Clinical trial NCT03617536: A Study to Evaluate the Safety and Efficacy of CR845 in Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus
Official title: A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Oral CR845 in Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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: 2018-08-06
Enrollment: 269
Sex: ALL
Minimum age (years): 18
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 3 dose levels of oral CR845 compared to placebo in reducing the intensity of itch in chronic kidney disease (CKD) patients with moderate-to-severe pruritus. This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week Treatment Period, and a Follow-up Visit (approximately 7 days after the last dose of study drug).

Detailed description: This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week Treatment Period, and a Follow-up Visit (approximately 7 to 10 days after the last dose of study drug). 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.

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 1:1:1:1 ratio to receive orally once daily either placebo or CR845 tablets at doses of 0.25, 0.5 or 1 mg. Randomization will be stratified according to the patient's renal disease status: moderate CKD; severe CKD non-dialysis; severe CKD on dialysis (ie, 3 categories). A final safety Follow-up Visit will be conducted 7 to 10 days after the last dose of study drug.

Eligibility criteria: Inclusion Criteria:

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

* CKD patients with stage III, IV, or V (ie, moderate renal impairment with estimated glomerular filtration rate (GFR) ≥30 and \<60 mL/min/1.73 m2 or severe renal impairment with estimated GFR \<30 mL/min/1.73 m2).
* For severe CKD patients on hemodialysis, they must be receiving hemodialysis 3 times per week for at least 3 months prior to the start of screening;
* Prior to randomization:

  1. Has completed at least 4 Worst Itching Intensity NRS worksheets from the start of the 7-day Run-in Period;
  2. Has a mean baseline Worst Itching Intensity NRS score ≥5, defined as the average of all non-missing scores reported from the start of the 7-day Run-in Period.

Exclusion Criteria:

A patient will be excluded from the study if any of the following criteria are met:

* Patients not currently on dialysis who are likely to initiate routine dialysis during study participation;
* Scheduled to receive a kidney transplant during the study;
* New or change of treatment received for itch including antihistamines and corticosteroids (oral, intravenous \[IV\], or topical) within 14 days prior to screening;
* Received another investigational drug within 30 days prior to the start of screening or is planning to participate in another clinical study while enrolled in this study;
* Received ultraviolet B treatment within 30 days prior to the start of screening or anticipates receiving such treatment during the study;
* Participated in a previous clinical study with CR845.

Primary outcomes:
measure: Change From Baseline in Weekly Mean of the Daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) Score During Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change From Baseline in Total Skindex-10 Scale Score at the End of Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in 5-D Itch Scale Score at the End of Week 12
timeFrame: Baseline, Week 12
measure: Reduction of Itch Intensity as Assessed by the Proportion of Patients Achieving an Improvement From Baseline ≥3 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score at Week 12
timeFrame: Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cara Therapeutics Study Site
state: Alabama
city: Florence
country: United States
facility: Cara Therapeutics Study Site
state: Alabama
city: Phoenix
country: United States
facility: Cara Therapeutics Study Site
state: Arizona
city: Prescott
country: United States
facility: Cara Therapeutics Study Site
state: Arizona
city: Sun City
country: United States
facility: Cara Therapeutics Study Site
state: Arizona
city: Harrisburg
country: United States
facility: Cara Therapeutics Study Site
state: Arkansas
city: Bakersfield
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Bakersfield
country: United States
facility: Cara Therapeutics Study Site 2
state: California
city: Canyon Country
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Escondido
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Lomita
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Northridge
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Riverside
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Sacramento
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Whittier
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Denver
country: United States
facility: Cara Therapeutics Study Site
state: Colorado
city: Washington
country: United States
facility: Cara Therapeutics Study Site
state: District of Columbia
city: Edgewater
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Hialeah
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Hollywood
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Lake Worth
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Miami
country: United States
facility: Cara Therapeutics Study Site 1
state: Florida
city: Miami
country: United States
facility: Cara Therapeutics Study Site 2
state: Florida
city: Ocala
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Orlando
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Tampa
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Temple Terrace
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Augusta
country: United States
facility: Cara Therapeutics Study Site
state: Georgia
city: Sandy Springs
country: United States
facility: Cara Therapeutics Study Site
state: Georgia
city: Crystal Lake
country: United States
facility: Cara Therapeutics Study Site
state: Illinois
city: Evanston
country: United States
facility: Cara Therapeutics Study Site
state: Illinois
city: Iowa City
country: United States
facility: Cara Therapeutics Study Site
state: Iowa
city: Metairie
country: United States
facility: Cara Therapeutics Study Site
state: Louisiana
city: New Orleans
country: United States
facility: Cara Therapeutics Study Site
state: Louisiana
city: Zachary
country: United States
facility: Cara Therapeutics Study Site
state: Louisiana
city: Baltimore
country: United States
facility: Cara Therapeutics Study Site
state: Maryland
city: Takoma Park
country: United States
facility: Cara Therapeutics Study Site
state: Maryland
city: Flint
country: United States
facility: Cara Therapeutics Study Site
state: Michigan
city: Flint
country: United States
facility: Cara Therapeutics Study Site 2
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: Kansas City
country: United States
facility: Cara Therapeutics Study Site
state: Missouri
city: Brooklyn
country: United States
facility: Cara Therapeutics Study Site
state: New York
city: Mineola
country: United States
facility: Cara Therapeutics Study Site
state: New York
city: Rocky Mount
country: United States
facility: Cara Therapeutics Study Site
state: North Carolina
city: Columbus
country: United States
facility: Cara Therapeutics Study Site
state: Ohio
city: Norman
country: United States
facility: Cara Therapeutics Study Site
state: Oklahoma
city: Camp Hill
country: United States
facility: Cara Therapeutics Study Site
state: Pennsylvania
city: Providence
country: United States
facility: Cara Therapeutics Study Site
state: Rhode Island
city: Warwick
country: United States
facility: Cara Therapeutics Study Site
state: Rhode Island
city: Greenville
country: United States
facility: Cara Therapeutics Study Site
state: South Carolina
city: Rapid City
country: United States
facility: Cara Therapeutics Study Site
state: South Dakota
city: Corsicana
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Gonzales
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: Plano
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: San Antonio
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: San Antonio
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Alexandria
country: United States
facility: Cara Therapeutics Study Site
state: Virginia
Study officials:
affiliation: Cara Therapeutics
name: Frédérique Menzaghi, PhD
role: STUDY_DIRECTOR
References: