Clinical trial NCT03497975: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Prurigo Nodularis
Lead sponsor: Trevi Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-04-13
Enrollment: 353
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized, double-blinded, placebo-controlled, 2-arm study with an open label extension period following double-blind treatment.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Comparison of percentage of responders by arm
timeFrame: 14 weeks
Secondary outcomes:
measure: Change from baseline for itch-related quality of life: ItchyQoL total score
timeFrame: 14 weeks
measure: Change from baseline for Prurigo Nodularis skin lesions
timeFrame: 14 weeks
measure: Change from baseline for sleep disturbance
timeFrame: at week 14
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Study Site 151
state: Arizona
city: Fremont
country: United States
facility: Study Site 121
state: California
city: Laguna Niguel
country: United States
facility: Study Site 157
state: California
city: North Hollywood
country: United States
facility: Study Site 141
state: California
city: San Francisco
country: United States
facility: Study Site 130
state: California
city: Washington
country: United States
facility: Study Site 128
state: District of Columbia
city: Boca Raton
country: United States
facility: Study Site 138
state: Florida
city: Orlando
country: United States
facility: Study Site 158
state: Florida
city: South Miami
country: United States
facility: Study Site 108
state: Florida
city: Tampa
country: United States
facility: Study Site 142
state: Florida
city: Rockville
country: United States
facility: Study Site 102
state: Maryland
city: Boston
country: United States
facility: Study Site 136
state: Massachusetts
city: Brighton
country: United States
facility: Study Site 153
state: Massachusetts
city: Ann Arbor
country: United States
facility: Study Site 143
state: Michigan
city: Troy
country: United States
facility: Study Site 139
state: Michigan
city: Saint Joseph
country: United States
facility: Study Site 118
state: Missouri
city: Henderson
country: United States
facility: Study Site 144
state: Nevada
city: Las Vegas
country: United States
facility: Study Site 146
state: Nevada
city: Portsmouth
country: United States
facility: Study Site 109
state: New Hampshire
city: Hackensack
country: United States
facility: Study Site 159
state: New Jersey
city: Stony Brook
country: United States
facility: Study Site 134
state: New York
city: Wilmington
country: United States
facility: Study Site 101
state: North Carolina
city: Cincinnati
country: United States
facility: Study Site 122
state: Ohio
city: Cleveland
country: United States
facility: Study Site 120
state: Ohio
city: Hershey
country: United States
facility: Study Site 132
state: Pennsylvania
city: Philadelphia
country: United States
facility: Study Site 106
state: Pennsylvania
city: Johnston
country: United States
facility: Study Site 131
state: Rhode Island
city: Charleston
country: United States
facility: Study Site 147
state: South Carolina
city: Charleston
country: United States
facility: Study Site 107
state: South Carolina
city: Chattanooga
country: United States
facility: Study Site 140
state: Tennessee
city: Knoxville
country: United States
facility: Study Site 145
state: Tennessee
city: Austin
country: United States
facility: Study Site 137
state: Texas
city: Webster
country: United States
facility: Study Site 103
state: Texas
city: West Jordan
country: United States
facility: Study Site 150
state: Utah
city: Spokane
country: United States
facility: Study Site 135
state: Washington
city: Morgantown
country: United States
facility: Study Site 148
state: West Virginia
city: Graz
country: Austria
facility: Study Site 401
city: Linz
country: Austria
facility: Study Site 402
city: Brest
country: France
facility: Study Site 501
city: Paris
country: France
facility: Study Site 502
city: Frankfurt
country: Germany
facility: Study Site 204
state: Hessen
city: Münster
country: Germany
facility: Study Site 202
state: North Rhine-Westphal
city: Mainz
country: Germany
facility: Study Site 201
state: Rheinland-Pfalz
city: Dresden
country: Germany
facility: Study Site 213
state: Sachsen
city: Bad Bentheim
country: Germany
facility: Study Site 205
city: Berlin
country: Germany
facility: Study Site 216
city: Berlin
country: Germany
facility: Study Site 209
city: Berlin
country: Germany
facility: Study Site 208
city: Cologne
country: Germany
facility: Study Site 219
city: Düsseldorf
country: Germany
facility: Study Site 221
city: Hamburg
country: Germany
facility: Study Site 215
city: Hamburg
country: Germany
facility: Study Site 222
city: Heidelberg
country: Germany
facility: Study Site 212
city: Kiel
country: Germany
facility: Study Site 214
city: Muenchen
country: Germany
facility: Study Site 220
city: Stuttgart
country: Germany
facility: Study Site 206
city: Białystok
country: Poland
facility: Study Site 304
city: Katowice
country: Poland
facility: Study Site 306
city: Krakow
country: Poland
facility: Study Site 316
city: Kraków
country: Poland
facility: Study Site 308
city: Lublin
country: Poland
facility: Study Site 314
city: Ostrowiec Świętokrzyski
country: Poland
facility: Study Site 305
city: Poznań
country: Poland
facility: Study Site 313
city: Poznań
country: Poland
facility: Study Site 315
city: Rzeszów
country: Poland
facility: Study Site 303
city: Warsaw
country: Poland
facility: Study Site 310
city: Warsaw
country: Poland
facility: Study Site 301
city: Warsaw
country: Poland
facility: Study Site 312
city: Wrocław
country: Poland
facility: Study Site 302
city: Łódź
country: Poland
facility: Study Site 309
Study officials:
affiliation: Trevi Therapeutics
name: David Clark, MD
role: STUDY_DIRECTOR
References: