Study to Evaluate IV CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus

A Two-Part, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Intravenous CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus

2 Part Study: Part A will assess 3 different dosing levels of IV CR845 versus placebo in patient on hemodialysis who have moderate-to-severe itching due to uremic pruritus. Patients will receive either CR845 or placebo after each dialysis session for eight weeks. The safety and efficacy of CR845 will be monitored throughout the study. A sub-group of patients will also have pharmacokinetic assessments completed. Part B of the study will assess one dose of IVCR845 versus placebo for 12 weeks in patients on hemodialysis who have moderate-to-severe itching. The dose of CR845 used in Part B will be based on safety and efficacy found in Part A.

Study Overview

• Status: Completed
• Conditions: Uremic Pruritus
• Intervention / Treatment: Drug: CR845 0.5 mcg/kg; Drug: CR845 1 mcg/kg; Drug: CR845 1.5mcg/kg; Drug: Placebo

Detailed Description

This is a two-part study. Patients participating in Part A will be consented and trained on the completion of questionnaires about the severity of itching and overall health. Patients will be required to complete questionnaires during their visits to the dialysis center and also while at home on other days. Results of the screening questionnaires will assess eligibility for the study. Additional laboratory tests and measurements for safety will also be completed during the screening period. Patients meeting all criteria for entry into Part A of the study will be randomized to receive either one of three different doses of CR845 or a placebo. Patients will receive the study drug for eight weeks IV after each hemodialysis treatment (i.e. 3 times per week). Assessments for intensity of itch and safety will also be completed during the 8 week treatment period. When patients have completed treatment, a Follow-up visit will be completed 7 days later.

Patients participating in Part B will be consented and trained on the completion of questionnaires about itching and overall health. Patients will be required to complete questionnaires during their visits to the dialysis center and also while at home on other days. Laboratory tests and measurements for safety will also be completed during the screening period to determine study eligibility. Patients meeting all criteria for entry into Part B of the study will be randomized to receive either CR845 or a placebo. The dose of CR845 used will have been determined based on the safety and efficacy from Part A. Patients will be dosed with either CR845 or placebo for twelve weeks after each hemodialysis treatment (i.e. 3 times per week). Assessments for intensity of itch and safety will be completed during the treatment period also. When patients have completed treatment, a Follow-up visit will be completed 7 days later.

• Study Type: Interventional
• Enrollment (Actual): 226
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85035
      • Cara Therapeutics Investigator Site
  • Arkansas
    • Pine Bluff, Arkansas, United States, 71603
      • Cara Therapeutics Study Site
  • California
    • Long Beach, California, United States, 90806
      • Cara Therapeutics Investigator Site
    • Northridge, California, United States, 91324
      • Cara Therapeutics Study Site
    • Whittier, California, United States, 90603
      • Cara Therapeutics Study Site
  • Colorado
    • Denver, Colorado, United States, 80218
      • Cara Therapeutics Study Site
  • Florida
    • Hollywood, Florida, United States, 33024
      • Cara Therapeutics Study Site
    • Tampa, Florida, United States, 33614
      • Cara Therapeutics Study Site
    • Winter Park, Florida, United States, 32789
      • Cara Therapeutics Study Site
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Cara Therapeutics Study Site
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Cara Therapeutics Study Site
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Cara Therapetics Study Site
    • Kansas City, Missouri, United States, 64111
      • Cara Therapeutics Study Site
    • Kansas City, Missouri, United States, 64131
      • Cara Therapeutics Study Site
  • Nebraska
    • Omaha, Nebraska, United States, 68124
      • Cara Therapeutics Study Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Cara Therapetics Investigator Site
    • Gallup, New Mexico, United States, 87301
      • Cara Therapeutics Study Site
  • New York
    • College Point, New York, United States, 11385
      • Cara Therapeutics Study Site
    • Mineola, New York, United States, 11501
      • Cara Therapeutics Investigator Site
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Cara Therapeutics Investigator Site
    • Winston-Salem, North Carolina, United States, 27103
      • Cara Therapeutics Study Site
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Cara Therapeutics Study Site
    • Philadelphia, Pennsylvania, United States, 19140
      • Cara Therapeutics Investigator Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37408
      • Cara Therapeutics Study Site
    • Knoxville, Tennessee, United States, 37920
      • Cara Therapetics Study Site
  • Texas
    • San Antonio, Texas, United States, 78221
      • Cara Therapeutics Study Site
    • San Antonio, Texas, United States, 78229
      • Cara Therapeutics Study Site
    • San Antonio, Texas, United States, 78251
      • Cara Therapeutics Study Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Cara Therapeutics Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Willing and able to provide written informed consent prior to participating in this study;
2. Able to communicate clearly with the Investigator and staff, able to read, complete questionnaires, and understand the study procedures;
3. Males or females 18 years of age or older;
4. ESRD patients who have been on hemodialysis 3 times per week for at least 3 months prior to the start of Screening;
5. Women of child-bearing potential must have a negative serum pregnancy test and agree to practice an acceptable form of birth control for the duration of the study
6. Male patients that are not biologically or surgically sterile must agree to practice an acceptable from of birth control for the duration of the study
7. Weigh between 88.2 lb (40.0 kg) and 297.6 lb (135.0 kg).
8. Patient must self-report pruritus in the month prior to screening.
9. If patient is receiving treatment for itch, this treatment must be stable prior to screening and during treatment period.
10. 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;
11. Patient who self-categorize as moderate-to-severe itch.

Exclusion Criteria:

1. Known to be non-compliant with dialysis treatment (i.e., has missed more than 2 dialysis sessions in the past 2 months because of non-compliance);
2. Anticipated to receive a kidney transplant during the study;
3. Known history of allergic reaction to opiates, such as hives
4. Known or suspected history of alcohol, narcotic, or other drug abuse or dependence within 12 months prior to Screening;
5. Patient has any clinically relevant acute or chronic medical or neuropsychiatric condition which, in the opinion of the Investigator, would pose undue risk to the patient, would impede completion of the study procedures, or would compromise the validity of the study measurements;
6. Serum alanine aminotransferase or aspartate aminotransferase greater than 2.5 times the reference upper limit of normal (ULN), or total bilirubin greater than 2 times ULN at Screening;
7. Received another investigational drug within 30 days prior to the start of Screening or has planned to participate in another clinical trial while enrolled in this study;
8. Has pruritus probably or definitely attributed to a cause other than ESRD or its complications (e.g., patients with concomitant pruritic dermatological disease or cholestatic liver disease would be excluded). (Note: Patients whose pruritus is attributed to ESRD complications such as hyperparathyroidism, hyperphosphatemia, anemia, or the dialysis procedure or prescription may be enrolled);
9. Has localized itch restricted to the palms of the hands;
10. Has pruritus only during the dialysis session (by patient report);
11. Anticipated to receive opioid antagonists (e.g., naloxone, naltrexone), or opioid mixed agonist-antagonist (e.g., buprenorphine, nalbuphine) from the start of Screening through the end of the Treatment Period;
12. Used Salvia divinorum or Salvinorin A within 30 days prior to the start of Screening or is anticipated to use it during the study;
13. Received ultraviolet B treatment within 30 days prior to the start of Screening or anticipated to receive such treatment during the study;
14. Participated in a previous clinical trial with CR845.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CR845 0.5mcg/kg; Part A of study: IV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)	Drug: CR845 0.5 mcg/kg; IV medication delivered three times/week; Other Names: CR845
Experimental: CR845 1 mcg/kg; Part A of study: IV CR845 1 mcg/kg administered after each dialysis session (3 times/week)	Drug: CR845 1 mcg/kg; IV medication delivered three times/week; Other Names: CR845
Experimental: CR845 1.5mcg/kg; Part A of study: IV CR845 1.5 mcg/kg administered after each dialysis session (3 times/week)	Drug: CR845 1.5mcg/kg; IV medication delivered three times/week; Other Names: CR845
Placebo Comparator: Placebo; Part A of study: IV Placebo administered after each dialysis session (3 times/week)	Drug: Placebo; IV medication delivered three times/week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score During Week 8	Intensity of itch was measured using a numerical rating scale (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". Higher scores meant worse itch intensity.	Baseline, Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 8	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. The minimum score is 0 and the maximum score is 60 (or total score can range from 0 to 60) with a higher score meaning a worse quality of life.	Baseline, Week 8

Collaborators and Investigators

• Sponsor: Cara Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): March 14, 2017
• Study Completion (Actual): March 14, 2017

Study Registration Dates

• First Submitted: July 29, 2016
• First Submitted That Met QC Criteria: August 3, 2016
• First Posted (Estimate): August 8, 2016

Study Record Updates

• Last Update Posted (Actual): July 29, 2020
• Last Update Submitted That Met QC Criteria: July 15, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Hemodialysis; CR845; difelikefalin; Kappa opioid; Anti-itch
• Additional Relevant MeSH Terms: Skin Diseases; Skin Manifestations; Pruritus
• Other Study ID Numbers: CR845-CLIN2101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided