Clinical trial NCT05356403: 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
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: 2022-05-02
Enrollment: 105
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: Northridge
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Miami Lakes
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Miami Lakes
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Miami
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Weston
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Brunswick
country: United States
facility: Cara Therapeutics Study Site
state: Georgia
city: New York
country: United States
facility: Cara Therapeutics Study Site
state: New York
city: Orangeburg
country: United States
facility: Cara Therapeutics Study Site
state: South Carolina
city: Sugar Land
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Cara Therapeutics Study Site
city: Corrientes
country: Argentina
facility: Cara Therapeutics Study Site
city: Lanús
country: Argentina
facility: Cara Therapeutics Study Site
city: Mar Del Plata
country: Argentina
facility: Cara Therapeutics Study Site
city: San Nicolás
country: Argentina
facility: Cara Therapeutics Study Site
city: Sarandí
country: Argentina
facility: Cara Therapeutics Study Site
city: Adelaide
country: Australia
facility: Cara Therapeutics Study Site
city: Camperdown
country: Australia
facility: Cara Therapeutics Study Site
city: Concord
country: Australia
facility: Cara Therapeutics Study Site
city: Gosford
country: Australia
facility: Cara Therapeutics Study Site
city: Kogarah
country: Australia
facility: Cara Therapeutics Study Site
city: Launceston
country: Australia
facility: Cara Therapeutics Study Site
city: Liverpool
country: Australia
facility: Cara Therapeutics Study Site
city: Melbourne
country: Australia
facility: Cara Therapeutics Study Site
city: Saint Albans
country: Australia
facility: Cara Therapeutics Study Site
city: Westmead
country: Australia
facility: Cara Therapeutics Study Site
city: Belo Horizonte
country: Brazil
facility: Cara Therapeutics Study Site
city: Joinville
country: Brazil
facility: Cara Therapeutics Study Site
city: Salvador
country: Brazil
facility: Cara Therapeutics Study Site
city: São Bernardo Do Campo
country: Brazil
facility: Cara Therapeutics Study Site
city: São José Do Rio Preto
country: Brazil
facility: Cara Therapeutics Study Site
city: São Paulo
country: Brazil
facility: Cara Therapeutics Study Site
city: São Paulo
country: Brazil
facility: Cara Therapeutics Study Site 2
city: São Paulo
country: Brazil
facility: Cara Therapeutics Study Site
city: Dobrich
country: Bulgaria
facility: Cara Therapeutics Study Site
city: Gabrovo
country: Bulgaria
facility: Cara Therapeutics Study Site
city: Montana
country: Bulgaria
facility: Cara Therapeutics Study Site
city: Plovdiv
country: Bulgaria
facility: Cara Therapeutics Study Site
city: Heilbronn
country: Germany
facility: Cara Therapeutics Study Site
city: Kaiserslautern
country: Germany
facility: Cara Therapeutics Study Site
city: Baja
country: Hungary
facility: Cara Therapeutics Study Site
city: Budapest
country: Hungary
facility: Cara Therapeutics Study Site
city: Kistarcsa
country: Hungary
facility: Cara Therapeutics Study Site
city: Pécs
country: Hungary
facility: Cara Therapeutics Study Site
city: Firenze
country: Italy
facility: Cara Therapeutics Study Site
city: Modena
country: Italy
facility: Cara Therapeutics Study Site
city: Pavia
country: Italy
facility: Cara Therapeutics Study Site
city: Roma
country: Italy
facility: Cara Therapeutics Study Site
city: Daegu
country: Korea, Republic of
facility: Cara Therapeutics Study Site
city: Goyang-si
country: Korea, Republic of
facility: Cara Therapeutics Study Site 2
city: Goyang-si
country: Korea, Republic of
facility: Cara Therapeutics Study Site
city: Seoul
country: Korea, Republic of
facility: Cara Therapeutics Study Site
city: Seoul
country: Korea, Republic of
facility: Cara Therapeutics Study Site
city: Aguas Calientes
country: Mexico
facility: Cara Therapeutics Study Site
city: Durango
country: Mexico
facility: Cara Therapeutics Study Site
city: Guadalajara
country: Mexico
facility: Cara Therapeutics Study Site
city: Mérida
country: Mexico
facility: Cara Therapeutics Study Site
city: Golub-Dobrzyń
country: Poland
facility: Cara Therapeutics Study Site
city: Katowice
country: Poland
facility: Cara Therapeutics Study Site
city: Kraków
country: Poland
facility: Cara Therapeutics Study Site 2
city: Kraków
country: Poland
facility: Cara Therapeutics Study Site
city: Szczecin
country: Poland
facility: Cara Therapeutics Study Site
city: Wrocław
country: Poland
facility: Cara Therapeutics Study Site
city: Łódź
country: Poland
facility: Cara Therapeutics Study Site
city: Bucharest
country: Romania
facility: Cara Therapeutics Study Site
city: Oradea
country: Romania
facility: Cara Therapeutics Study Site
city: Timişoara
country: Romania
facility: Cara Therapeutics Study Site
city: Almería
country: Spain
facility: Cara Therapeutics Study Site
city: Badalona
country: Spain
facility: Cara Therapeutics Study Site
city: Barcelona
country: Spain
facility: Cara Therapeutics Study Site
city: Ferrol
country: Spain
facility: Cara Therapeutics Study Site
city: Madrid
country: Spain
facility: Cara Therapeutics Study Site
city: Palma De Mallorca
country: Spain
facility: Cara Therapeutics Study Site
city: Valencia
country: Spain
facility: Cara Therapeutics Study Site 2
city: Valencia
country: Spain
facility: Cara Therapeutics Study Site
city: Vitoria
country: Spain
facility: Cara Therapeutics Study Site
Study officials:
affiliation: Cara Therapeutics
name: Cara Therapeutics, PhD
role: STUDY_DIRECTOR
References: