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
Other descriptive name: NALBUPHINE
Concentration
Sponsors
Trevi Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Individuals diagnosed with generalized PN, defined as the presence of = 10 pruriginous nodules, involving at least 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 but involving 2 distinct anatomical areas 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. 2. If there is any history of a primary pruritic skin condition other than PN, that condition must have been inactive for at least 6 months prior to screening. 3. Subjects 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 patient 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. 4. Any identified systemic, non-dermatologic disease that could be a potential cause of concomitant pruritus (e.g., thryroid 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. 5. WI-NRS score, recorded daily over the 7 contiguous days prior to and including the day of 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 as confirmed by the Trialogics Eligibility Check report immediately prior to randomization. The last WI-NRS value used in the calculation should be recorded on the day of the baseline visit and prior to dosing. 6. Subjects using antidepressants must be on a stable dose for a minimum of 4 weeks prior to screening and must be willing to remain on their stable dose for the entire duration of the study. 7. 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 steri
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). 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. History of a major psychiatric disorder such as bipolar disorder or schizophrenia is excluded. Subjects with a history of isolated major depression > 3 years previously may be eligible for enrollment if they have access to appropriate psychiatric care. An ‘isolated major depression’ is defined as a single event of depression that includes recurrent thoughts of death, recurrent suicidal ideation with or without a specific plan, or any history of a suicide attempt. Enrollment must be approved by the Medical Monitor. Subjects with general depression who are considered stable may be enrolled. 5. Serum bilirubin > 1.5 × 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, occupational restrictions, and/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 (ie, tamoxifen for breast cancer, testosterone blockade for prostate cancer, etc.), may be eligible if approved by the Medical Monitor. 10. History of active substance abuse within the past 3 years. 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 (other than safety follow-up of a COVID-19 vaccination trial, see protocol for further information). 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. Subjects are prohibited from using cyclosporin during the study. 17. Potential subjects taking non-insulin biologics (including monoclonal antibodies), which modify the immune system, are excluded unless they undergo a 3-month washout. 18. Prior exclusion criterion 18 is not applicable to subjects enrolling in Protocol V6 and later. 19. Exposure to any investigational medication, including placebo requires a 4-week washout (3 months for noninsulin biologics [e.g., monoclonal antibodies]). 20. Potential subjects receiving UV-therapy (PUVA, UVA, UVB, Excimer) requires a 4-week washout. Subjects are prohibited from using UV-therapy for the duration of the study. 21. Potential subjects who are taking opiates require a 14 –day washout. Subjects are prohibited from using opioids, including naltrexone, for
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 [WI-NRS]);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 WI-NRS from baseline to Week 14.;Secondary Objective: Key secondary objectives are as follows: • To evaluate the effect of NAL ER on itch-related quality of life as assessed by the ItchyQoLTM total score • To evaluate the effect of NAL ER on Prurigo Nodularis (PN) skin lesions as assessed by the Prurigo Activity Score (PAS) Question 5a • To evaluate the effect of NAL ER on sleep as assessed by the PROMIS Sleep Disturbance Short Form 8a Other secondary objectives are as follows: • To evaluate the effect of NAL ER on itch as assessed by the mean change in WI-NRS • To evaluate the benefit to subjects of NAL ER using the Patient Benefit Index, pruritus version (PBI-P) • To characterize the safety and tolerability of NAL ER • To assess the pharmacokinetics (PK) of nalbuphine and its metabolites;Timepoint(s) of evaluation of this end point: Week 14 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Key secondary efficacy endpoints: Week 14;Secondary end point(s): Key secondary efficacy Endpoints: • The mean change in ItchyQoL 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 of prurigenous lesions with excoriations/crusts (item 5a) from baseline to Week 14 for the NAL ER treatment arm versus the placebo arm • 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 Other secondary efficacy endpoints include the following: • The mean change in 7-day average WI-NRS 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 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 proportion of subjects having a PBI-P score of >=1 at 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, vital signs, and physical examinations. Subjects will also complete the Subjective Opiate Withdrawal Scale (SOWS) on a daily basis for | — |
Countries
Austria, France, Germany, Poland, United States
Contacts
Public ContactPaula Buckley
Trevi Therapeutics, Inc.
Outcome results
None listed