A Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (KALM-1)

Phase 3

Completed

• Conditions: Uremic Pruritus
• Interventions: Drug: Placebo; Drug: CR845 0.5 mcg/kg

• Registration Number: NCT03422653
• Lead Sponsor: Cara Therapeutics, Inc.

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.

Study Timeline

• Study First Submitted: 2018-01-25
• Study First Submitted QC: 2018-01-30
• Study First Posted: 2018-02-06
• Study Start: 2018-02-20
• Primary Completion: 2019-04-06
• Study Completion: 2020-03-26
• Disposition First Submitted: 2020-07-14
• Results First Submitted: 2021-09-21
• Status Verified: 2022-03
• Results First Submitted QC: 2022-03-29
• Disposition First Submitted QC: 2022-03-29
• Last Update Submitted: 2022-03-29
• Results First Posted: 2022-04-26
• Disposition First Posted: 2022-04-26
• Last Update Posted: 2022-04-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 378

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.

Key

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 CR845.

• 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;
  • Was noncompliant with protocol procedures during the Double-blind Phase of this study which is indicative of an inability to follow protocol procedures.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	IV Placebo administered after each dialysis session (3 times/week)
CR845 0.5mcg/kg	CR845 0.5 mcg/kg	IV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)

Primary Outcome Measures

Name	Time	Method
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	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 Outcome Measures

Name	Time	Method
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	The 5-D Itch Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past 2 weeks. The questions cover five dimensions of itch including the degree, duration of itch/day, direction (improvement/worsening), disability (impact on activities such as work), and body distribution of itch. The 5-D Itch Scale has 5 questions; the total 5-D Itch Scale score ranges from 5 to 25, with higher scores indicating worse responses.
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	The Skindex-10 Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past week. The questions cover 3 domains: disease, mood/emotional distress, and social functioning domain. The Skindex-10 has 10 questions; the total Skindex-10 score ranges from 0 to 60. A lower total score represents better quality of life.
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	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.

Trial Locations

Locations (4)

Cara Therapeutics Study Site 2; 🇺🇸 Beverly Hills, California, United States

Cara Therapeutics Study Site; 🇺🇸 Wauwatosa, Wisconsin, United States

Cara Therapeutics; 🇺🇸 La Mesa, California, United States

Cara Therapeutics Study Site 1; 🇺🇸 Coral Springs, Florida, United States