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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03636269
Ethics application status
Date submitted
3/08/2018
Date registered
17/08/2018
Date last updated
24/07/2019

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 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 - 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".
Timepoint [1] 0 0
Week 12
Secondary outcome [1] 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 - 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.
Timepoint [1] 0 0
Baseline, 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 - 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.
Timepoint [2] 0 0
Baseline, Week 12
Secondary outcome [3] 0 0
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 - 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".
Timepoint [3] 0 0
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
Gender
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Cara Therapeutics Study Site - Concord
Recruitment hospital [2] 0 0
Cara Therapeutics Study Site - Wahroonga
Recruitment hospital [3] 0 0
Cara Therapeutics Study Site - Clayton
Recruitment hospital [4] 0 0
Cara Therapeutics Study Site - Heidelberg
Recruitment hospital [5] 0 0
Cara Therapeutics Study Site - St Albans
Recruitment postcode(s) [1] 0 0
- Concord
Recruitment postcode(s) [2] 0 0
2076 - Wahroonga
Recruitment postcode(s) [3] 0 0
- Clayton
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
- St Albans
Recruitment outside Australia
Country [1] 0 0
United States of America
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California
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Colorado
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Florida
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Georgia
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Louisiana
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Massachusetts
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Michigan
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Mississippi
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Missouri
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New Mexico
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New York
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Texas
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Utah
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Canada
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Nova Scotia
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Canada
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Ontario
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Quebec
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Germany
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Heilbronn
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Hungary
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Baja
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Hungary
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Szeged
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Hungary
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Szekesfehervar
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Hungary
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Szigetvár
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Korea, Republic of
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Busan
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Daegu
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Daejeon
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Gwangju
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Seoul
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New Zealand
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Auckland
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New Zealand
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Hamilton
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New Zealand
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New Plymouth
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Poland
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Brodnica
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Brzeg
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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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Poznan
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Wroclaw
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Zamosc
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Lódz
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Zyrardów
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Taiwan
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Taichung city
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United Kingdom
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Belfast
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United Kingdom
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Ipswich
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Londonderry
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United Kingdom
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London
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United Kingdom
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Nottingham

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/show/NCT03636269
Trial related presentations / publications
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
Georgine Ragsdale, PharmD
Address 0 0
Country 0 0
Phone 0 0
203-406-3700
Fax 0 0
Email 0 0
clinicaltrials.gov@caratherapeutics.com
Contact person for scientific queries

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