Clinical trial NCT03998163: CR845-CLIN3105: A Study to Evaluate the Safety and Effectiveness of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus
Official title: An Open-Label, Multicenter Study to Evaluate the Safety and Effectiveness of Intravenous CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Uremic Pruritus
Keywords: Hemodialysis
Pruritus
Uremic Pruritus
Dialysis
CR845
Chronic Itch
CKD
CKD-associated pruritus
CKD-aP
ESRD (end stage renal disease)
difelikefalin
Itch
Itching
KALM
Chronic Kidney Disease
Kidney failure, chronic
Kidney dysfunction
Generalized pruritus
Lead sponsor: Cara Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-06-26
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label study to evaluate the safety and effectiveness of intravenous (IV) CR845 at a dose of 0.5 mcg/kg administered after each dialysis session. The study includes an up to 12-week Treatment Period.

Detailed description: Screening Period: The Screening Period includes a Screening Visit and a Run-In Period. Informed consent will be obtained prior to performing any study-specific procedures. The Screening Visit will occur within 21 days prior to the start of the Run-in Period. Patients will start the Run-in Period during the week prior to Treatment Period to complete eligibility verification.

Treatment Period: All scheduled study visits during the Treatment Period will be conducted on dialysis days. Patients will be administered CR845 as an IV bolus after the end of their dialysis during a Treatment Period of up to 12 weeks so that each patient will receive CR845 3 times weekly for a total of up to 36 doses. End of treatment (EOT) is defined as the first day of dialysis following the last dose of drug. The EOT procedures will be conducted on the dialysis visit following the last dose of study drug.

Follow-up Visit: A final safety Follow up Visit will be conducted 7-10 days after the EOT/Early Termination Visit.

Eligibility criteria: Key Inclusion Criteria:

To be eligible for inclusion into 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 Treatment:

  * Has completed at least 3 Worst Itching Intensity NRS questionnaires from the start of the Run-in Period up to and including the pre-dose assessment on Day 1;

Key Exclusion Criteria:

A patient will be excluded from 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;
* New or change of prescription for opioids, gabapentin, or pregabalin within 14 days prior to screening;
* Received another investigational drug within 30 days or five half-lives (whichever is longer) prior to the start of dosing or is planning to participate in another interventional clinical study while enrolled in this study;
* Has pruritus only during the dialysis session (by patient report);
* Is receiving ongoing ultraviolet B treatment and/or anticipates receiving such treatment during the study;
* Participated in a previous clinical study with CR845.

Primary outcomes:
measure: Number of Participants With AEs.
timeFrame: Up to Follow-Up Visit (Week 13-14)
Secondary outcomes:
Other outcomes:
Locations:
city: Escondido
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Riverside
country: United States
facility: Cara Therapeutics Study Site
state: California
city: San Diego
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Victorville
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Denver
country: United States
facility: Cara Therapeutics Study Site
state: Colorado
city: Middlebury
country: United States
facility: Cara Therapeutics Study Site
state: Connecticut
city: Norwich
country: United States
facility: Cara Therapeutics Study Site
state: Connecticut
city: Coral Gables
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Fort Lauderdale
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Hollywood
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 2
state: Florida
city: Tampa
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Albany
country: United States
facility: Cara Therapeutics Study Site
state: Georgia
city: Boston
country: United States
facility: Cara Therapeutics Study Site
state: Massachusetts
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: 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 2
state: Nevada
city: Great Neck
country: United States
facility: Cara Therapeutics Study Site
state: New York
city: Philadelphia
country: United States
facility: Cara Therapeutics Study Site
state: Pennsylvania
city: Spartanburg
country: United States
facility: Cara Therapeutics Study Site
state: South Carolina
city: Knoxville
country: United States
facility: Cara Therapeutics Study Site
state: Tennessee
city: Austin
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: Mansfield
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 2
state: Texas
city: San Antonio
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: San Antonio
country: United States
facility: Cara Therapeutics Study Site 3
state: Texas
city: Temple
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Havlíčkův Brod
country: Czechia
facility: Cara Therapeutics Study Site
city: Nové Město Na Moravě
country: Czechia
facility: Cara Therapeutics Study Site
city: Praha
country: Czechia
facility: Cara Therapeutics Study Site
city: Sokolov
country: Czechia
facility: Cara Therapeutics Study Site
city: Budapest
country: Hungary
facility: Cara Therapeutics Study Site 2
city: Budapest
country: Hungary
facility: Cara Therapeutics Study Site
city: Dunaújváros
country: Hungary
facility: Cara Therapeutics Study Site
city: Kaposvár
country: Hungary
facility: Cara Therapeutics Study Site
city: Kistarcsa
country: Hungary
facility: Cara Therapeutics Study Site
city: Nyíregyháza
country: Hungary
facility: Cara Therapeutics Study Site
city: Szombathely
country: Hungary
facility: Cara Therapeutics Study Site
city: Ostrołęka
country: Poland
facility: Cara Therapeutics Study Site
city: Radom
country: Poland
facility: Cara Therapeutics Study Site
city: Sochaczew
country: Poland
facility: Cara Therapeutics Study Site
Study officials:
affiliation: Cara Therapeutics
name: Frédérique Menzaghi, PhD
role: STUDY_DIRECTOR
References:
citation: Weiner DE, Vervloet MG, Walpen S, Schaufler T, Munera C, Menzaghi F, Wen W, Bhaduri S, Germain MJ; trial investigators. Safety and Effectiveness of Difelikefalin in Patients With Moderate-to-Severe Pruritus Undergoing Hemodialysis: An Open-Label, Multicenter Study. Kidney Med. 2022 Aug 24;4(10):100542. doi: 10.1016/j.xkme.2022.100542. eCollection 2022 Oct.
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.