CR845-CLIN3103: A Global Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus

NCT ID: NCT03636269

Last Updated: 2022-04-26

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

473 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-17

Study Completion Date

2020-03-30

Brief Summary

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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

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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.

Conditions

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Uremic Pruritus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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CR845 0.5mcg/kg

IV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)

Group Type ACTIVE_COMPARATOR

CR845 0.5 mcg/kg

Intervention Type DRUG

IV CR845 0.5 mcg/kg administered three times/week

Placebo

IV Placebo administered after each dialysis session (3 times/week)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

IV placebo administered three times/week

Interventions

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CR845 0.5 mcg/kg

IV CR845 0.5 mcg/kg administered three times/week

Intervention Type DRUG

Placebo

IV placebo administered three times/week

Intervention Type DRUG

Other Intervention Names

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CR845 Difelikefalin

Eligibility Criteria

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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;

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cara Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Frédérique Menzaghi, PhD

Role: STUDY_DIRECTOR

Cara Therapeutics

Locations

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Cara Therapeutics Study Site

Chula Vista, California, United States

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Fountain Valley, California, United States

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Northridge, California, United States

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Riverside, California, United States

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Cara Therapeutics Study Site 2

San Dimas, California, United States

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San Dimas, California, United States

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Westminster, Colorado, United States

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Hialeah, Florida, United States

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Miami Gardens, Florida, United States

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Orlando, Florida, United States

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Athens, Georgia, United States

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Macon, Georgia, United States

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Baton Rouge, Louisiana, United States

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Brockton, Massachusetts, United States

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Kalamazoo, Michigan, United States

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Roseville, Michigan, United States

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Saint Clair, Michigan, United States

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Tupelo, Mississippi, United States

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St Louis, Missouri, United States

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Clifton, New Jersey, United States

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Somerville, New Jersey, United States

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Albuquerque, New Mexico, United States

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Long Island City, New York, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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McAllen, Texas, United States

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San Antonio, Texas, United States

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St. George, Utah, United States

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Roanoke, Virginia, United States

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Camperdown, New South Wales, Australia

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Concord, New South Wales, Australia

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Wahroonga, New South Wales, Australia

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Westmead, New South Wales, Australia

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Launceston, Tasmania, Australia

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Clayton, Victoria, Australia

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Heidelberg, Victoria, Australia

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St Albans, Victoria, Australia

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Adelaide, , Australia

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Halifax, Nova Scotia, Canada

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Oshawa, Ontario, Canada

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Scarborough Village, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Frýdek-Místek, , Czechia

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Prague, , Czechia

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Düsseldorf, , Germany

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Heilbronn, , Germany

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Baja, , Hungary

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Debrecen, , Hungary

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Pécs, , Hungary

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Pécs, , Hungary

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Szeged, , Hungary

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Székesfehérvár, , Hungary

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Szigetvár, , Hungary

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Auckland, , New Zealand

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Hamilton, , New Zealand

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New Plymouth, , New Zealand

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Brodnica, , Poland

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Brzeg, , Poland

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Bydgoszcz, , Poland

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Grójec, , Poland

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Krakow, , Poland

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Kwidzyn, , Poland

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Lodz, , Poland

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Lodz, , Poland

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Nakło nad Notecią, , Poland

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Olkusz, , Poland

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Olsztyn, , Poland

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Poznan, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Zamość, , Poland

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Żyrardów, , Poland

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Daegu, , South Korea

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Daegu, , South Korea

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Daejeon, , South Korea

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Goyang-si, , South Korea

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Guri-si, , South Korea

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Seogu, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Kaohsiung City, , Taiwan

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New Taipei City, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Belfast, , United Kingdom

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Ipswich, , United Kingdom

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London, , United Kingdom

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Londonderry, , United Kingdom

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Nottingham, , United Kingdom

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Westcliff-on-Sea, , United Kingdom

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Countries

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United States Australia Canada Czechia Germany Hungary New Zealand Poland South Korea Taiwan United Kingdom

References

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Fishbane SN, Block GA, Evenepoel P, Budden J, Morin I, Menzaghi F, Wen W, Lerma EV. Pruritus Severity and Serum Phosphate in CKD: A Post Hoc Analysis of Difelikefalin Studies. Kidney360. 2024 Sep 1;5(9):1270-1280. doi: 10.34067/KID.0000000000000520. Epub 2024 Jul 22.

Reference Type DERIVED
PMID: 39037824 (View on PubMed)

Weiner DE, Schaufler T, McCafferty K, Kalantar-Zadeh K, Germain M, Ruessmann D, Morin I, Menzaghi F, Wen W, Stander S. Difelikefalin improves itch-related sleep disruption in patients undergoing haemodialysis. Nephrol Dial Transplant. 2024 Jun 28;39(7):1125-1137. doi: 10.1093/ndt/gfad245.

Reference Type DERIVED
PMID: 37968132 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36039153 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36016762 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33283264 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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CR845-CLIN3103

Identifier Type: -

Identifier Source: org_study_id

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