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

NCT02858726 | Completed Phase 2 Results DMC

• 1 other identifier: CR845-CLIN2101
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 29

Brief Summary

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.

Conditions

Uremic Pruritus

Keywords

Hemodialysis; CR845; Kappa opioid; Anti-itch; difelikefalin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

  Baseline, Week 8

Study Arms (4)

CR845 0.5mcg/kg

EXPERIMENTAL

Part A of study: IV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)

Drug: CR845 0.5 mcg/kg

CR845 1 mcg/kg

EXPERIMENTAL

Part A of study: IV CR845 1 mcg/kg administered after each dialysis session (3 times/week)

Drug: CR845 1 mcg/kg

CR845 1.5mcg/kg

EXPERIMENTAL

Part A of study: IV CR845 1.5 mcg/kg administered after each dialysis session (3 times/week)

Drug: CR845 1.5mcg/kg

Placebo

PLACEBO COMPARATOR

Part A of study: IV Placebo administered after each dialysis session (3 times/week)

Drug: Placebo

Interventions

CR845 0.5 mcg/kg DRUG

IV medication delivered three times/week

Also known as: CR845

CR845 0.5mcg/kg

CR845 1 mcg/kg DRUG

IV medication delivered three times/week

Also known as: CR845

CR845 1 mcg/kg

CR845 1.5mcg/kg DRUG

IV medication delivered three times/week

Also known as: CR845

CR845 1.5mcg/kg

Placebo DRUG

IV medication delivered three times/week

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent prior to participating in this study;
• Able to communicate clearly with the Investigator and staff, able to read, complete questionnaires, and understand the study procedures;
• Males or females 18 years of age or older;
• ESRD patients who have been on hemodialysis 3 times per week for at least 3 months prior to the start of Screening;
• 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
• 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
• Weigh between 88.2 lb (40.0 kg) and 297.6 lb (135.0 kg).
• Patient must self-report pruritus in the month prior to screening.
• If patient is receiving treatment for itch, this treatment must be stable prior to screening and during treatment period.
• 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;
• Patient who self-categorize as moderate-to-severe itch.

You may not qualify if:

• 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);
• Anticipated to receive a kidney transplant during the study;
• Known history of allergic reaction to opiates, such as hives
• Known or suspected history of alcohol, narcotic, or other drug abuse or dependence within 12 months prior to Screening;
• 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;
• 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;
• 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;
• 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);
• Has localized itch restricted to the palms of the hands;
• Has pruritus only during the dialysis session (by patient report);
• 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;
• Used Salvia divinorum or Salvinorin A within 30 days prior to the start of Screening or is anticipated to use it during the study;
• Received ultraviolet B treatment within 30 days prior to the start of Screening or anticipated to receive such treatment during the study;
• Participated in a previous clinical trial with CR845.

Sponsors & Collaborators

• Cara Therapeutics, Inc.: lead

Study Sites (29)

Cara Therapeutics Investigator Site

Phoenix, Arizona, 85035, United States

Location

Cara Therapeutics Study Site

Pine Bluff, Arkansas, 71603, United States

Location

Cara Therapeutics Investigator Site

Long Beach, California, 90806, United States

Location

Cara Therapeutics Study Site

Northridge, California, 91324, United States

Location

Cara Therapeutics Study Site

Whittier, California, 90603, United States

Location

Cara Therapeutics Study Site

Denver, Colorado, 80218, United States

Location

Cara Therapeutics Study Site

Hollywood, Florida, 33024, United States

Location

Cara Therapeutics Study Site

Tampa, Florida, 33614, United States

Location

Cara Therapeutics Study Site

Winter Park, Florida, 32789, United States

Location

Cara Therapeutics Study Site

Augusta, Georgia, 30909, United States

Location

Cara Therapeutics Study Site

Meridian, Idaho, 83642, United States

Location

Cara Therapetics Study Site

Creve Coeur, Missouri, 63141, United States

Location

Cara Therapeutics Study Site

Kansas City, Missouri, 64111, United States

Location

Cara Therapeutics Study Site

Kansas City, Missouri, 64131, United States

Location

Cara Therapeutics Study Site

Omaha, Nebraska, 68124, United States

Location

Cara Therapetics Investigator Site

Albuquerque, New Mexico, 87109, United States

Location

Cara Therapeutics Study Site

Gallup, New Mexico, 87301, United States

Location

Cara Therapeutics Study Site

College Point, New York, 11385, United States

Location

Cara Therapeutics Investigator Site

Mineola, New York, 11501, United States

Location

Cara Therapeutics Investigator Site

Wilmington, North Carolina, 28401, United States

Location

Cara Therapeutics Study Site

Winston-Salem, North Carolina, 27103, United States

Location

Cara Therapeutics Study Site

Bethlehem, Pennsylvania, 18017, United States

Location

Cara Therapeutics Investigator Site

Philadelphia, Pennsylvania, 19140, United States

Location

Cara Therapeutics Study Site

Chattanooga, Tennessee, 37408, United States

Location

Cara Therapetics Study Site

Knoxville, Tennessee, 37920, United States

Location

Cara Therapeutics Study Site

San Antonio, Texas, 78221, United States

Location

Cara Therapeutics Study Site

San Antonio, Texas, 78229, United States

Location

Cara Therapeutics Study Site

San Antonio, Texas, 78251, United States

Location

Cara Therapeutics Study Site

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 33283264 DERIVED

Results Point of Contact

• Title: Frédérique Menzaghi, PhD
• Organization: Cara Therapeutics

clinicaltrials.gov@caratherapeutics.com

203-406-3700

Study Officials

• Frederique Menzaghi, PhD

  Cara Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2016
• First Posted: August 8, 2016
• Study Start: June 1, 2016
• Primary Completion: March 14, 2017
• Study Completion: March 14, 2017
• Last Updated: July 29, 2020
• Results First Posted: July 29, 2020

Record last verified: 2020-07

Locations

US (29)