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

NCT05342623 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: CR845-310301
• Study Type: interventional
• Target: 286
• Locations: 1 country
• Sites: 83

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 (83)

Cara Therapeutics Study Site

Huntsville, Alabama, 35805, United States

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Cara Therapeutics Study Site

Phoenix, Arizona, 85016, United States

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Cara Therapeutics Study Site

Surprise, Arizona, 85374, United States

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Cara Therapeutics Study Site

Anaheim, California, 92801, United States

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Cara Therapeutics Study Site

Bakersfield, California, 93308, United States

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Cara Therapeutics Study Site

Beverly Hills, California, 90211, United States

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Cara Therapeutics Study Site

Chula Vista, California, 91910, United States

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Cara Therapeutics Study Site

El Centro, California, 92243, United States

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Cara Therapeutics Study Site

Garden Grove, California, 92844, United States

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Cara Therapeutics Study Site

La Mesa, California, 91942, United States

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Cara Therapeutics Study Site

Northridge, California, 91324, United States

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Cara Therapeutics Study Site

Ontario, California, 91762, United States

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Cara Therapeutics Study Site

Riverside, California, 92505, United States

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Cara Therapeutics Study Site

Santa Clara, California, 91351, United States

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Cara Therapeutics Study Site

South Gate, California, 90280, United States

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Cara Therapeutics Study Site

Tarzana, California, 91356, United States

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Cara Therapeutics Study Site

Vacaville, California, 95687, United States

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Cara Therapeutics Study Site

Valencia, California, 91355, United States

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Cara Therapeutics Study Site

Victorville, California, 92392, United States

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Cara Therapeutics Study Site

Arvada, Colorado, 80002, United States

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Cara Therapeutics Study Site

Denver, Colorado, 80230, United States

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Cara Therapeutics Study Site

New Haven, Connecticut, 06511, United States

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Cara Therapeutics Study Site

Atlantis, Florida, 33462, United States

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Cara Therapeutics Study Site

Cape Coral, Florida, 33914, United States

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Cara Therapeutics Study Site

Coral Gables, Florida, 33134, United States

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Cara Therapeutics Study Site

Fort Lauderdale, Florida, 33308, United States

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Cara Therapeutics Study Site

Hialeah, Florida, 33010, United States

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Cara Therapeutics Study Site

Miami, Florida, 33143, United States

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Cara Therapeutics Study Site

Miami, Florida, 33173, United States

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Cara Therapeutics Study Site

Orange City, Florida, 32763, United States

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Cara Therapeutics Study Site 2

Orlando, Florida, 32806, United States

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Cara Therapeutics Study Site

Orlando, Florida, 32808, United States

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Cara Therapeutics Study Site

Pembroke Pines, Florida, 33024, United States

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Cara Therapeutics Study Site

Riverview, Florida, 33578, United States

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Cara Therapeutics Study Site

Tampa, Florida, 33603, United States

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Cara Therapeutics Study Site

West Palm Beach, Florida, 33401, United States

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Cara Therapeutics Study Site

Albany, Georgia, 31701, United States

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Cara Therapeutics Study Site

East Point, Georgia, 30344, United States

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Cara Therapeutics Study Site

Nampa, Idaho, 83687, United States

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Cara Therapeutics Study Site

Huntley, Illinois, 60142, United States

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Cara Therapeutics Study Site

Palos Hills, Illinois, 60465, United States

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Cara Therapeutics Study Site

Kansas City, Kansas, 48504, United States

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Cara Therapeutics Study Site

Louisville, Kentucky, 40205, United States

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Cara Therapeutics Study Site

Baton Rouge, Louisiana, 70808, United States

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Cara Therapeutics Study Site

Metairie, Louisiana, 70006, United States

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Cara Therapeutics Study Site

Shreveport, Louisiana, 71101, United States

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Cara Therapeutics Study Site

Zachary, Louisiana, 70791, United States

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Cara Therapeutics Study Site

Boston, Massachusetts, 02111, United States

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Cara Therapeutics Study Site

Flint, Michigan, 48504, United States

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Cara Therapeutics Study Site

Kalamazoo, Michigan, 49007, United States

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Cara Therapeutics Study Site

Roseville, Michigan, 48066, United States

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Cara Therapeutics Study Site

Saint Clair, Michigan, 48081, United States

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Cara Therapeutics Study Site

Saint Joseph, Michigan, 49085, United States

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Cara Therapeutics Study Site

Tupelo, Mississippi, 38801, United States

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Cara Therapeutics Study Site

Kansas City, Missouri, 64131, United States

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Cara Therapeutics Study Site

Las Vegas, Nevada, 89128, United States

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Cara Therapeutics Study Site

Laurelton, New York, 11413, United States

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Cara Therapeutics Study Site

The Bronx, New York, 10455, United States

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Cara Therapeutics Study Site

Durham, North Carolina, 27704, United States

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Cara Therapeutics Study Site

Columbus, Ohio, 43215, United States

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Cara Therapeutics Study Site

Lima, Ohio, 45805, United States

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Cara Therapeutics Study Site

Ardmore, Oklahoma, 73401, United States

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Cara Therapeutics Study Site

Bethlehem, Pennsylvania, 18107, United States

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Cara Therapeutics Study Site

Upland, Pennsylvania, 19013, United States

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Cara Therapeutics Study Site

East Providence, Rhode Island, 02914, United States

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Cara Therapeutics Study Site

Providence, Rhode Island, 02904, United States

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Cara Therapeutics Study Site

Spartanburg, South Carolina, 29302, United States

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Cara Therapeutics Study Site

Chattanooga, Tennessee, 37404, United States

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Cara Therapeutics Study Site

Jackson, Tennessee, 38305, United States

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Cara Therapeutics Study Site

Knoxville, Tennessee, 37924, United States

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Cara Therapeutics Study Site

Austin, Texas, 78751, United States

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Cara Therapeutics Study Sites

Corsicana, Texas, 75110, United States

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Cara Therapeutics Study Site

El Paso, Texas, 79902, United States

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Cara Therapeutics Study Site

Greenville, Texas, 75402, United States

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Cara Therapeutics Study Site

Houston, Texas, 77079, United States

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Cara Therapeutics Study Site

Houston, Texas, 77081, United States

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Cara Therapeutics Study Site 2

Houston, Texas, 77099, United States

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Cara Therapeutics Study Site

Lewisville, Texas, 75057, United States

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Cara Therapeutics Study Site

McAllen, Texas, 78503, United States

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Cara Therapeutics Study Site

McKinney, Texas, 75069, United States

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Cara Therapeutics Study Site

Pasadena, Texas, 77504, United States

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Cara Therapeutics Study Site

Sherman, Texas, 75090, United States

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Cara Therapeutics Study Site

Hampton, Virginia, 23666, United States

Location

Related Publications (1)

• Didik S, Golosova D, Xu B, Staruschenko A. Opioids and the Kidney: A Compendium. Kidney360. 2023 Dec 1;4(12):1816-1823. doi: 10.34067/KID.0000000000000291. Epub 2023 Nov 6.

  PMID: 37927032 DERIVED

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

  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: April 22, 2022
• Study Start: May 17, 2022
• Primary Completion: February 29, 2024
• Study Completion: February 29, 2024
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (83)