Prurigo Nodularis MedDRA version: 20.0 Level: LLT Classification code 10037084 Term: Prurigo nodularis System Organ Class: 100000004858
Conditions
Interventions
Product Name: Nalbuphine Extended Release Tablets
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Nalbuphine
CAS Number: 20594-83-6
Sponsors
Trevi Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Individuals diagnosed with PN, defined as the presence of = 20 pruriginous nodules, with predominantly nodular lesions overall. 2. Generalized PN, defined as PN lesions with a nodular component involving 2 distinct anatomical areas: for example, either 2 limbs; or a single limb and some axial portion of the body. Individuals with only axial lesions with 2 distinct anatomical areas of involvement, that have no peripheral nervous system overlap, are also eligible: for example, lesions involving a portion of the cranium and a portion of the trunk of the body. For purposes of this study, the axial portion will be defined as any non-appendicular portion of the body. 3. WINRS score, recorded daily over the 7 contiguous days prior to the baseline visit via electronic diary, must have at least 5 measurements recorded and all individual measurements must be = 6. The arithmetic mean value of the measurements must be = 7. If necessary, the last WINRS value used in the calculation may be recorded on the day of the baseline visit as long as it occurs prior to dosing. 4. Subjects using antidepressant and/or neuroleptic medications must be on a stable dose for a minimum of 8 weeks prior to signing consent and must be willing to remain on their stable dose for the entire duration of the study. 5. Subjects 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) CD4 count > 500 cells/mL; and (c) HIV ribonucleic acid (RNA) 50 years) or surgically sterile (i.e., tubal ligation, hysterectomy, and/or bilateral oophorectomy). Sexually active female subjects of childbearing potential are required to use 1 barrier method (e.g., condom, cervical cap, or diaphragm) of contraception in addition to 1 other method (e.g., intrauterine device in place at least 1 month, stable hormonal contraception for at least 3 months, or Essure procedure, or spermicide). For female subjects using a barrier method plus spermicide, that method must be used for at least 14 days prior to screening. Female subjects who are abstinent may participate in the study, however; they must be counseled on the requirement to use appropriate contraception should they become sexually active. This counseling should occur at each study visit and must be documented in source records. 7. Age 18 years and older at the time of consent, and a life expectancy of at least 18 months. 8. Willing and able to understand and
Exclusion criteria
Exclusion criteria: 1. Pruritus due to localized PN (only 1 body part affected, for example only 1 arm). 2. Active, uncontrolled, pruritic dermatoses in need of treatment (such as atopic dermatitis, or bullous pemphigoid for example) or other dermatologic conditions that in the opinion of the Investigator could confound the ability to assess PN-related itch. 3. Prurigo Nodularis associated with a history of atopic dermatitis is excluded if acute eczematous lesions are present, as characterized by erythematous, active-predominant lichenified plaques with oozing and crusting. 4. Major psychiatric disorder, which in the opinion of the Investigator, could interfere with the assessment of anti-pruritic efficacy and/or safety events during the study or with the ability of the subject to cooperate with study requirements. 5. Serum bilirubin > 2.5 × upper limit of normal range at screening unless explained by a clinical diagnosis of Gilbert's Syndrome. 6. Serum hepatic alanine aminotransferase or aspartate aminotransferase enzymes > 100 U/L at screening. 7. Estimated glomerular filtration rate = 44 mL/min/1.73 m^2 at screening. 8. Significant medical condition or other factors that in the opinion of the Investigator may interfere with the conduct of the study. 9. Subjects who have an active malignancy (either solid tumor or hematologic) are excluded. Subjects who have a past history of malignancy and who have no evidence of active disease, but who continue on therapy to prevent disease recurrence (i.e., tamoxifen for breast cancer, testosterone blockade for prostate cancer, etc.), may be eligible if approved by the Medical Monitor. 10. History of substance abuse which as determined by the Investigator may interfere with the conduct of the study. 11. Known intolerance of or hypersensitivity or allergy to nalbuphine or vehicle components. 12. Pregnant or lactating females. 13. Concurrent enrollment in an ongoing clinical trial or anticipated enrollment in a concurrent clinical trial. Medication-related Exclusions: 14. Known intolerance (gastrointestinal, central nervous system symptoms) or hypersensitivity/drug allergy to opioids. 15. Potential subjects taking monoamine oxidase inhibitors are excluded, as concomitant opiate use may increase the risk for serotonin syndrome. 16. Potential subjects taking cyclosporin A are excluded unless they undergo a 6-week washout prior to beginning the screening period. Washout should occur after signing informed consent, if done for study participation purposes, and prior to electronic diary (e-diary) WINRS collection. WINRS collection should not take place prior to 6 weeks after discontinuation of cyclosporin A. Subjects are prohibited from using cyclosporin during the study. 17. Potential subjects taking biologics (including monoclonal antibodies), which modify the immune system, are excluded unless they undergo a 3-month washout prior to beginning the screening period. Washout should occur after signing informed consent, if done for study participation purposes, and prior to e-diary WINRS collection. 18. Potential subjects who have previously received dupilumab or nemoliz
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • 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 [WINRS]); Secondary Objective: • To evaluate the effect of NAL ER on itch as assessed by the mean change in WINRS • To evaluate the effect of NAL ER on the ItchyQoL total score • To evaluate the effect of NAL ER on Prurigo Nodularis (PN) skin lesions • To evaluate the benefit to subjects of NAL ER using the Patient Benefit Index, pruritus version (PBI-P) • To evaluate the effect of NAL ER on sleep using the PROMIS Sleep Disturbance Short Form 8a • To characterize the safety and tolerability of NAL ER • To assess the pharmacokinetics (PK) of nalbuphine and its metabolites ;Primary end point(s): The primary efficacy endpoint is the difference between the percent “Responders” at Week 14 for the NAL ER treatment arm versus the placebo arm. A “Responder” is defined as a subject with a = 4-point decrease in the 7 day average WINRS from baseline to Week 14.;Timepoint(s) of evaluation of this end point: Week 14 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary efficacy Endpoints: • The mean change in 7-day average WINRS from baseline to Week 14 for the NAL ER treatment arm versus the placebo arm • The change in mean score of the ItchyQoL from baseline to Week 14 for the NAL ER treatment arm versus the placebo arm • Change in Prurigo Activity Score (PAS) as assessed by the percentage of subjects having a 1-category improvement in the percentage of prurigenous lesions with excoriations/crusts (item 5a) from baseline to Week 14 for the NAL ER treatment arm versus the placebo arm Other secondary efficacy endpoints include the following: • Change in PAS as assessed by the percentage of subjects having a 1-category improvement in the percentage of healed lesions (item 5b) from baseline to Week 14 for the NAL ER treatment arm versus the placebo arm • Change in PAS as assessed by the percentage of subjects having a 1-category improvement in the percentage number of lesions (item 2) from baseline to Week 14 for the NAL ER treatment arm versus the placebo arm • Change in Investigator Global Assessment-Prurigo Nodularis (IGA-PN) as assessed by the percentage of subjects having a 1-category improvement in activity • Change in IGA-PN as assessed by the percentage of subjects having a 1-category improvement in stage • The mean change in sleep disturbance (PROMIS Sleep disturbance Short Form 8a) from baseline to Week 14 for the NAL ER treatment arm versus the placebo arm • The mean change in PBI-P from baseline to Week 14 for the NAL ER treatment arm versus the placebo arm Safety: All on-treatment safety data will be assessed descriptively based on the number and rates of adverse events (AEs), Serious AEs (SAEs), clinical laboratory measurements, central cardiac core laboratory read12lead ECG | — |
Countries
Austria, France, Germany, Poland, United States
Contacts
Public ContactVicki Duvall
Trevi Therapeutics, Inc.
Outcome results
None listed