Slow enrollment due primarily to Covid-19

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.

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.

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.