Study to Evaluate the Safety and Efficacy of Oral CR845 (Difelikefalin) in Patients With Primary Biliary Cholangitis (PBC) and Moderate-to-Severe Pruritus

A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Oral CR845 in Patients With Primary Biliary Cholangitis (PBC) and Moderate-to-Severe Pruritus

This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of twice-daily (BID) oral CR845 1.0 mg in patients with PBC with moderate-to-severe pruritus. The study includes a 16-week Treatment Period.

Study Overview

• Status: Terminated
• Conditions: Cholestatic Pruritus
• Intervention / Treatment: Drug: Placebo; Drug: CR845 1.0 mg

Detailed Description

This study will consist of a Screening Visit, a 7-day Run-in Period, a 16-week Treatment Period, and a Follow-up Visit (approximately 7-10 days after the last dose of study drug). 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.

Day 1 of the Treatment Period will be defined as the day of the administration of the first dose of study drug. If patients continue to meet all inclusion and no exclusion criteria at the end of the 7-day Run-in Period, they will be randomized in a 1:1 ratio to receive either placebo or CR845 tablets at a dose of 1.0 mg orally BID for 16 weeks.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Coronado, California, United States, 92118
      • Cara Therapeutics Study Site
    • Rialto, California, United States, 92377
      • Cara Therapeutics Study Site
    • San Francisco, California, United States, 94114
      • Cara Therapeutics Study Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Cara Therapeutics Study Site
  • Florida
    • Miami, Florida, United States, 33136
      • Cara Therapeutics Study Site
    • Plantation, Florida, United States, 33322
      • Cara Therapeutics Study Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Cara Therapeutics Study Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Cara Therapeutics Study Site 2
    • Boston, Massachusetts, United States, 02215
      • Cara Therapeutics Study Site
  • New York
    • New York, New York, United States, 10065
      • Cara Therapeutics Study Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Cara Therapeutics Study Site
  • Texas
    • Arlington, Texas, United States, 76012
      • Cara Therapeutics Study Site
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Cara Therapeutics Study Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Cara Therapeutics Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

To be eligible for inclusion into the study, a patient must meet the following criteria:

• Confirmed diagnosis of PBC;
• If currently taking ursodeoxycholic acid (UDCA), should be on stable dose for >12 weeks prior to screening and plan on continuing to take UDCA throughout the study;
• If previously taking UDCA, should have discontinued its use >12 weeks prior to screening;
• Self-reports experiencing daily or near-daily pruritus during the month prior to screening;
• Prior to randomization has a mean baseline WI-NRS score indicative of moderate to severe pruritus.

Key Exclusion Criteria:

A patient will be excluded from the study if any of the following criteria are met:

• Presence of Child-Pugh Class C decompensated cirrhosis at screening;
• Itching secondary to biliary obstruction;
• History or presence of hepatocellular carcinoma, hepatic abscess, or acute portal vein thrombosis;
• Current placement on liver transplantation list with anticipated liver transplant during the course of the study or current Model for End-stage Liver Disease (MELD) score ≥15;
• Alanine aminotransferase or aspartate aminotransferase >5 × upper limit of normal at screening, or within 2 months prior to screening;
• Anticipates receiving an opioid antagonist (eg, naloxone, naltrexone) or opioid-mixed agonist-antagonist (eg, buprenorphine, nalbuphine) from the start of screening through the end of the Treatment Period;
• New or change of treatment with antihistamines and corticosteroids (oral, intravenous, or topical), opioids, gabapentin, pregabalin, cholestyramine, rifampicin or fibrates within 14 days prior to screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Oral placebo tablet administered twice daily	Drug: Placebo; Oral Placebo administered twice daily
Active Comparator: CR845 1.0 mg; Oral CR845 1.0 mg tablet administered twice daily	Drug: CR845 1.0 mg; Oral CR845 1.0 mg administered twice daily; Other Names: Difelikefalin; CR845

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to Week 16 with respect to the weekly mean of the daily 24-hour Worst Itching Intensity Numeric Rating Scale (WI-NRS) score.	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".	Baseline, Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in itch-related quality of life as assessed by the change from baseline to Week 16 in total Skindex-10 Scale score	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.	Baseline, Week 16
Improvement in itch-related quality of life as assessed by the change from baseline to Week 16 in 5-D Itch Scale score	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.	Baseline, Week 16
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 WI-NRS score at Week 16	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".	Week 16

Collaborators and Investigators

• Sponsor: Cara Therapeutics, Inc.
• Investigators: Study Director: Frédérique Menzaghi, PhD, Cara Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2019
• Primary Completion (Actual): June 29, 2022
• Study Completion (Actual): June 29, 2022

Study Registration Dates

• First Submitted: June 19, 2019
• First Submitted That Met QC Criteria: June 19, 2019
• First Posted (Actual): June 21, 2019

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 28, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Itch; Pruritus; Primary Biliary Cholangitis; Itching; CR845; Chronic Itch; difelikefalin; Generalized pruritus
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Skin Diseases; Liver Diseases; Fibrosis; Skin Manifestations; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Pruritus; Cholangitis; Liver Cirrhosis, Biliary
• Other Study ID Numbers: CR845-210401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No