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

Chronic Kidney Diseases Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05342623
• Other study ID #: CR845-310301
• Status: Terminated
• Phase: Phase 3
• Start date: May 17, 2022
• Est. completion date: February 29, 2024

Study information

• Verified date: May 2024
• Source: Cara Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 286
• Est. completion date: February 29, 2024
• Est. primary completion date: February 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Kidney Diseases
• Pruritus
• Renal Insufficiency, Chronic

Intervention

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

Locations

Country	Name	City	State
United States	Cara Therapeutics Study Site	Albany	Georgia
United States	Cara Therapeutics Study Site	Anaheim	California
United States	Cara Therapeutics Study Site	Ardmore	Oklahoma
United States	Cara Therapeutics Study Site	Arvada	Colorado
United States	Cara Therapeutics Study Site	Atlantis	Florida
United States	Cara Therapeutics Study Site	Austin	Texas
United States	Cara Therapeutics Study Site	Bakersfield	California
United States	Cara Therapeutics Study Site	Baton Rouge	Louisiana
United States	Cara Therapeutics Study Site	Bethlehem	Pennsylvania
United States	Cara Therapeutics Study Site	Beverly Hills	California
United States	Cara Therapeutics Study Site	Boston	Massachusetts
United States	Cara Therapeutics Study Site	Bronx	New York
United States	Cara Therapeutics Study Site	Cape Coral	Florida
United States	Cara Therapeutics Study Site	Chattanooga	Tennessee
United States	Cara Therapeutics Study Site	Chula Vista	California
United States	Cara Therapeutics Study Site	Columbus	Ohio
United States	Cara Therapeutics Study Site	Coral Gables	Florida
United States	Cara Therapeutics Study Sites	Corsicana	Texas
United States	Cara Therapeutics Study Site	Denver	Colorado
United States	Cara Therapeutics Study Site	Durham	North Carolina
United States	Cara Therapeutics Study Site	East Point	Georgia
United States	Cara Therapeutics Study Site	East Providence	Rhode Island
United States	Cara Therapeutics Study Site	El Centro	California
United States	Cara Therapeutics Study Site	El Paso	Texas
United States	Cara Therapeutics Study Site	Flint	Michigan
United States	Cara Therapeutics Study Site	Fort Lauderdale	Florida
United States	Cara Therapeutics Study Site	Garden Grove	California
United States	Cara Therapeutics Study Site	Greenville	Texas
United States	Cara Therapeutics Study Site	Hampton	Virginia
United States	Cara Therapeutics Study Site	Hialeah	Florida
United States	Cara Therapeutics Study Site	Houston	Texas
United States	Cara Therapeutics Study Site	Houston	Texas
United States	Cara Therapeutics Study Site 2	Houston	Texas
United States	Cara Therapeutics Study Site	Huntley	Illinois
United States	Cara Therapeutics Study Site	Huntsville	Alabama
United States	Cara Therapeutics Study Site	Jackson	Tennessee
United States	Cara Therapeutics Study Site	Kalamazoo	Michigan
United States	Cara Therapeutics Study Site	Kansas City	Kansas
United States	Cara Therapeutics Study Site	Kansas City	Missouri
United States	Cara Therapeutics Study Site	Knoxville	Tennessee
United States	Cara Therapeutics Study Site	La Mesa	California
United States	Cara Therapeutics Study Site	Las Vegas	Nevada
United States	Cara Therapeutics Study Site	Laurelton	New York
United States	Cara Therapeutics Study Site	Lewisville	Texas
United States	Cara Therapeutics Study Site	Lima	Ohio
United States	Cara Therapeutics Study Site	Louisville	Kentucky
United States	Cara Therapeutics Study Site	McAllen	Texas
United States	Cara Therapeutics Study Site	McKinney	Texas
United States	Cara Therapeutics Study Site	Metairie	Louisiana
United States	Cara Therapeutics Study Site	Miami	Florida
United States	Cara Therapeutics Study Site	Miami	Florida
United States	Cara Therapeutics Study Site	Nampa	Idaho
United States	Cara Therapeutics Study Site	New Haven	Connecticut
United States	Cara Therapeutics Study Site	Northridge	California
United States	Cara Therapeutics Study Site	Ontario	California
United States	Cara Therapeutics Study Site	Orange City	Florida
United States	Cara Therapeutics Study Site	Orlando	Florida
United States	Cara Therapeutics Study Site 2	Orlando	Florida
United States	Cara Therapeutics Study Site	Palos Hills	Illinois
United States	Cara Therapeutics Study Site	Pasadena	Texas
United States	Cara Therapeutics Study Site	Pembroke Pines	Florida
United States	Cara Therapeutics Study Site	Phoenix	Arizona
United States	Cara Therapeutics Study Site	Providence	Rhode Island
United States	Cara Therapeutics Study Site	Riverside	California
United States	Cara Therapeutics Study Site	Riverview	Florida
United States	Cara Therapeutics Study Site	Roseville	Michigan
United States	Cara Therapeutics Study Site	S. Gate	California
United States	Cara Therapeutics Study Site	Saint Clair	Michigan
United States	Cara Therapeutics Study Site	Saint Joseph	Michigan
United States	Cara Therapeutics Study Site	Santa Clara	California
United States	Cara Therapeutics Study Site	Sherman	Texas
United States	Cara Therapeutics Study Site	Shreveport	Louisiana
United States	Cara Therapeutics Study Site	Spartanburg	South Carolina
United States	Cara Therapeutics Study Site	Surprise	Arizona
United States	Cara Therapeutics Study Site	Tampa	Florida
United States	Cara Therapeutics Study Site	Tarzana	California
United States	Cara Therapeutics Study Site	Tupelo	Mississippi
United States	Cara Therapeutics Study Site	Upland	Pennsylvania
United States	Cara Therapeutics Study Site	Vacaville	California
United States	Cara Therapeutics Study Site	Valencia	California
United States	Cara Therapeutics Study Site	Victorville	California
United States	Cara Therapeutics Study Site	West Palm Beach	Florida
United States	Cara Therapeutics Study Site	Zachary	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Cara Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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".	Week 12 of Treatment Period 1
Secondary	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".	Week 8 of Treatment Period 1
Secondary	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".	Week 4 of Treatment Period 1
Secondary	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".	Week 12 of Treatment Period 1
Secondary	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".	Week 12 of Treatment Period 1