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

Study Overview
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Brief Summary
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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 Biliary Cholangitis (PBC), and to assess the possible impact on the disease progression of PBC.

Official Title
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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 Biliary Cholangitis

Conditions
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Primary Biliary Cholangitis, PBC

Intervention / Treatment
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* Drug: Volixibat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide signed informed consent at the screening visit as well as comply with all study visits and requirements through the end of the study Male or female, age ≥18 years at the screening visit Confirmed diagnosis of PBC in line with the AASLD guidelines UDCA and anti-pruritic medication use will be allowed if meeting additional criteria Qualified pruritus associated with PBC as assessed by Adult ItchRO Exclusion Criteria: Pruritus associated with an etiology other than PBC Evidence or clinical suspicion of decompensated cirrhosis or a history of decompensation events Current symptomatic cholelithiasis or inflammatory gallbladder disease History of small bowel surgery/resection impacting the terminal ileum that may disrupt the enterohepatic circulation. Evidence, history, or suspicion of other liver diseases

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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 without the active pharmaceutical ingredient<br>|

What is the study measuring?
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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 to week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with itch response using the Adult ItchRO |  | Baseline to week 28 | 
| Incidence of adverse events |  | Baseline to week 28 | 
| Changes in alkaline phosphatase |  | Baseline to week 28 | 
| Changes in total bilirubin |  | Baseline to week 28 | 
| Changes in serum bile acid levels |  | Baseline to week 28 | 
| Change in Primary Biliary Cholangitis Quality of Life Measure (PBC-40) | PBC-40 questionnaire is scored on a scale of 40 to 200, with higher scores indicating poorer quality of life | Baseline 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 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 to week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pruritus, PBC, Primary Biliary Cholangitis, Hepatobiliary disorders, Itching, Cholangitis