Clinical trial NCT05342623: 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
Overall status: TERMINATED
Phase: PHASE3
Conditions: 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
Lead sponsor: Cara Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-22
Enrollment: 286
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo controlled study
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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
timeFrame: Week 12 of Treatment Period 1
Secondary outcomes:
measure: 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.
timeFrame: Week 8 of Treatment Period 1
measure: 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.
timeFrame: Week 4 of Treatment Period 1
measure: 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.
timeFrame: Week 12 of Treatment Period 1
measure: Efficacy Assessment Phase (Treatment Period 1): Change from baseline in Sleep Quality Questionnaire score at the end of Week 12 of Treatment Period 1.
timeFrame: Week 12 of Treatment Period 1
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Cara Therapeutics Study Site
state: Alabama
city: Phoenix
country: United States
facility: Cara Therapeutics Study Site
state: Arizona
city: Surprise
country: United States
facility: Cara Therapeutics Study Site
state: Arizona
city: Anaheim
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Bakersfield
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Beverly Hills
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Chula Vista
country: United States
facility: Cara Therapeutics Study Site
state: California
city: El Centro
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Garden Grove
country: United States
facility: Cara Therapeutics Study Site
state: California
city: La Mesa
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Northridge
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Ontario
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Riverside
country: United States
facility: Cara Therapeutics Study Site
state: California
city: S. Gate
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Santa Clara
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Tarzana
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Vacaville
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Valencia
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Victorville
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Arvada
country: United States
facility: Cara Therapeutics Study Site
state: Colorado
city: Denver
country: United States
facility: Cara Therapeutics Study Site
state: Colorado
city: New Haven
country: United States
facility: Cara Therapeutics Study Site
state: Connecticut
city: Atlantis
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Cape Coral
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Coral Gables
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Fort Lauderdale
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Hialeah
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Miami
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Miami
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Orange City
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Orlando
country: United States
facility: Cara Therapeutics Study Site 2
state: Florida
city: Orlando
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Pembroke Pines
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Riverview
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Tampa
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: West Palm Beach
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Albany
country: United States
facility: Cara Therapeutics Study Site
state: Georgia
city: East Point
country: United States
facility: Cara Therapeutics Study Site
state: Georgia
city: Nampa
country: United States
facility: Cara Therapeutics Study Site
state: Idaho
city: Huntley
country: United States
facility: Cara Therapeutics Study Site
state: Illinois
city: Palos Hills
country: United States
facility: Cara Therapeutics Study Site
state: Illinois
city: Kansas City
country: United States
facility: Cara Therapeutics Study Site
state: Kansas
city: Louisville
country: United States
facility: Cara Therapeutics Study Site
state: Kentucky
city: Baton Rouge
country: United States
facility: Cara Therapeutics Study Site
state: Louisiana
city: Metairie
country: United States
facility: Cara Therapeutics Study Site
state: Louisiana
city: Shreveport
country: United States
facility: Cara Therapeutics Study Site
state: Louisiana
city: Zachary
country: United States
facility: Cara Therapeutics Study Site
state: Louisiana
city: Boston
country: United States
facility: Cara Therapeutics Study Site
state: Massachusetts
city: Flint
country: United States
facility: Cara Therapeutics Study Site
state: Michigan
city: Kalamazoo
country: United States
facility: Cara Therapeutics Study Site
state: Michigan
city: Roseville
country: United States
facility: Cara Therapeutics Study Site
state: Michigan
city: Saint Clair
country: United States
facility: Cara Therapeutics Study Site
state: Michigan
city: Saint Joseph
country: United States
facility: Cara Therapeutics Study Site
state: Michigan
city: Tupelo
country: United States
facility: Cara Therapeutics Study Site
state: Mississippi
city: Kansas City
country: United States
facility: Cara Therapeutics Study Site
state: Missouri
city: Las Vegas
country: United States
facility: Cara Therapeutics Study Site
state: Nevada
city: Bronx
country: United States
facility: Cara Therapeutics Study Site
state: New York
city: Laurelton
country: United States
facility: Cara Therapeutics Study Site
state: New York
city: Durham
country: United States
facility: Cara Therapeutics Study Site
state: North Carolina
city: Columbus
country: United States
facility: Cara Therapeutics Study Site
state: Ohio
city: Lima
country: United States
facility: Cara Therapeutics Study Site
state: Ohio
city: Ardmore
country: United States
facility: Cara Therapeutics Study Site
state: Oklahoma
city: Bethlehem
country: United States
facility: Cara Therapeutics Study Site
state: Pennsylvania
city: Upland
country: United States
facility: Cara Therapeutics Study Site
state: Pennsylvania
city: East Providence
country: United States
facility: Cara Therapeutics Study Site
state: Rhode Island
city: Providence
country: United States
facility: Cara Therapeutics Study Site
state: Rhode Island
city: Spartanburg
country: United States
facility: Cara Therapeutics Study Site
state: South Carolina
city: Chattanooga
country: United States
facility: Cara Therapeutics Study Site
state: Tennessee
city: Jackson
country: United States
facility: Cara Therapeutics Study Site
state: Tennessee
city: Knoxville
country: United States
facility: Cara Therapeutics Study Site
state: Tennessee
city: Austin
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Corsicana
country: United States
facility: Cara Therapeutics Study Sites
state: Texas
city: El Paso
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Greenville
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Houston
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Houston
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Houston
country: United States
facility: Cara Therapeutics Study Site 2
state: Texas
city: Lewisville
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: McAllen
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: McKinney
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Pasadena
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Sherman
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Hampton
country: United States
facility: Cara Therapeutics Study Site
state: Virginia
Study officials:
affiliation: Cara Therapeutics
name: Cara Therapeutics
role: STUDY_DIRECTOR
References: