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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05342623
Recruitment Status : Recruiting
First Posted : April 22, 2022
Last Update Posted : May 3, 2023
Sponsor:
Information provided by (Responsible Party):
Cara Therapeutics, Inc.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
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
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
Actual Study Start Date : May 17, 2022
Estimated Primary Completion Date : July 2024
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine


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 Name: CR845

Placebo Comparator: Placebo Oral Tablet
Patients receive oral placebo once daily
Drug: Placebo Oral Tablet
Placebo tablet taken orally 1 time/day




Primary Outcome Measures :
  1. 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".


Secondary Outcome Measures :
  1. 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".

  2. 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".

  3. 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".

  4. 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".



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  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 screening.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05342623


Contacts
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Contact: Cara Therapeutics 203-406-3700 clinicaltrials.gov@caratherapeutics.com

Locations
Show Show 62 study locations
Sponsors and Collaborators
Cara Therapeutics, Inc.
Investigators
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Study Director: Frédérique Menzaghi, PhD Cara Therapeutics
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Responsible Party: Cara Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05342623    
Other Study ID Numbers: CR845-310301
First Posted: April 22, 2022    Key Record Dates
Last Update Posted: May 3, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Cara Therapeutics, Inc.:
difelikefalin
CR845
Pruritus
Chronic Itch
Itch
Itching
uremic pruritus
CKD
CKD-aP
CKD-associated pruritus
Chronic Kidney Disease
Kidney dysfunction
Generalized pruritus
Hemodialysis
Dialysis
ESRD (end stage renal disease)
Kidney failure, chronic
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Pruritus
Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases
Renal Insufficiency
Chronic Disease
Disease Attributes
Pathologic Processes
Skin Diseases
Skin Manifestations