IRB Study Number 22-661
Status Recruiting
Phase Phase 2
Locations Cleveland Clinic Weston Hospital , Cleveland Clinic Main Campus
Institute Digestive Disease & Surgery Institute
Description
This is a Phase 2, randomized, double-blind, placebo-controlled study of volixibat, an oral bile acid transporter inhibitor, in adults with primary biliary cholangitis (PBC) who have bothersome itching.
The study looks at whether volixibat can safely reduce itch severity and improve quality of life, while also monitoring liver tests and other lab values.
Participants complete a screening and run-in period with daily itch diaries and, if eligible, are randomized to receive volixibat or placebo for the double-blind treatment period, with the option to continue in a long-term extension.
Inclusion Criteria
Adult, age ≥ 18 years.
Able and willing to sign informed consent and follow all study visits and procedures.
Diagnosis of primary biliary cholangitis (PBC), supported by at least two of:
History of persistently elevated alkaline phosphatase (ALP) first noted ≥ 6 months before screening.
Positive antimitochondrial antibody (AMA) or PBC-specific autoantibodies.
Liver biopsy at any time in the past consistent with PBC (nonsuppurative destructive cholangitis and bile duct loss).
If on ursodeoxycholic acid (UDCA):
On a stable dose for at least 6 weeks before screening, or
Off UDCA for at least 6 weeks and considered clinically stable by the investigator.
Concomitant systemic therapies for PBC or cholestatic pruritus (for example: fibrates, SSRIs, rifampin, gabapentin, cholestyramine, opioid-receptor antagonists, and similar agents) are either:
On a stable dose for at least 6 weeks before screening, or
Discontinued for at least 2 weeks before screening.
For agents such as elafibranor or seladelpar: stable for at least 6 months or stopped for at least 3 months before screening.
Average daily Adult ItchRO score ≥ 1 during the 2 consecutive weeks leading up to the randomization visit (per protocol).
At least 70% completion of the Adult ItchRO daily diary during the same 2-week period.
Exclusion Criteria
- Chronic pruritus due to another cause that would interfere with assessing PBC-related itching.
- Evidence of decompensated cirrhosis or complications of cirrhosis, such as:
- Variceal bleeding or untreated esophageal/gastric varices.
- Ascites.
- Hepatic encephalopathy.
- Hepatorenal syndrome.
(Compensated cirrhosis with preserved liver function and no complications may be allowed per protocol.) - Current symptomatic gallstones or inflammatory gallbladder disease.
- Patients with prior cholecystectomy (≥ 3 months before screening) may be eligible.
- History of small bowel surgery or resection involving the terminal ileum (for example, ileostomy, ileo-anal pouch, or other procedures/conditions) that may disrupt enterohepatic bile acid circulation.
- Any other significant liver disease besides PBC, including, but not limited to:
- Active viral hepatitis (A, B, or C) per protocol definitions.
- Primary sclerosing cholangitis or secondary sclerosing cholangitis.
- IgG4-related cholangitis.
- Wilson disease, alpha-1 antitrypsin deficiency, or hereditary hemochromatosis.
- Suspected or confirmed cholangiocarcinoma or hepatocellular carcinoma.
- Prior liver transplantation.
- Other chronic liver conditions considered clinically significant by the investigator.
- PBC with autoimmune hepatitis overlap may be allowed only if liver tests and IgG are within protocol-specified limits (for example, ALT not markedly elevated and IgG not significantly elevated).
- Any unstable, serious medical condition (cardiac, pulmonary, renal, neurologic, or other) that, in the investigator’s opinion, could increase risk, shorten survival, or interfere with study participation or interpretation of results.
- Any other condition, including lab abnormalities or social factors, that in the investigator’s judgment makes the participant unsuitable for the study.
