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

NCT03995212 | Terminated Phase 2 FDA Drug

• 1 other identifier: CR845-210401
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 14

Brief Summary

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.

Conditions

Cholestatic Pruritus

Keywords

Primary Biliary Cholangitis; Pruritus; CR845; Chronic Itch; difelikefalin; Itch; Itching; Generalized pruritus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Improvement in itch-related quality of life as assessed by the change from baseline to Week 16 in total Skindex-10 Scale score

  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

  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

  Week 16

Study Arms (2)

CR845 1.0 mg

ACTIVE COMPARATOR

Oral CR845 1.0 mg tablet administered twice daily

Drug: CR845 1.0 mg

Placebo

PLACEBO COMPARATOR

Oral placebo tablet administered twice daily

Drug: Placebo

Interventions

CR845 1.0 mg DRUG

Oral CR845 1.0 mg administered twice daily

Also known as: CR845, Difelikefalin

CR845 1.0 mg

Placebo DRUG

Oral Placebo administered twice daily

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cara Therapeutics, Inc.: lead

Study Sites (14)

Cara Therapeutics Study Site

Coronado, California, 92118, United States

Location

Cara Therapeutics Study Site

Rialto, California, 92377, United States

Location

Cara Therapeutics Study Site

San Francisco, California, 94114, United States

Location

Cara Therapeutics Study Site

Colorado Springs, Colorado, 80907, United States

Location

Cara Therapeutics Study Site

Miami, Florida, 33136, United States

Location

Cara Therapeutics Study Site

Plantation, Florida, 33322, United States

Location

Cara Therapeutics Study Site

Indianapolis, Indiana, 46202, United States

Location

Cara Therapeutics Study Site 2

Boston, Massachusetts, 02114, United States

Location

Cara Therapeutics Study Site

Boston, Massachusetts, 02215, United States

Location

Cara Therapeutics Study Site

New York, New York, 10065, United States

Location

Cara Therapeutics Study Site

Nashville, Tennessee, 37232, United States

Location

Cara Therapeutics Study Site

Arlington, Texas, 76012, United States

Location

Cara Therapeutics Study Site

Newport News, Virginia, 23606, United States

Location

Cara Therapeutics Study Site

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Liver Cirrhosis, Biliary; Pruritus

Interventions

difelikefalin

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms

Study Officials

• Frédérique Menzaghi, PhD

  Cara Therapeutics

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 19, 2019
• First Posted: June 21, 2019
• Study Start: June 25, 2019
• Primary Completion: June 29, 2022
• Study Completion: June 29, 2022
• Last Updated: July 3, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)