CR845-310302: 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: NCT05356403
• Other study ID #: CR845-310302
• Status: Terminated
• Phase: Phase 3
• Start date: August 26, 2022
• Est. completion date: February 26, 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: 105
• Est. completion date: February 26, 2024
• Est. primary completion date: February 26, 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
Argentina	Cara Therapeutics Study Site	Ciudad Autonoma de Buenos Aire
Argentina	Cara Therapeutics Study Site	Corrientes
Argentina	Cara Therapeutics Study Site	Lanús
Argentina	Cara Therapeutics Study Site	Mar Del Plata
Argentina	Cara Therapeutics Study Site	San Nicolás
Argentina	Cara Therapeutics Study Site	Sarandí
Australia	Cara Therapeutics Study Site	Adelaide
Australia	Cara Therapeutics Study Site	Camperdown
Australia	Cara Therapeutics Study Site	Concord
Australia	Cara Therapeutics Study Site	Gosford
Australia	Cara Therapeutics Study Site	Kogarah
Australia	Cara Therapeutics Study Site	Launceston
Australia	Cara Therapeutics Study Site	Liverpool
Australia	Cara Therapeutics Study Site	Melbourne
Australia	Cara Therapeutics Study Site	Saint Albans
Australia	Cara Therapeutics Study Site	Westmead
Brazil	Cara Therapeutics Study Site	Belo Horizonte
Brazil	Cara Therapeutics Study Site	Joinville
Brazil	Cara Therapeutics Study Site	Salvador
Brazil	Cara Therapeutics Study Site	São Bernardo Do Campo
Brazil	Cara Therapeutics Study Site	São José Do Rio Preto
Brazil	Cara Therapeutics Study Site	São Paulo
Brazil	Cara Therapeutics Study Site	São Paulo
Brazil	Cara Therapeutics Study Site 2	São Paulo
Bulgaria	Cara Therapeutics Study Site	Dobrich
Bulgaria	Cara Therapeutics Study Site	Gabrovo
Bulgaria	Cara Therapeutics Study Site	Montana
Bulgaria	Cara Therapeutics Study Site	Plovdiv
Germany	Cara Therapeutics Study Site	Heilbronn
Germany	Cara Therapeutics Study Site	Kaiserslautern
Hungary	Cara Therapeutics Study Site	Baja
Hungary	Cara Therapeutics Study Site	Budapest
Hungary	Cara Therapeutics Study Site	Kistarcsa
Hungary	Cara Therapeutics Study Site	Pécs
Italy	Cara Therapeutics Study Site	Firenze
Italy	Cara Therapeutics Study Site	Modena
Italy	Cara Therapeutics Study Site	Pavia
Italy	Cara Therapeutics Study Site	Roma
Korea, Republic of	Cara Therapeutics Study Site	Daegu
Korea, Republic of	Cara Therapeutics Study Site	Goyang-si
Korea, Republic of	Cara Therapeutics Study Site 2	Goyang-si
Korea, Republic of	Cara Therapeutics Study Site	Seoul
Korea, Republic of	Cara Therapeutics Study Site	Seoul
Mexico	Cara Therapeutics Study Site	Aguas Calientes
Mexico	Cara Therapeutics Study Site	Durango
Mexico	Cara Therapeutics Study Site	Guadalajara
Mexico	Cara Therapeutics Study Site	Mérida
Poland	Cara Therapeutics Study Site	Golub-Dobrzyn
Poland	Cara Therapeutics Study Site	Katowice
Poland	Cara Therapeutics Study Site	Kraków
Poland	Cara Therapeutics Study Site 2	Kraków
Poland	Cara Therapeutics Study Site	Lódz
Poland	Cara Therapeutics Study Site	Szczecin
Poland	Cara Therapeutics Study Site	Wroclaw
Romania	Cara Therapeutics Study Site	Bucharest
Romania	Cara Therapeutics Study Site	Oradea
Romania	Cara Therapeutics Study Site	Timisoara
Spain	Cara Therapeutics Study Site	Almería
Spain	Cara Therapeutics Study Site	Badalona
Spain	Cara Therapeutics Study Site	Barcelona
Spain	Cara Therapeutics Study Site	Ferrol
Spain	Cara Therapeutics Study Site	Madrid
Spain	Cara Therapeutics Study Site	Palma De Mallorca
Spain	Cara Therapeutics Study Site	Valencia
Spain	Cara Therapeutics Study Site 2	Valencia
Spain	Cara Therapeutics Study Site	Vitoria
United States	Cara Therapeutics Study Site	Brunswick	Georgia
United States	Cara Therapeutics Study Site	Miami	Florida
United States	Cara Therapeutics Study Site	Miami Lakes	Florida
United States	Cara Therapeutics Study Site	Miami Lakes	Florida
United States	Cara Therapeutics Study Site	New York	New York
United States	Cara Therapeutics Study Site	Northridge	California
United States	Cara Therapeutics Study Site	Orangeburg	South Carolina
United States	Cara Therapeutics Study Site	Sugar Land	Texas
United States	Cara Therapeutics Study Site	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Cara Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Bulgaria,  Germany,  Hungary,  Italy,  Korea, Republic of,  Mexico,  Poland,  Romania,  Spain, 

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