Primary Sclerosing Cholangitis
Conditions
Keywords
Pruritus, PSC, Itch, Itching, Cholestasis
Brief summary
The purpose of this clinical research study is to learn more about the use of the study medicine, volixibat, for the treatment of pruritus (itching) associated with Primary Sclerosing Cholangitis (PSC), and to assess the possible impact on the disease progression of PSC.
Interventions
DRUGVolixibat
Oral capsules, administered twice daily. Volixibat is an Ileal Bile Acid Transporter (IBAT) inhibitor.
DRUGPlacebo
Capsules matched to study drug minus active substance
Sponsors
Mirum Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provide freely signed informed consent and assent (as applicable) and be willing to comply with all study visits and requirements through end of study, including the follow-up period. 2. Subjects aged ≥12 years for eligible regions; otherwise ≥18 years 3. Confirmed diagnosis of large duct or small duct PSC based on American Association for the Study of Liver Disease (AASLD) guidelines. 4. Pruritus associated with PSC as assessed by Adult ItchRO. 5. Ursodeoxycholic acid (UDCA) and anti-pruritic medication use will be allowed if meeting additional criteria. 6. Concomitant Inflammatory Bowel Disease (IBD) is allowed if meeting additional criteria.
Exclusion criteria
1. Pruritus associated with an etiology other than PSC 2. Evidence or clinical suspicion of decompensated cirrhosis, or a history of decompensation events 3. History of ileostomy or small bowel surgery/resection or other surgeries that may have disrupted the enterohepatic circulation 4. Evidence, history, or suspicion of other liver disease; PSC patients with AIH are not excluded. 5. Bile duct stent or percutaneous bile duct drain placement, or balloon dilatation procedure of a stricture within 12 weeks of Screening 6. Exceeding pre-defined biochemical values for alanine aminotransferase/aspartate aminotransferase (ALT/AST), estimated glomerular filtration rate (eGFR),serum creatinine (sCr), platelet count, international normalized ratio (INR) and total bilirubin 7. History of liver transplantation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean change in the daily itch scores using the Adult Itch Reported Outcome (Adult ItchRO) questionnaire | Baseline through to Week 28 | The Adult ItchRO is an 11-point NRS measurement of itch severity ranging from 0=no itch to 10=worst possible itch. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with itch response using the Adult ItchRO | Baseline through to Week 28 | — |
| The incidence of adverse events | Baseline through to Week 28 | — |
| Changes in serum bile acid levels | Baseline through to Week 28 | — |
| Changes in alkaline phosphatase | Baseline through to Week 28 | — |
| Changes in total bilirubin levels | Baseline through to Week 28 | — |
| Change in Primary Sclerosing Cholangitis-Specific Patient-Reported Outcome | Baseline through to Week 28 | — |
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS®) fatigue questionnaire | Baseline through to Week 28 | The PROMIS® Fatigue questionnaire is a 5-point response scale. Respondents endorse each item using a 5-point response scale: Never, Rarely, Sometimes, Often, and Always. |
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS®) sleep disturbance questionnaire | Baseline through to Week 28 | The PROMIS® Sleep Disturbance in an 8-item measure that assesses quality of sleep, sleep depth, and restoration associated with sleep. It is a 5-point response scale, the specific response options vary by items. The first 4 items use response options that range from Not at all to Very much. The next 3 items use response options that range from Never to Always. The final item assesses sleep quality ranging from Very poor to Very good. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, France, Germany, Israel, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States
Outcome results
None listed