A Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (KALM-1)
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| ClinicalTrials.gov Identifier: NCT03422653 |
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Recruitment Status :
Completed
First Posted : February 6, 2018
Results First Posted : April 26, 2022
Last Update Posted : April 26, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Uremic Pruritus | Drug: CR845 0.5 mcg/kg Drug: Placebo | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 378 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, 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 : | February 20, 2018 |
| Actual Primary Completion Date : | April 6, 2019 |
| Actual Study Completion Date : | March 26, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: CR845 0.5mcg/kg
IV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)
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Drug: CR845 0.5 mcg/kg
IV medication delivered three times/week
Other Names:
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Placebo Comparator: Placebo
IV Placebo administered after each dialysis session (3 times/week)
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Drug: Placebo
IV medication delivered three times/week |
- 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 [ 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". LS means estimated percent, odds ratio and P value used a logistic regression model.
- 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. The 5-D Itch Scale has 5 questions; the total 5-D Itch Scale score ranges from 5 to 25, with higher scores indicating worse responses.
- 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. The Skindex-10 has 10 questions; the total Skindex-10 score ranges from 0 to 60. A lower total score represents better quality of life.
- 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 [ 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". LS means estimated percent, odds ratio and P value used a logistic regression model.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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;
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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.
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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.
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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.
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): NCT03422653
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| Study Director: | Frédérique Menzaghi, PhD | Cara Therapeutics |
Documents provided by Cara Therapeutics, Inc.:
| Responsible Party: | Cara Therapeutics, Inc. |
| ClinicalTrials.gov Identifier: | NCT03422653 |
| Other Study ID Numbers: |
CR845-CLIN3102 |
| First Posted: | February 6, 2018 Key Record Dates |
| Results First Posted: | April 26, 2022 |
| Last Update Posted: | April 26, 2022 |
| Last Verified: | March 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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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 |
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Pruritus Skin Diseases Skin Manifestations |