E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cholestatic Pruritus in Patients with Primary Biliary Cholangitis (PBC) |
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E.1.1.1 | Medical condition in easily understood language |
Itching in patients with Primary Biliary Cholangitis (PBC) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10080429 |
E.1.2 | Term | Primary biliary cholangitis |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | 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 |
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E.2.2 | 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | 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. |
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E.4 | 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. |
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E.5 End points |
E.5.1 | 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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and Week 16 to end of double-blind study treatment |
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E.5.2 | 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: - ≥30% - ≥50% - 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline and end of double-blind study treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Germany |
Israel |
Italy |
United Kingdom |
United States |
France |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |