Clinical trial NCT03422653: A Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (KALM-1)
Official title: A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Intravenous CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus, With a 52-Week Open Label Extension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Uremic Pruritus
Keywords: CR845
Pruritus
Chronic Itch
Itch
Itching
difelikefalin
Hemodialysis
Uremic Pruritus
Dialysis
CKD
CKD-associated pruritus
CKD-aP
ESRD (end stage renal disease)
KALM
Chronic Kidney Disease
Kidney failure, chronic
Kidney dysfunction
Generalized pruritus
Lead sponsor: Cara Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-02-06
Enrollment: 378
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of intravenous (IV) CR845 at a dose of 0.5 mcg/kg administered after each dialysis session. The study includes a 12-week Double-blind Phase and a 52-week Open-label Extension Phase.

Detailed description: Double-blind Phase The Double-blind Phase of the study will consist of a Screening Visit, a 7-day Run-in Period, a 12 week Double-blind Treatment Period, and a 2-week Discontinuation Period. Informed consent will be obtained prior to performing any study-specific procedures. The Screening Visit will occur within 7 to 28 days prior to randomization to assess eligibility.

Open-label Extension Phase Patients who received at least 30 doses of study drug (either active or placebo) during the 12-week Double-blind Treatment Period and continue to meet other eligibility criteria will have the option to receive open label CR845 for an additional 52 weeks. The Open-label Extension Phase will be comprised of the Open-label Treatment Period and the Follow-up Period.

The last dose of open-label study drug will be administered at the last dialysis visit on Week 52, or Early Termination. A final safety Follow up Visit will be conducted 7-10 days after the End of Treatment/Early Termination Visit.

Eligibility criteria: Key Inclusion Criteria:

To be eligible for inclusion into the Double-blind Phase of the study, a patient must meet the following criteria:

* Has end-stage renal disease (ESRD) and has been on hemodialysis 3 times per week for at least 3 months prior to the start of screening;
* Has at least 2 single-pool Kt/V measurements ≥1.2, or at least 2 urea reduction ratio measurements ≥65%, or 1 single pool Kt/V measurement ≥1.2 and 1 urea reduction ratio measurement ≥65% on different dialysis days during the 3 months period prior to screening;
* Prior to randomization:

  * Has completed Worst Itching Intensity NRS worksheets up to 8 days prior to 1st dose;
  * Has a mean baseline Worst Itching Intensity NRS indicative of moderate to severe uremic pruritus.
* To be eligible for inclusion into the Open-label Extension Phase of the study, each patient will have to fulfill the additional key following criteria at the time of entry into the Open-label Extension Phase:

  * Has received at least 30 doses of the planned 36 doses of study drug during the Double-blind Phase of this study;
  * Continues to meet inclusion criteria.

Key Exclusion Criteria:

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

* Known noncompliance with dialysis treatment that in the opinion of the investigator would impede completion or validity of the study;
* Scheduled to receive a kidney transplant during the study;
* New or change of treatment received for itch including antihistamines and corticosteroids (oral, 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;
* Has pruritus only during the dialysis session (by patient report);
* Is receiving ongoing ultraviolet B and anticipates receiving such treatment during the study;
* Participated in a previous clinical study with CR845.
* A patient will be excluded from the Open-label Extension Phase of the study if any of the additional key following criteria are met at the time of entry into the Open-label Extension Phase:

  * Completed the Double-blind Phase of this study but exhibited adverse events during the course of the Treatment Period that may preclude continued exposure to the study drug;
  * Was noncompliant with protocol procedures during the Double-blind Phase of this study which is indicative of an inability to follow protocol procedures.

Primary outcomes:
measure: Reduction of Itch Intensity as Assessed by the Percentage of Patients Achieving an Improvement From Baseline ≥3 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) Score at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in 5-D Itch Scale Score at the End of Week 12
timeFrame: Baseline, Week 12
measure: Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in Total Skindex-10 Scale Score at the End of Week 12
timeFrame: Baseline, Week 12
measure: Reduction of Itch Intensity as Assessed by the Percentage of Patients Achieving an Improvement From Baseline ≥4 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: Homewood
country: United States
facility: Cara Therapeutics Study Site
state: Alabama
city: Huntsville
country: United States
facility: Cara Therapeutics Study Site
state: Alabama
city: Bakersfield
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Beverly Hills
country: United States
facility: Cara Therapeutics Study Site 2
state: California
city: Beverly Hills
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Chula Vista
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Corona
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Escondido
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Fountain Valley
country: United States
facility: Cara Therapeutics Study Site
state: California
city: La Mesa
country: United States
facility: Cara Therapeutics
state: California
city: Long Beach
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Ontario
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Riverside
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Roseville
country: United States
facility: Cara Therapeutics Study Site
state: California
city: San Diego
country: United States
facility: Cara Therapeutics Study Site
state: California
city: San Dimas
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Tarzana
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Denver
country: United States
facility: Cara Therapeutics Study Site
state: Colorado
city: Bridgeport
country: United States
facility: Cara Therapeutics Study Site
state: Connecticut
city: Hartford
country: United States
facility: Cara Therapeutics Study Site
state: Connecticut
city: Middlebury
country: United States
facility: Cara Therapeutics Study Site
state: Connecticut
city: Coral Springs
country: United States
facility: Cara Therapeutics Study Site 1
state: Florida
city: Hialeah
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Miami Gardens
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Miami
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Tampa
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Kalamazoo
country: United States
facility: Cara Therapeutics Study Site
state: Michigan
city: Roseville
country: United States
facility: Cara Therapeutics Study Site
state: Michigan
city: Minneapolis
country: United States
facility: Cara Therapeutics Study Site
state: Minnesota
city: Brookhaven
country: United States
facility: Cara Therapeutics Study Site
state: Mississippi
city: McComb
country: United States
facility: Cara Therapeutics Study Site
state: Mississippi
city: Tupelo
country: United States
facility: Cara Therapeutics Study Site
state: Mississippi
city: Kansas City
country: United States
facility: Cara Therapeutics Study Site
state: Missouri
city: Las Vegas
country: United States
facility: Cara Therapeutics Study Site
state: Nevada
city: Las Vegas
country: United States
facility: Cara Therapeutics Study Site
state: Nevada
city: Eatontown
country: United States
facility: Cara Therapeutics Study Site
state: New Jersey
city: Albuquerque
country: United States
facility: Cara Therapeutics Study Site
state: New Mexico
city: Gallup
country: United States
facility: Cara Therapeutics Study Site
state: New Mexico
city: Bronx
country: United States
facility: Cara Therapeutics Study Site
state: New York
city: Fresh Meadows
country: United States
facility: Cara Therapeutics Study Site
state: New York
city: Great Neck
country: United States
facility: Cara Therapeutics Study Site
state: New York
city: Durham
country: United States
facility: Cara Therapeutics Study Site
state: North Carolina
city: Canton
country: United States
facility: Cara Therapeutics Study Site
state: Ohio
city: Roseburg
country: United States
facility: Cara Therapeutics Study Site
state: Oregon
city: Chattanooga
country: United States
facility: Cara Therapeutics Study Site
state: Tennessee
city: Dallas
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Duncanville
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Greenville
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Houston
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Lewisville
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: McAllen
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Mesquite
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: San Antonio
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Waxahachie
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Chesapeake
country: United States
facility: Cara Therapeutics Study Site
state: Virginia
city: Hampton
country: United States
facility: Cara Therapeutics Study Site
state: Virginia
city: Wauwatosa
country: United States
facility: Cara Therapeutics Study Site
state: Wisconsin
Study officials:
affiliation: Cara Therapeutics
name: Frédérique Menzaghi, PhD
role: STUDY_DIRECTOR
References:
citation: Fishbane S, Wen W, Munera C, Lin R, Bagal S, McCafferty K, Menzaghi F, Goncalves J. Safety and Tolerability of Difelikefalin for the Treatment of Moderate to Severe Pruritus in Hemodialysis Patients: Pooled Analysis From the Phase 3 Clinical Trial Program. Kidney Med. 2022 Jun 28;4(8):100513. doi: 10.1016/j.xkme.2022.100513. eCollection 2022 Aug.
citation: Topf J, Wooldridge T, McCafferty K, Schomig M, Csiky B, Zwiech R, Wen W, Bhaduri S, Munera C, Lin R, Jebara A, Cirulli J, Menzaghi F. Efficacy of Difelikefalin for the Treatment of Moderate to Severe Pruritus in Hemodialysis Patients: Pooled Analysis of KALM-1 and KALM-2 Phase 3 Studies. Kidney Med. 2022 Jun 28;4(8):100512. doi: 10.1016/j.xkme.2022.100512. eCollection 2022 Aug.
citation: Hercz D, Jiang SH, Webster AC. Interventions for itch in people with advanced chronic kidney disease. Cochrane Database Syst Rev. 2020 Dec 7;12(12):CD011393. doi: 10.1002/14651858.CD011393.pub2.
citation: Fishbane S, Jamal A, Munera C, Wen W, Menzaghi F; KALM-1 Trial Investigators. A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus. N Engl J Med. 2020 Jan 16;382(3):222-232. doi: 10.1056/NEJMoa1912770. Epub 2019 Nov 8.