Group Type: PLACEBO_COMPARATOR

Nalbuphine ER Tablets

Intervention Type: DRUG

Active Nalbuphine ER Tablets

Placebo Tablets

Intervention Type: DRUG

Placebo matching NAL ER with no active substance

Interventions

Nalbuphine ER Tablets

Active Nalbuphine ER Tablets

Intervention Type: DRUG

Placebo Tablets

Placebo matching NAL ER with no active substance

Intervention Type: DRUG

Other Intervention Names

NAL ER Tablets

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.
• 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.

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).
• 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Trevi Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chief Development Officer

Role: STUDY_DIRECTOR

Trevi Therapeutics

Locations

Study Site 151

Phoenix, Arizona, United States

Study Site 121

Fremont, California, United States

Study Site 157

Laguna Niguel, California, United States

Study Site 141

North Hollywood, California, United States

Study Site 130

San Francisco, California, United States

Study Site 128

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

Study Site 138

Boca Raton, Florida, United States

Study Site 158

Orlando, Florida, United States

Study Site 108

South Miami, Florida, United States

Study Site 142

Tampa, Florida, United States

Study Site 102

Rockville, Maryland, United States

Study Site 136

Boston, Massachusetts, United States

Study Site 153

Brighton, Massachusetts, United States

Study Site 143

Ann Arbor, Michigan, United States

Study Site 139

Troy, Michigan, United States

Study Site 118

Saint Joseph, Missouri, United States

Study Site 144

Henderson, Nevada, United States

Study Site 146

Las Vegas, Nevada, United States

Study Site 109

Portsmouth, New Hampshire, United States

Study Site 159

Hackensack, New Jersey, United States

Study Site 134

Stony Brook, New York, United States

Study Site 101

Wilmington, North Carolina, United States

Study Site 122

Cincinnati, Ohio, United States

Study Site 120

Cleveland, Ohio, United States

Study Site 132

Hershey, Pennsylvania, United States

Study Site 106

Philadelphia, Pennsylvania, United States

Study Site 131

Johnston, Rhode Island, United States

Study Site 147

Charleston, South Carolina, United States

Study Site 107

Charleston, South Carolina, United States

Study Site 140

Chattanooga, Tennessee, United States

Study Site 145

Knoxville, Tennessee, United States

Study Site 137

Austin, Texas, United States

Study Site 103

Webster, Texas, United States

Study Site 150

West Jordan, Utah, United States

Study Site 135

Spokane, Washington, United States

Study Site 148

Morgantown, West Virginia, United States

Study Site 401

Graz, , Austria

Study Site 402

Linz, , Austria

Study Site 501

Brest, , France

Study Site 502

Paris, , France

Study Site 204

Frankfurt am Main, Hesse, Germany

Study Site 202

Münster, North Rhine-Westphal, Germany

Study Site 201

Mainz, Rhineland-Palatinate, Germany

Study Site 213

Dresden, Saxony, Germany

Study Site 205

Bad Bentheim, , Germany

Study Site 216

Berlin, , Germany

Study Site 209

Berlin, , Germany

Study Site 208

Berlin, , Germany

Study Site 219

Cologne, , Germany

Study Site 221

Düsseldorf, , Germany

Study Site 215

Hamburg, , Germany

Study Site 222

Hamburg, , Germany

Study Site 212

Heidelberg, , Germany

Study Site 214

Kiel, , Germany

Study Site 220

München, , Germany

Study Site 206

Stuttgart, , Germany

Study Site 304

Bialystok, , Poland

Study Site 306

Katowice, , Poland

Study Site 308

Krakow, , Poland

Study Site 316

Krakow, , Poland

Study Site 309

Lodz, , Poland

Study Site 314

Lublin, , Poland

Study Site 305

Ostrowiec Świętokrzyski, , Poland

Study Site 313

Poznan, , Poland

Study Site 315

Poznan, , Poland

Study Site 303

Rzeszów, , Poland

Study Site 310

Warsaw, , Poland

Study Site 301

Warsaw, , Poland

Study Site 312

Warsaw, , Poland

Study Site 302

Wroclaw, , Poland

Countries

United States; Austria; France; Germany; Poland

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-001219-53

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TR11

Identifier Type: -

Identifier Source: org_study_id