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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03636269




Registration number
NCT03636269
Ethics application status
Date submitted
3/08/2018
Date registered
17/08/2018
Date last updated
26/04/2022

Titles & IDs
Public title
CR845-CLIN3103: A Global Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus
Scientific 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
Secondary ID [1] 0 0
CR845-CLIN3103
Universal Trial Number (UTN)
Trial acronym
KALM-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Uremic Pruritus 0 0
Condition category
Condition code
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CR845 0.5 mcg/kg
Treatment: Drugs - Placebo

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

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


Treatment: Drugs: CR845 0.5 mcg/kg
IV CR845 0.5 mcg/kg administered three times/week

Treatment: Drugs: Placebo
IV placebo administered three times/week
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Week 12
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Week 12
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Baseline, Week 12
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Baseline, Week 12

Eligibility
Key inclusion criteria
Key

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/07/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/03/2020
Sample size
Target
Accrual to date
Final
473
Recruitment in Australia
Recruitment state(s)
NSW,TAS,VIC
Recruitment hospital [1] 0 0
Cara Therapeutics Study Site - Camperdown
Recruitment hospital [2] 0 0
Cara Therapeutics Study Site - Concord
Recruitment hospital [3] 0 0
Cara Therapeutics Study Site - Wahroonga
Recruitment hospital [4] 0 0
Cara Therapeutics Study Site - Westmead
Recruitment hospital [5] 0 0
Cara Therapeutics Study Site - Launceston
Recruitment hospital [6] 0 0
Cara Therapeutics Study Site - Clayton
Recruitment hospital [7] 0 0
Cara Therapeutics Study Site - Heidelberg
Recruitment hospital [8] 0 0
Cara Therapeutics Study Site - St Albans
Recruitment hospital [9] 0 0
Cara Therapeutics Study Site - Adelaide
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Concord
Recruitment postcode(s) [3] 0 0
2076 - Wahroonga
Recruitment postcode(s) [4] 0 0
- Westmead
Recruitment postcode(s) [5] 0 0
- Launceston
Recruitment postcode(s) [6] 0 0
- Clayton
Recruitment postcode(s) [7] 0 0
- Heidelberg
Recruitment postcode(s) [8] 0 0
- St Albans
Recruitment postcode(s) [9] 0 0
- Adelaide
Recruitment outside Australia
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United States of America
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California
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Colorado
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Utah
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Nova Scotia
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Ontario
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Baja
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Szeged
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Daegu
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Daejeon
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Goyang-si
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Guri-si
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Seogu
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Seoul
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Hamilton
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Brodnica
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Brzeg
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Bydgoszcz
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Grójec
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Kraków
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Kwidzyn
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Naklo Nad Notecia
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Olkusz
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Olsztyn
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Poznan
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Warsaw
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Wroclaw
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Zamosc
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Lódz
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Zyrardów
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Kaohsiung
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New Taipei City
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Taipei
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United Kingdom
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Belfast
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Ipswich
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United Kingdom
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Londonderry
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London
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Nottingham
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United Kingdom
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Westcliff-on-Sea

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Cara Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03636269
Trial related presentations / publications
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Frédérique Menzaghi, PhD
Address 0 0
Cara Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03636269