A Study to Evaluate the Safety and Efficacy of Difelikefalin in Advanced Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus

• ClinicalTrials.gov Identifier: NCT05342623
• Recruitment Status: Terminated
• First Posted: April 22, 2022
• Last Update Posted: May 7, 2024
• Sponsor: Cara Therapeutics, Inc.
• Information provided by (Responsible Party): Cara Therapeutics, Inc.

Tracking Information

• First Submitted Date: April 18, 2022
• First Posted Date: April 22, 2022
• Last Update Posted Date: May 7, 2024
• Actual Study Start Date: May 17, 2022
• Actual Primary Completion Date: February 29, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 18, 2022)

Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects achieving at least a 4-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS score at Week 12 of Treatment Period 1 [ Time Frame: Week 12 of Treatment Period 1 ]

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".

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 18, 2022)

• Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects achieving at least a 4-point improvement from baseline with respect to the weekly mean of the WI-NRS at Week 8 of Treatment Period 1. [ Time Frame: Week 8 of Treatment Period 1 ]
  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".
• Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects achieving at least a 4-point improvement from baseline with respect to the weekly mean of the WI-NRS at Week 4 of Treatment Period 1. [ Time Frame: Week 4 of Treatment Period 1 ]
  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".
• Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects who are "complete itch responders" defined as subjects with ≥ 70% of the non-missing 24-hour WI-NRS scores equal to 0 or 1 at Week 12 of Treatment Period 1. [ Time Frame: Week 12 of Treatment Period 1 ]
  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".
• Efficacy Assessment Phase (Treatment Period 1): Change from baseline in Sleep Quality Questionnaire score at the end of Week 12 of Treatment Period 1. [ Time Frame: Week 12 of Treatment Period 1 ]
  Sleep Quality will be measured using an NRS used to indicate how much itch has interfered with sleep during the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "did not interfere" and "10" represents "completely interfered".

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety and Efficacy of Difelikefalin in Advanced Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled 12-Week Study to Evaluate the Safety and Efficacy of Oral Difelikefalin in Advanced Chronic Kidney Disease Subjects With Moderate-to-Severe Pruritus With an up to 52-Week Long-term Extension
• Brief Summary: This is a multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of oral difelikefalin administered as a 1 mg tablet once daily compared to placebo in reducing the intensity of itch in advanced chronic kidney disease (CKD) patients with moderate-to-severe pruritus. This study is comprised of an Efficacy Assessment Phase and a Long-term Extension Phase. The Efficacy Assessment Phase includes a double-blind 12-week Treatment Period (Treatment Period 1), and the Long-term Extension Phase includes a double-blind Treatment Period (Treatment Period 2) of up to 52 weeks.

Detailed Description

This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week double-blind Efficacy Assessment Phase (Treatment Period 1), a double-blind Long-term Extension Phase (Treatment Period 2) of up to 52 weeks, and a Follow-up Visit (7 to 10 days after the End of Treatment (EOT)/Early Termination (ET) Visit).

If patients continue to meet all inclusion and no exclusion criteria at the end of the 7-day Run-in Period, they will be randomized in a 1:1 ratio to receive once daily oral difelikefalin tablets at a dose of 1 mg or placebo for 12 weeks. Subjects will be stratified according to their use or nonuse of medications to treat pruritus prior to randomization as well as the presence or absence of specific medical conditions. During the Long-term Extension Phase, patients will be re-randomized on Day 1 of Treatment Period 2 to receive either oral difelikefalin 1 mg or placebo, once daily for up to an additional 52 weeks. A final safety Follow-up Visit will be conducted 7 to 10 days after the EOT/ET.

Informed consent will be obtained prior to performing any study-specific procedures. Screening will occur within 7 to 28 days prior to randomization to assess eligibility.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized, double-blind, placebo controlled study

Masking: Double (Participant, Investigator)
Masking Description:

Difelikefalin and placebo will be provided as enteric-coated tablets. All tablets are white in color with no markings and are identical in appearance. Difelikefalin tablets will be provided at doses of 1 mg.

Primary Purpose: Treatment

Condition

• Chronic Kidney Diseases
• Pruritus

Intervention

• Drug: Difelikefalin 1 mg Oral Tablet
  Difelikefalin 1 mg medication taken orally 1 time/day
  Other Name: CR845
• Drug: Placebo Oral Tablet
  Placebo tablet taken orally 1 time/day

Study Arms

• Experimental: Difelikefalin 1 mg Oral Tablet
  Patients receive oral difelikefalin 1 mg once daily
  Intervention: Drug: Difelikefalin 1 mg Oral Tablet
• Placebo Comparator: Placebo Oral Tablet
  Patients receive oral placebo once daily
  Intervention: Drug: Placebo Oral Tablet

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 6, 2024): 286
• Original Estimated Enrollment (submitted: April 18, 2022): 400
• Actual Study Completion Date: February 29, 2024
• Actual Primary Completion Date: February 29, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

To be eligible for inclusion into the study, a patient must meet the following criteria:

• Advanced stage 4 and 5 CKD and end stage renal disease on hemodialysis
• Subject self-reports experiencing at least near-daily (eg, most days of a week) pruritus for at least 6 months prior to screening.
• Inadequate response to current or prior treatments (including emollients/moisturizers, topical medications, or systemic treatments) for pruritus prior to screening.

Prior to randomization on Day 1 of Treatment Period 1:

1. Has recorded at least 4 WI-NRS scores during the 7-day Run-in Period; and
2. Has a mean baseline WI-NRS score ≥ 5, defined as the average of all non-missing scores reported during the 7-day Run-in Period.

Exclusion Criteria:

A patient will be excluded from the study if any of the following criteria are met:

• Scheduled to receive a renal replacement therapy (dialysis or kidney transplant) during the study.
• Has a concomitant disease, significant medical condition or physical/laboratory/ECG/vital signs abnormality that, in the opinion of the investigator, puts the subject at undue risk or interferes with interpretation of study results, impedes completion of the study procedures, or compromises the validity of the study measurements.
• New or change of treatment received for itch, including antihistamines and corticosteroids (oral, intravenous, or topical), within 14 days prior to the start of run-in.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05342623
• Other Study ID Numbers: CR845-310301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Cara Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Cara Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Cara Therapeutics; Cara Therapeutics

• PRS Account: Cara Therapeutics, Inc.
• Verification Date: May 2024