CR845-310302: A Study to Evaluate the Safety and Efficacy of Difelikefalin in Advanced Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus

NCT05356403 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: CR845-310302
• Study Type: interventional
• Target: 105
• Locations: 13 countries
• Sites: 75

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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.

  Week 8 of Treatment Period 1

• 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.

  Week 4 of Treatment Period 1

• 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.

  Week 12 of Treatment Period 1

• Efficacy Assessment Phase (Treatment Period 1): Change from baseline in Sleep Quality Questionnaire score at the end of Week 12 of Treatment Period 1.

  Week 12 of Treatment Period 1

Study Arms (2)

Difelikefalin 1 mg Oral Tablet

EXPERIMENTAL

Patients receive oral difelikefalin 1 mg once daily

Drug: Difelikefalin 1 mg Oral Tablet

Placebo Oral Tablet

PLACEBO COMPARATOR

Patients receive oral placebo once daily

Drug: Placebo Oral Tablet

Interventions

Difelikefalin 1 mg Oral Tablet DRUG

Difelikefalin 1 mg medication taken orally 1 time/day

Also known as: CR845

Difelikefalin 1 mg Oral Tablet

Placebo Oral Tablet DRUG

Placebo tablet taken orally 1 time/day

Placebo Oral Tablet

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Has recorded at least 4 WI-NRS scores during the 7-day Run-in Period; and
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cara Therapeutics, Inc.: lead

Study Sites (75)

Cara Therapeutics Study Site

Northridge, California, 91324, United States

Location

Cara Therapeutics Study Site

Miami, Florida, 33032, United States

Location

Cara Therapeutics Study Site

Miami Lakes, Florida, 33014, United States

Location

Cara Therapeutics Study Site

Miami Lakes, Florida, 33016, United States

Location

Cara Therapeutics Study Site

Weston, Florida, 33331, United States

Location

Cara Therapeutics Study Site

Brunswick, Georgia, 31520, United States

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Cara Therapeutics Study Site

New York, New York, 10016, United States

Location

Cara Therapeutics Study Site

Orangeburg, South Carolina, 29118, United States

Location

Cara Therapeutics Study Site

Sugar Land, Texas, 77476, United States

Location

Cara Therapeutics Study Site

Ciudad Autonoma de Buenos Aire, C1425DES, Argentina

Location

Cara Therapeutics Study Site

Corrientes, W3400AMZ, Argentina

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Cara Therapeutics Study Site

Lanús, B1824KAJ, Argentina

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Cara Therapeutics Study Site

Mar del Plata, Argentina

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Cara Therapeutics Study Site

San Nicolás, 2900, Argentina

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Cara Therapeutics Study Site

Sarandí, 1872, Argentina

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Cara Therapeutics Study Site

Adelaide, Australia

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Cara Therapeutics Study Site

Camperdown, Australia

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Cara Therapeutics Study Site

Concord, Australia

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Cara Therapeutics Study Site

Gosford, Australia

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Cara Therapeutics Study Site

Kogarah, Australia

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Cara Therapeutics Study Site

Launceston, Australia

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Cara Therapeutics Study Site

Liverpool, Australia

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Cara Therapeutics Study Site

Melbourne, Australia

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Cara Therapeutics Study Site

Saint Albans, Australia

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Cara Therapeutics Study Site

Westmead, Australia

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Cara Therapeutics Study Site

Belo Horizonte, Brazil

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Cara Therapeutics Study Site

Joinville, 89227-680, Brazil

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Cara Therapeutics Study Site

Salvador, Brazil

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Cara Therapeutics Study Site

São Bernardo do Campo, Brazil

Location

Cara Therapeutics Study Site

São José do Rio Preto, Brazil

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Cara Therapeutics Study Site

São Paulo, 09090-790, Brazil

Location

Cara Therapeutics Study Site 2

São Paulo, Brazil

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Cara Therapeutics Study Site

São Paulo, Brazil

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Cara Therapeutics Study Site

Dobrich, Bulgaria

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Cara Therapeutics Study Site

Gabrovo, Bulgaria

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Cara Therapeutics Study Site

Montana, Bulgaria

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Cara Therapeutics Study Site

Plovdiv, Bulgaria

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Cara Therapeutics Study Site

Heilbronn, Germany

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Cara Therapeutics Study Site

Kaiserslautern, Germany

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Cara Therapeutics Study Site

Baja, Hungary

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Cara Therapeutics Study Site

Budapest, Hungary

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Cara Therapeutics Study Site

Kistarcsa, Hungary

Location

Cara Therapeutics Study Site

Pécs, Hungary

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Cara Therapeutics Study Site

Florence, Italy

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Cara Therapeutics Study Site

Modena, 41124, Italy

Location

Cara Therapeutics Study Site

Pavia, 27100, Italy

Location

Cara Therapeutics Study Site

Roma, Italy

Location

Cara Therapeutics Study Site

Aguas Calientes, Mexico

Location

Cara Therapeutics Study Site

Durango, Mexico

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Cara Therapeutics Study Site

Guadalajara, Mexico

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Cara Therapeutics Study Site

Mérida, Mexico

Location

Cara Therapeutics Study Site

Golub-Dobrzyń, Poland

Location

Cara Therapeutics Study Site

Katowice, Poland

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Cara Therapeutics Study Site 2

Krakow, Poland

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Cara Therapeutics Study Site

Krakow, Poland

Location

Cara Therapeutics Study Site

Lodz, Poland

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Cara Therapeutics Study Site

Szczecin, Poland

Location

Cara Therapeutics Study Site

Wroclaw, Poland

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Cara Therapeutics Study Site

Bucharest, Romania

Location

Cara Therapeutics Study Site

Oradea, Romania

Location

Cara Therapeutics Study Site

Timișoara, Romania

Location

Cara Therapeutics Study Site

Daegu, South Korea

Location

Cara Therapeutics Study Site 2

Goyang-si, South Korea

Location

Cara Therapeutics Study Site

Goyang-si, South Korea

Location

Cara Therapeutics Study Site

Seoul, 03080, South Korea

Location

Cara Therapeutics Study Site

Seoul, South Korea

Location

Cara Therapeutics Study Site

Almería, 04009, Spain

Location

Cara Therapeutics Study Site

Badalona, Spain

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Cara Therapeutics Study Site

Barcelona, Spain

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Cara Therapeutics Study Site

Ferrol, 15405, Spain

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Cara Therapeutics Study Site

Madrid, Spain

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Cara Therapeutics Study Site

Palma de Mallorca, Spain

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Cara Therapeutics Study Site 2

Valencia, Spain

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Cara Therapeutics Study Site

Valencia, Spain

Location

Cara Therapeutics Study Site

Vitoria-Gasteiz, Spain

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Pruritus; Kidney Failure, Chronic

Interventions

difelikefalin; Tablets

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Cara Therapeutics, PhD

  Cara Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Difelikefalin and placebo will be provided as enteric-coated tablets. All tablets are white in color with no markings and are identical in appearance. Difelikefalin tablets will be provided at doses of 1 mg.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo controlled study

Study Record Dates

• First Submitted: April 18, 2022
• First Posted: May 2, 2022
• Study Start: August 26, 2022
• Primary Completion: February 26, 2024
• Study Completion: February 26, 2024
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

BU (4); AR (6); US (9); ME (4); PL (7); RO (3); ES (9); DE (2); IT (4); KR (5); AU (10); HU (4); BR (8)