A Study to Evaluate the Safety and Efficacy of Difelikefalin in Advanced Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus and Not on Dialysis

Sponsor

Cara Therapeutics, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05342623

Collaborator

(none)

400

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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 and not on dialysis. 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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Diseases Pruritus	Drug: Difelikefalin 1 mg Oral Tablet Drug: Placebo Oral Tablet	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, double-blind, placebo controlled studyRandomized, 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

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 and Not on Dialysis With an up to 52-Week Long-term Extension

Anticipated Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Difelikefalin 1 mg Oral Tablet Patients receive oral difelikefalin 1 mg once daily	Drug: Difelikefalin 1 mg Oral Tablet Difelikefalin 1 mg medication taken orally 1 time/day Other Names: CR845
Placebo Comparator: Placebo Oral Tablet Patients receive oral placebo once daily	Drug: Placebo Oral Tablet Placebo tablet taken orally 1 time/day

Arm

Intervention/Treatment

Experimental: Difelikefalin 1 mg Oral Tablet

Patients receive oral difelikefalin 1 mg once daily

Drug: Difelikefalin 1 mg Oral Tablet

Difelikefalin 1 mg medication taken orally 1 time/day

Other Names:

CR845

Placebo Comparator: Placebo Oral Tablet

Patients receive oral placebo once daily

Drug: Placebo Oral Tablet

Placebo tablet taken orally 1 time/day

Outcome Measures

Primary Outcome Measures

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 [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".

Secondary Outcome Measures

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. [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. [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. [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. [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".

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Advanced stage 4 and 5 CKD not currently on dialysis
Subject self-reports experiencing daily or near-daily pruritus for at least 6 months prior to screening.
Inadequate response to current or prior topical treatments (including emollients) for pruritus prior to screening.

Prior to randomization on Day 1 of Treatment Period 1:

Has recorded at least 4 WI-NRS scores during the 7-day Run-in Period; and
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 screening.