PRISM Study-Pruritus Relief Through Itch Scratch Modulation

Prurigo Nodularis Clinical Trial

— PRISM  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03497975
• Other study ID #: TR11
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: August 7, 2018
• Est. completion date: February 24, 2023

Study information

• Verified date: January 2023
• Source: Trevi Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 353
• Est. completion date: February 24, 2023
• Est. primary completion date: May 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Prurigo
• Prurigo Nodularis
• Pruritus

Intervention

Drug:
• Nalbuphine ER Tablets
Active Nalbuphine ER Tablets

Other:
• Matching Placebo Tablets
Matching Tablets with no active substance

Drug:
• Nalbuphine ER Tablets
Open Label Extension

Locations

Country	Name	City	State
Austria	Study Site 401	Graz
Austria	Study Site 402	Linz
France	Study Site 501	Brest
France	Study Site 502	Paris
Germany	Study Site 205	Bad Bentheim
Germany	Study Site 208	Berlin
Germany	Study Site 209	Berlin
Germany	Study Site 216	Berlin
Germany	Study Site 219	Cologne
Germany	Study Site 213	Dresden	Sachsen
Germany	Study Site 221	Düsseldorf
Germany	Study Site 204	Frankfurt	Hessen
Germany	Study Site 215	Hamburg
Germany	Study Site 222	Hamburg
Germany	Study Site 212	Heidelberg
Germany	Study Site 214	Kiel
Germany	Study Site 201	Mainz	Rheinland-Pfalz
Germany	Study Site 220	Muenchen
Germany	Study Site 202	Münster	North Rhine-Westphal
Germany	Study Site 206	Stuttgart
Poland	Study Site 304	Bialystok
Poland	Study Site 306	Katowice
Poland	Study Site 316	Krakow
Poland	Study Site 308	Kraków
Poland	Study Site 309	Lódz
Poland	Study Site 314	Lublin
Poland	Study Site 305	Ostrowiec Swietokrzyski
Poland	Study Site 313	Poznan
Poland	Study Site 315	Poznan
Poland	Study Site 303	Rzeszów
Poland	Study Site 301	Warsaw
Poland	Study Site 310	Warsaw
Poland	Study Site 312	Warsaw
Poland	Study Site 302	Wroclaw
United States	Study Site 143	Ann Arbor	Michigan
United States	Study Site 137	Austin	Texas
United States	Study Site 138	Boca Raton	Florida
United States	Study Site 136	Boston	Massachusetts
United States	Study Site 153	Brighton	Massachusetts
United States	Study Site 107	Charleston	South Carolina
United States	Study Site 147	Charleston	South Carolina
United States	Study Site 140	Chattanooga	Tennessee
United States	Study Site 122	Cincinnati	Ohio
United States	Study Site 120	Cleveland	Ohio
United States	Study Site 121	Fremont	California
United States	Study Site 159	Hackensack	New Jersey
United States	Study Site 144	Henderson	Nevada
United States	Study Site 132	Hershey	Pennsylvania
United States	Study Site 131	Johnston	Rhode Island
United States	Study Site 145	Knoxville	Tennessee
United States	Study Site 157	Laguna Niguel	California
United States	Study Site 146	Las Vegas	Nevada
United States	Study Site 148	Morgantown	West Virginia
United States	Study Site 141	North Hollywood	California
United States	Study Site 158	Orlando	Florida
United States	Study Site 106	Philadelphia	Pennsylvania
United States	Study Site 151	Phoenix	Arizona
United States	Study Site 109	Portsmouth	New Hampshire
United States	Study Site 102	Rockville	Maryland
United States	Study Site 118	Saint Joseph	Missouri
United States	Study Site 130	San Francisco	California
United States	Study Site 108	South Miami	Florida
United States	Study Site 135	Spokane	Washington
United States	Study Site 134	Stony Brook	New York
United States	Study Site 142	Tampa	Florida
United States	Study Site 139	Troy	Michigan
United States	Study Site 128	Washington	District of Columbia
United States	Study Site 103	Webster	Texas
United States	Study Site 150	West Jordan	Utah
United States	Study Site 101	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Trevi Therapeutics

Countries where clinical trial is conducted

United States,  Austria,  France,  Germany,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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