Clinical trial NCT03995212: Study to Evaluate the Safety and Efficacy of Oral CR845 (Difelikefalin) in Patients With Primary Biliary Cholangitis (PBC) and Moderate-to-Severe Pruritus
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cholestatic Pruritus
Keywords: Primary Biliary Cholangitis
Pruritus
CR845
Chronic Itch
difelikefalin
Itch
Itching
Generalized pruritus
Lead sponsor: Cara Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-06-21
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Baseline, Week 16
Secondary outcomes:
measure: Improvement in itch-related quality of life as assessed by the change from baseline to Week 16 in total Skindex-10 Scale score
timeFrame: Baseline, Week 16
measure: Improvement in itch-related quality of life as assessed by the change from baseline to Week 16 in 5-D Itch Scale score
timeFrame: Baseline, Week 16
measure: 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
timeFrame: Week 16
Other outcomes:
Locations:
city: Coronado
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Rialto
country: United States
facility: Cara Therapeutics Study Site
state: California
city: San Francisco
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Colorado Springs
country: United States
facility: Cara Therapeutics Study Site
state: Colorado
city: Miami
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Plantation
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Indianapolis
country: United States
facility: Cara Therapeutics Study Site
state: Indiana
city: Boston
country: United States
facility: Cara Therapeutics Study Site 2
state: Massachusetts
city: Boston
country: United States
facility: Cara Therapeutics Study Site
state: Massachusetts
city: New York
country: United States
facility: Cara Therapeutics Study Site
state: New York
city: Nashville
country: United States
facility: Cara Therapeutics Study Site
state: Tennessee
city: Arlington
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Newport News
country: United States
facility: Cara Therapeutics Study Site
state: Virginia
city: Morgantown
country: United States
facility: Cara Therapeutics Study Site
state: West Virginia
Study officials:
affiliation: Cara Therapeutics
name: Frédérique Menzaghi, PhD
role: STUDY_DIRECTOR
References: