A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Intravenous CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus, With a 52-Week Open Label Extension
Overview
- Phase
- Phase 3
- Intervention
- CR845 0.5 mcg/kg
- Conditions
- Uremic Pruritus
- Sponsor
- Cara Therapeutics, Inc.
- Enrollment
- 378
- Locations
- 4
- Primary Endpoint
- Reduction of Itch Intensity as Assessed by the Percentage of Patients Achieving an Improvement From Baseline ≥3 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) Score at Week 12
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of intravenous (IV) CR845 at a dose of 0.5 mcg/kg administered after each dialysis session. The study includes a 12-week Double-blind Phase and a 52-week Open-label Extension Phase.
Detailed Description
Double-blind Phase The Double-blind Phase of the study will consist of a Screening Visit, a 7-day Run-in Period, a 12 week Double-blind Treatment Period, and a 2-week Discontinuation Period. Informed consent will be obtained prior to performing any study-specific procedures. The Screening Visit will occur within 7 to 28 days prior to randomization to assess eligibility. Open-label Extension Phase Patients who received at least 30 doses of study drug (either active or placebo) during the 12-week Double-blind Treatment Period and continue to meet other eligibility criteria will have the option to receive open label CR845 for an additional 52 weeks. The Open-label Extension Phase will be comprised of the Open-label Treatment Period and the Follow-up Period. The last dose of open-label study drug will be administered at the last dialysis visit on Week 52, or Early Termination. A final safety Follow up Visit will be conducted 7-10 days after the End of Treatment/Early Termination Visit.
Investigators
Eligibility Criteria
Inclusion Criteria
- •To be eligible for inclusion into the Double-blind Phase of the study, a patient must meet the following criteria:
- •Has end-stage renal disease (ESRD) and has been on hemodialysis 3 times per week for at least 3 months prior to the start of screening;
- •Has at least 2 single-pool Kt/V measurements ≥1.2, or at least 2 urea reduction ratio measurements ≥65%, or 1 single pool Kt/V measurement ≥1.2 and 1 urea reduction ratio measurement ≥65% on different dialysis days during the 3 months period prior to screening;
- •Prior to randomization:
- •Has completed Worst Itching Intensity NRS worksheets up to 8 days prior to 1st dose;
- •Has a mean baseline Worst Itching Intensity NRS indicative of moderate to severe uremic pruritus.
- •To be eligible for inclusion into the Open-label Extension Phase of the study, each patient will have to fulfill the additional key following criteria at the time of entry into the Open-label Extension Phase:
- •Has received at least 30 doses of the planned 36 doses of study drug during the Double-blind Phase of this study;
- •Continues to meet inclusion criteria.
Exclusion Criteria
- •A patient will be excluded from the Double-blind Phase of the study if any of the following criteria are met:
- •Known noncompliance with dialysis treatment that in the opinion of the investigator would impede completion or validity of the study;
- •Scheduled to receive a kidney transplant during the study;
- •New or change of treatment received for itch including antihistamines and corticosteroids (oral, IV, or topical) within 14 days prior to screening;
- •Received another investigational drug within 30 days prior to the start of screening or is planning to participate in another clinical study while enrolled in this study;
- •Has pruritus only during the dialysis session (by patient report);
- •Is receiving ongoing ultraviolet B and anticipates receiving such treatment during the study;
- •Participated in a previous clinical study with CR
- •A patient will be excluded from the Open-label Extension Phase of the study if any of the additional key following criteria are met at the time of entry into the Open-label Extension Phase:
- •Completed the Double-blind Phase of this study but exhibited adverse events during the course of the Treatment Period that may preclude continued exposure to the study drug;
Arms & Interventions
CR845 0.5mcg/kg
IV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)
Intervention: CR845 0.5 mcg/kg
Placebo
IV Placebo administered after each dialysis session (3 times/week)
Intervention: Placebo
Outcomes
Primary Outcomes
Reduction of Itch Intensity as Assessed by the Percentage of Patients Achieving an Improvement From Baseline ≥3 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) Score at Week 12
Time Frame: Week 12
Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable". LS means estimated percent, odds ratio and P value used a logistic regression model.
Secondary Outcomes
- Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in 5-D Itch Scale Score at the End of Week 12(Baseline, Week 12)
- Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in Total Skindex-10 Scale Score at the End of Week 12(Baseline, Week 12)
- Reduction of Itch Intensity as Assessed by the Percentage of Patients Achieving an Improvement From Baseline ≥4 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score at Week 12(Week 12)