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CR845-310302: A Study to Evaluate the Safety and Efficacy of Difelikefalin in Advanced Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus

Primary Purpose

Chronic Kidney Diseases, Pruritus

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Difelikefalin 1 mg Oral Tablet
Placebo Oral Tablet
Sponsored by
Cara Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Kidney Diseases focused on measuring 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

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept 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:

  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.

Sites / Locations

  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
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  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SitesRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
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  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study Site 2Recruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study Site 2Recruiting
  • Cara Therapeutics Study SiteRecruiting
  • Cara Therapeutics Study SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Difelikefalin 1 mg Oral Tablet

Placebo Oral Tablet

Arm Description

Patients receive oral difelikefalin 1 mg once daily

Patients receive oral placebo once daily

Outcomes

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
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.
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.
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.
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.
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".

Full Information

First Posted
April 18, 2022
Last Updated
October 5, 2023
Sponsor
Cara Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05356403
Brief Title
CR845-310302: 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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 26, 2022 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cara Therapeutics, Inc.

4. Oversight

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
Data Monitoring Committee
Yes

5. 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Diseases, Pruritus
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomized, double-blind, placebo controlled study
Masking
ParticipantInvestigator
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.
Allocation
Randomized
Enrollment
400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Difelikefalin 1 mg Oral Tablet
Arm Type
Experimental
Arm Description
Patients receive oral difelikefalin 1 mg once daily
Arm Title
Placebo Oral Tablet
Arm Type
Placebo Comparator
Arm Description
Patients receive oral placebo once daily
Intervention Type
Drug
Intervention Name(s)
Difelikefalin 1 mg Oral Tablet
Other Intervention Name(s)
CR845
Intervention Description
Difelikefalin 1 mg medication taken orally 1 time/day
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
Placebo tablet taken orally 1 time/day
Primary Outcome Measure Information:
Title
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
Description
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".
Time Frame
Week 12 of Treatment Period 1
Secondary Outcome Measure Information:
Title
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.
Description
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".
Time Frame
Week 8 of Treatment Period 1
Title
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.
Description
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".
Time Frame
Week 4 of Treatment Period 1
Title
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.
Description
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".
Time Frame
Week 12 of Treatment Period 1
Title
Efficacy Assessment Phase (Treatment Period 1): Change from baseline in Sleep Quality Questionnaire score at the end of Week 12 of Treatment Period 1.
Description
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".
Time Frame
Week 12 of Treatment Period 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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: 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 the start of run-in.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cara Therapeutics
Phone
203-406-3700
Email
clinicaltrials.gov@caratherapeutics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frédérique Menzaghi, PhD
Organizational Affiliation
Cara Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Cara Therapeutics Study Site
City
Northridge
State/Province
California
ZIP/Postal Code
91324
Country
United States
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33016
Country
United States
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33032
Country
United States
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Weston
State/Province
Florida
ZIP/Postal Code
33331
Country
United States
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Brunswick
State/Province
Georgia
ZIP/Postal Code
31520
Country
United States
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Orangeburg
State/Province
South Carolina
ZIP/Postal Code
29118
Country
United States
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Sugar Land
State/Province
Texas
ZIP/Postal Code
77476
Country
United States
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Adelaide
Country
Australia
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Camperdown
Country
Australia
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Concord
Country
Australia
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Gosford
Country
Australia
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Kogarah
Country
Australia
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Launceston
Country
Australia
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Liverpool
Country
Australia
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Melbourne
Country
Australia
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Saint Albans
Country
Australia
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Westmead
Country
Australia
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Dobrich
Country
Bulgaria
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Montana
Country
Bulgaria
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Plovdiv
Country
Bulgaria
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Sites
City
Stara Zagora
Country
Bulgaria
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Heilbronn
Country
Germany
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Kaiserslautern
Country
Germany
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Baja
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Budapest
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Kistarcsa
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Pécs
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Firenze
Country
Italy
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Roma
Country
Italy
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Daegu
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Goyang-si
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Golub-Dobrzyń
Country
Poland
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Katowice
Country
Poland
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site 2
City
Kraków
Country
Poland
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Kraków
Country
Poland
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Szczecin
Country
Poland
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Wrocław
Country
Poland
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Łódź
Country
Poland
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Bucharest
Country
Romania
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Deva
Country
Romania
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Oradea
Country
Romania
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Badalona
Country
Spain
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site 2
City
Valencia
Country
Spain
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Valencia
Country
Spain
Individual Site Status
Recruiting
Facility Name
Cara Therapeutics Study Site
City
Vitoria
Country
Spain
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

CR845-310302: A Study to Evaluate the Safety and Efficacy of Difelikefalin in Advanced Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus

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