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

Uremic Pruritus Clinical Trial

— KALM-2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03636269
• Other study ID #: CR845-CLIN3103
• Status: Completed
• Phase: Phase 3
• Start date: July 17, 2018
• Est. completion date: March 30, 2020

Study information

• Verified date: March 2022
• Source: Cara Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 473
• Est. completion date: March 30, 2020
• Est. primary completion date: March 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pruritus
• Uremic Pruritus

Intervention

Drug:
• CR845 0.5 mcg/kg
IV CR845 0.5 mcg/kg administered three times/week
• Placebo
IV placebo administered three times/week

Locations

Country	Name	City	State
Australia	Cara Therapeutics Study Site	Adelaide
Australia	Cara Therapeutics Study Site	Camperdown	New South Wales
Australia	Cara Therapeutics Study Site	Clayton	Victoria
Australia	Cara Therapeutics Study Site	Concord	New South Wales
Australia	Cara Therapeutics Study Site	Heidelberg	Victoria
Australia	Cara Therapeutics Study Site	Launceston	Tasmania
Australia	Cara Therapeutics Study Site	St Albans	Victoria
Australia	Cara Therapeutics Study Site	Wahroonga	New South Wales
Australia	Cara Therapeutics Study Site	Westmead	New South Wales
Canada	Cara Therapeutics Study Site	Halifax	Nova Scotia
Canada	Cara Therapeutics Study Site	Montréal	Quebec
Canada	Cara Therapeutics Study Site	Oshawa	Ontario
Canada	Cara Therapeutics Study Site	Scarborough	Ontario
Canada	Cara Therapeutics Study Site	Toronto	Ontario
Czechia	Cara Therapeutics Study Site	Frýdek-Místek
Czechia	Cara Therapeutics Study Site	Praha
Germany	Cara Therapeutics Study Site	Duesseldorf
Germany	Cara Therapeutics Study Site	Heilbronn
Hungary	Cara Therapeutics Study Site	Baja
Hungary	Cara Therapeutics Study Site	Debrecen
Hungary	Cara Therapeutics Study Site	Pécs
Hungary	Cara Therapeutics Study Site 2	Pécs
Hungary	Cara Therapeutics Study Site	Szeged
Hungary	Cara Therapeutics Study Site	Szekesfehervar
Hungary	Cara Therapeutics Study Site	Szigetvár
Korea, Republic of	Cara Therapeutics Study Site	Daegu
Korea, Republic of	Cara Therapeutics Study Site 2	Daegu
Korea, Republic of	Cara Therapeutics Study Site	Daejeon
Korea, Republic of	Cara Therapeutics Study Site	Goyang-si
Korea, Republic of	Cara Therapeutics Study Site	Guri-si
Korea, Republic of	Cara Therapeutics Study Site	Seogu
Korea, Republic of	Cara Therapeutics Study Site	Seoul
Korea, Republic of	Cara Therapeutics Study Site 2	Seoul
Korea, Republic of	Cara Therapeutics Study Site 3	Seoul
New Zealand	Cara Therapeutics Study Site	Auckland
New Zealand	Cara Therapeutics Study Site	Hamilton
New Zealand	Cara Therapeutics Study Site	New Plymouth
Poland	Cara Therapeutics Study Site	Brodnica
Poland	Cara Therapeutics Study Site	Brzeg
Poland	Cara Therapeutics Study Site	Bydgoszcz
Poland	Cara Therapeutics Study Site	Grójec
Poland	Cara Therapeutics Study Site	Kraków
Poland	Cara Therapeutics Study Site	Kwidzyn
Poland	Cara Therapeutics Study Site	Lódz
Poland	Cara Therapeutics Study Site 2	Lódz
Poland	Cara Therapeutics Study Site	Naklo Nad Notecia
Poland	Cara Therapeutics Study Site	Olkusz
Poland	Cara Therapeutics Study Site	Olsztyn
Poland	Cara Therapeutics Study Site	Poznan
Poland	Cara Therapeutics Study Site	Warsaw
Poland	Cara Therapeutics Study Site	Warszawa
Poland	Cara Therapeutics Study Site	Wroclaw
Poland	Cara Therapeutics Study Site	Zamosc
Poland	Cara Therapeutics Study Site	Zyrardów
Taiwan	Cara Therapeutics Study Site	Kaohsiung
Taiwan	Cara Therapeutics Study Site	New Taipei City
Taiwan	Cara Therapeutics Study Site	Taipei
Taiwan	Cara Therapeutics Study Site 2	Taipei
United Kingdom	Cara Therapeutics Study Site	Belfast
United Kingdom	Cara Therapeutics Study Site	Ipswich
United Kingdom	Cara Therapeutics Study Site	London
United Kingdom	Cara Therapeutics Study Site	Londonderry
United Kingdom	Cara Therapeutics Study Site	Nottingham
United Kingdom	Cara Therapeutics Study Site	Westcliff-on-Sea
United States	Cara Therapeutics Study Site	Albuquerque	New Mexico
United States	Cara Therapeutics Study Site	Athens	Georgia
United States	Cara Therapeutics Study Site	Austin	Texas
United States	Cara Therapeutics Study Site	Baton Rouge	Louisiana
United States	Cara Therapeutics Study Site	Brockton	Massachusetts
United States	Cara Therapeutics Study Site	Chula Vista	California
United States	Cara Therapeutics Study Site	Clifton	New Jersey
United States	Cara Therapeutics Study Site	Dallas	Texas
United States	Cara Therapeutics Study Site	Fountain Valley	California
United States	Cara Therapeutics Study Site	Hialeah	Florida
United States	Cara Therapeutics Study Site	Kalamazoo	Michigan
United States	Cara Therapeutics Study Site	Long Island City	New York
United States	Cara Therapeutics Study Site	Macon	Georgia
United States	Cara Therapeutics Study Site	McAllen	Texas
United States	Cara Therapeutics Study Site	Miami Gardens	Florida
United States	Cara Therapeutics Study Site	Northridge	California
United States	Cara Therapeutics Study Site	Orlando	Florida
United States	Cara Therapeutics Study Site	Riverside	California
United States	Cara Therapeutics Study Site	Roanoke	Virginia
United States	Cara Therapeutics Study Site	Roseville	Michigan
United States	Cara Therapeutics Study Site	Saint Clair	Michigan
United States	Cara Therapeutics Study Site	Saint George	Utah
United States	Cara Therapeutics Study Site	Saint Louis	Missouri
United States	Cara Therapeutics Study Site	San Antonio	Texas
United States	Cara Therapeutics Study Site	San Dimas	California
United States	Cara Therapeutics Study Site 2	San Dimas	California
United States	Cara Therapeutics Study Site	Somerville	New Jersey
United States	Cara Therapeutics Study Site	Tupelo	Mississippi
United States	Cara Therapeutics Study Site	Westminster	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Cara Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  Germany,  Hungary,  Korea, Republic of,  New Zealand,  Poland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Week 12
Secondary	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	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.	Week 12
Secondary	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. 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.	Baseline, Week 12
Secondary	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. 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.	Baseline, Week 12