Clinical trial NCT03636269: CR845-CLIN3103: A Global Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus
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: Hemodialysis
difelikefalin
CR845
Pruritus
Chronic Itch
Itch
Itching
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: 2018-08-17
Enrollment: 473
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, international 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 randomized, double-blind, placebo-controlled 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, and a 12-week Double-blind Treatment 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 last dose of open-label study drug will be administered at the last dialysis visit on Week 52, or Early Termination.

Follow-up Period: 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: 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
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: 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
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Fountain Valley
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Northridge
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Riverside
country: United States
facility: Cara Therapeutics Study Site
state: California
city: San Dimas
country: United States
facility: Cara Therapeutics Study Site 2
state: California
city: San Dimas
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Westminster
country: United States
facility: Cara Therapeutics Study Site
state: Colorado
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: Orlando
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Athens
country: United States
facility: Cara Therapeutics Study Site
state: Georgia
city: Macon
country: United States
facility: Cara Therapeutics Study Site
state: Georgia
city: Baton Rouge
country: United States
facility: Cara Therapeutics Study Site
state: Louisiana
city: Brockton
country: United States
facility: Cara Therapeutics Study Site
state: Massachusetts
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: Saint Clair
country: United States
facility: Cara Therapeutics Study Site
state: Michigan
city: Tupelo
country: United States
facility: Cara Therapeutics Study Site
state: Mississippi
city: Saint Louis
country: United States
facility: Cara Therapeutics Study Site
state: Missouri
city: Clifton
country: United States
facility: Cara Therapeutics Study Site
state: New Jersey
city: Somerville
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: Long Island City
country: United States
facility: Cara Therapeutics Study Site
state: New York
city: Austin
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Dallas
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: McAllen
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: San Antonio
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Saint George
country: United States
facility: Cara Therapeutics Study Site
state: Utah
city: Roanoke
country: United States
facility: Cara Therapeutics Study Site
state: Virginia
city: Camperdown
country: Australia
facility: Cara Therapeutics Study Site
state: New South Wales
city: Concord
country: Australia
facility: Cara Therapeutics Study Site
state: New South Wales
city: Wahroonga
country: Australia
facility: Cara Therapeutics Study Site
state: New South Wales
city: Westmead
country: Australia
facility: Cara Therapeutics Study Site
state: New South Wales
city: Launceston
country: Australia
facility: Cara Therapeutics Study Site
state: Tasmania
city: Clayton
country: Australia
facility: Cara Therapeutics Study Site
state: Victoria
city: Heidelberg
country: Australia
facility: Cara Therapeutics Study Site
state: Victoria
city: St Albans
country: Australia
facility: Cara Therapeutics Study Site
state: Victoria
city: Adelaide
country: Australia
facility: Cara Therapeutics Study Site
city: Halifax
country: Canada
facility: Cara Therapeutics Study Site
state: Nova Scotia
city: Oshawa
country: Canada
facility: Cara Therapeutics Study Site
state: Ontario
city: Scarborough
country: Canada
facility: Cara Therapeutics Study Site
state: Ontario
city: Toronto
country: Canada
facility: Cara Therapeutics Study Site
state: Ontario
city: Montréal
country: Canada
facility: Cara Therapeutics Study Site
state: Quebec
city: Frýdek-Místek
country: Czechia
facility: Cara Therapeutics Study Site
city: Praha
country: Czechia
facility: Cara Therapeutics Study Site
city: Duesseldorf
country: Germany
facility: Cara Therapeutics Study Site
city: Heilbronn
country: Germany
facility: Cara Therapeutics Study Site
city: Baja
country: Hungary
facility: Cara Therapeutics Study Site
city: Debrecen
country: Hungary
facility: Cara Therapeutics Study Site
city: Pécs
country: Hungary
facility: Cara Therapeutics Study Site 2
city: Pécs
country: Hungary
facility: Cara Therapeutics Study Site
city: Szeged
country: Hungary
facility: Cara Therapeutics Study Site
city: Szekesfehervar
country: Hungary
facility: Cara Therapeutics Study Site
city: Szigetvár
country: Hungary
facility: Cara Therapeutics Study Site
city: Daegu
country: Korea, Republic of
facility: Cara Therapeutics Study Site
city: Daegu
country: Korea, Republic of
facility: Cara Therapeutics Study Site 2
city: Daejeon
country: Korea, Republic of
facility: Cara Therapeutics Study Site
city: Goyang-si
country: Korea, Republic of
facility: Cara Therapeutics Study Site
city: Guri-si
country: Korea, Republic of
facility: Cara Therapeutics Study Site
city: Seogu
country: Korea, Republic of
facility: Cara Therapeutics Study Site
city: Seoul
country: Korea, Republic of
facility: Cara Therapeutics Study Site 2
city: Seoul
country: Korea, Republic of
facility: Cara Therapeutics Study Site 3
city: Seoul
country: Korea, Republic of
facility: Cara Therapeutics Study Site
city: Auckland
country: New Zealand
facility: Cara Therapeutics Study Site
city: Hamilton
country: New Zealand
facility: Cara Therapeutics Study Site
city: New Plymouth
country: New Zealand
facility: Cara Therapeutics Study Site
city: Brodnica
country: Poland
facility: Cara Therapeutics Study Site
city: Brzeg
country: Poland
facility: Cara Therapeutics Study Site
city: Bydgoszcz
country: Poland
facility: Cara Therapeutics Study Site
city: Grójec
country: Poland
facility: Cara Therapeutics Study Site
city: Kraków
country: Poland
facility: Cara Therapeutics Study Site
city: Kwidzyn
country: Poland
facility: Cara Therapeutics Study Site
city: Nakło Nad Notecią
country: Poland
facility: Cara Therapeutics Study Site
city: Olkusz
country: Poland
facility: Cara Therapeutics Study Site
city: Olsztyn
country: Poland
facility: Cara Therapeutics Study Site
city: Poznań
country: Poland
facility: Cara Therapeutics Study Site
city: Warsaw
country: Poland
facility: Cara Therapeutics Study Site
city: Warszawa
country: Poland
facility: Cara Therapeutics Study Site
city: Wrocław
country: Poland
facility: Cara Therapeutics Study Site
city: Zamość
country: Poland
facility: Cara Therapeutics Study Site
city: Łódź
country: Poland
facility: Cara Therapeutics Study Site 2
city: Łódź
country: Poland
facility: Cara Therapeutics Study Site
city: Żyrardów
country: Poland
facility: Cara Therapeutics Study Site
city: Kaohsiung
country: Taiwan
facility: Cara Therapeutics Study Site
city: New Taipei City
country: Taiwan
facility: Cara Therapeutics Study Site
city: Taipei
country: Taiwan
facility: Cara Therapeutics Study Site 2
city: Taipei
country: Taiwan
facility: Cara Therapeutics Study Site
city: Belfast
country: United Kingdom
facility: Cara Therapeutics Study Site
city: Ipswich
country: United Kingdom
facility: Cara Therapeutics Study Site
city: Londonderry
country: United Kingdom
facility: Cara Therapeutics Study Site
city: London
country: United Kingdom
facility: Cara Therapeutics Study Site
city: Nottingham
country: United Kingdom
facility: Cara Therapeutics Study Site
city: Westcliff-on-Sea
country: United Kingdom
facility: Cara Therapeutics Study Site
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.