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CR845-CLIN3103: A Global Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (KALM-2)

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ClinicalTrials.gov Identifier: NCT03636269
Recruitment Status : Recruiting
First Posted : August 17, 2018
Last Update Posted : July 24, 2019
Sponsor:
Information provided by (Responsible Party):
Cara Therapeutics, Inc.

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.

Condition or disease Intervention/treatment Phase
Uremic Pruritus Drug: CR845 0.5 mcg/kg Drug: Placebo Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 350 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : July 17, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dialysis Itching

Arm Intervention/treatment
Active Comparator: CR845 0.5mcg/kg
IV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)
Drug: CR845 0.5 mcg/kg
IV CR845 0.5 mcg/kg administered three times/week
Other Names:
  • CR845
  • Difelikefalin

Placebo Comparator: Placebo
IV Placebo administered after each dialysis session (3 times/week)
Drug: Placebo
IV placebo administered three times/week




Primary Outcome Measures :
  1. Reduction of itch intensity as assessed by the proportion 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 [ Time Frame: Week 12 ]
    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".


Secondary Outcome Measures :
  1. 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 [ Time Frame: Baseline, Week 12 ]
    The 5-D Itch Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past 2 weeks. The questions cover five dimensions of itch including the degree, duration of itch/day, direction (improvement/worsening), disability (impact on activities such as work), and body distribution of itch. A lower total score represents better quality of life.

  2. 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 [ Time Frame: Baseline, Week 12 ]
    The Skindex-10 Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past week. The questions cover 3 domains: disease, mood/emotional distress, and social functioning domain. A lower total score represents better quality of life.

  3. Reduction of itch intensity as assessed by the proportion 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 [ Time Frame: Week 12 ]
    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".



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03636269


Contacts
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Contact: Georgine Ragsdale, PharmD 203-406-3700 clinicaltrials.gov@caratherapeutics.com

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Sponsors and Collaborators
Cara Therapeutics, Inc.
Investigators
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Study Director: Frédérique Menzaghi, PhD Cara Therapeutics

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Responsible Party: Cara Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03636269     History of Changes
Other Study ID Numbers: CR845-CLIN3103
First Posted: August 17, 2018    Key Record Dates
Last Update Posted: July 24, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Cara Therapeutics, Inc.:
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

Additional relevant MeSH terms:
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Pruritus
Skin Diseases
Skin Manifestations
Signs and Symptoms