|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Cholestatic Pruritus in Patients with Primary Biliary Cholangitis (PBC)
|Medical condition in easily understood language
|Itching in patients with Primary Biliary Cholangitis (PBC)
|Diseases [C] - Digestive System Diseases [C06]
|E.1.2 Medical condition or disease under investigation
|Primary biliary cholangitis
|System Organ Class
|10019805 - Hepatobiliary disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To evaluate the efficacy of volixibat versus placebo for the treatment of pruritus in participants with PBC as measured by the change in the Adult ItchRO tool in participants with PBC
|Secondary objectives of the trial
|- To evaluate the efficacy of volixibat versus placebo for the treatment of pruritus in participants with PBC using additional measures of pruritus efficacy.
- To evaluate safety and tolerability of volixibat versus placebo in participants with PBC-associated pruritus.
- To assess volixibat pharmacodynamics.
- To evaluate Quality of Life in participants with PBC-associated pruritus treated with volixibat versus placebo.
|Trial contains a sub-study
|Principal inclusion criteria
|1. Provide signed informed consent at the screening visit as well as comply with all study visits and requirements through the end of the study.
2. Male or female, age ≥18 years at the screening visit.
3. Confirmed diagnosis of PBC in line with the AASLD guidelines.
4. UDCA and anti-pruritic medication use will be allowed if meeting additional criteria.
5. Qualified pruritus associated with PBC as assessed by Adult ItchRO.
|Principal exclusion criteria
|1. Pruritus associated with an etiology other than PBC.
2. Evidence or clinical suspicion of decompensated cirrhosis or a history of decompensation events.
3. Current symptomatic cholelithiasis or inflammatory gallbladder disease.
4. History of small bowel surgery/resection impacting the terminal ileum that may disrupt the enterohepatic circulation.
5. Evidence, history, or suspicion of other liver diseases.
|E.5 End points
|Primary end point(s)
|Mean change in Adult ItchRO score comparing baseline with the average of the weekly averaged daily itch scores from Week 16 to end of double-blind study treatment
|Timepoint(s) of evaluation of this end point
|Baseline and Week 16 to end of double-blind study treatment
|Secondary end point(s)
|- Proportion of participants achieving a reduction of at least 2 points in the weekly averaged daily Adult ItchRO score from baseline to the end of double-blind study treatment
- Proportion of participants with relative reductions from baseline in the weekly averaged daily Adult ItchRO score at end of double-blind study treatment of:
- Mean number of days for each participant with daily Adult ItchRO score at least 2 points lower than the baseline score from baseline to end of double-blind study treatment
- Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), events of clinical interest (ECIs), and AEs that lead to discontinuation of study drug
- Incidence of clinically relevant laboratory abnormalities
- Changes in liver enzymes (ALT, AST, ALP, total bilirubin, and direct bilirubin)
- Changes in fasting sBA
- Change in Primary Biliary Cholangitis Quality of Life Measure (PBC-40) from baseline to end of double-blind study treatment
- Change in Patient-Reported Outcomes Measurement Information System (PROMIS®) fatigue score from baseline to end of double-blind study treatment
- Change in PROMIS sleep score from baseline to end of double-blind study treatment
|Timepoint(s) of evaluation of this end point
|Baseline and end of double-blind study treatment
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days