A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Sclerosing Cholangitis (PSC)

Study Overview
=================
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.

Official Title
-----------------
A Randomized Double-Blind Placebo-Controlled Study to Evaluate the Efficacy and Safety of Volixibat in the Treatment of Cholestatic Pruritus in Patients With Primary Sclerosing Cholangitis

Conditions
-----------------
Primary Sclerosing Cholangitis

Intervention / Treatment
-----------------
* Drug: Volixibat
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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. Subjects aged ≥12 years for eligible regions; otherwise ≥18 years Confirmed diagnosis of large duct or small duct PSC based on American Association for the Study of Liver Disease (AASLD) guidelines. Pruritus associated with PSC as assessed by Adult ItchRO. Ursodeoxycholic acid (UDCA) and anti-pruritic medication use will be allowed if meeting additional criteria. Concomitant Inflammatory Bowel Disease (IBD) is allowed if meeting additional criteria. Exclusion Criteria: Pruritus associated with an etiology other than PSC Evidence or clinical suspicion of decompensated cirrhosis, or a history of decompensation events History of ileostomy or small bowel surgery/resection or other surgeries that may have disrupted the enterohepatic circulation Evidence, history, or suspicion of other liver diseases Bile duct stent or percutaneous bile duct drain placement, or balloon dilatation procedure of a stricture within 12 weeks of Screening 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 History of liver transplantation

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Volixibat 20mg<br>Participants randomized to this arm will receive volixibat 20mg twice daily. | Drug: Volixibat<br>* Oral capsules, administered twice daily. Volixibat is an Ileal Bile Acid Transporter (IBAT) inhibitor.<br>* Other names: SHP626;|
| Experimental: Volixibat 80mg<br>Participants randomized to this arm will receive volixibat 80mg twice daily. | Drug: Volixibat<br>* Oral capsules, administered twice daily. Volixibat is an Ileal Bile Acid Transporter (IBAT) inhibitor.<br>* Other names: SHP626;|
| Placebo Comparator: Placebo<br>Participants in this arm will receive capsules matched to the study drug minus the active volixibat substance, twice daily. | Drug: Placebo<br>* Capsules matched to study drug minus active substance<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in the daily itch scores using the Adult Itch Reported Outcome (Adult ItchRO) questionnaire | The Adult ItchRO is an 11-point NRS measurement of itch severity ranging from 0=no itch to 10=worst possible itch. | Baseline through to Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 fasting serum bile acid levels |  | Baseline through to Week 28 | 
| Changes in alanine transaminase |  | Baseline through to Week 28 | 
| Changes in aspartate transaminase |  | Baseline through to Week 28 | 
| Changes in alkaline phosphatase |  | Baseline through to Week 28 | 
| Changes in 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 | 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. | Baseline through to Week 28 | 
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS®) sleep disturbance questionnaire | 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. | Baseline through to Week 28 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PSC, Pruritus, Itch, Itching, Cholestasis