E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pruritus associated with Primary Sclerosing Cholangitis (PSC) |
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E.1.1.1 | Medical condition in easily understood language |
Itching in patients with primary sclerosing cholangitis |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036732 |
E.1.2 | Term | Primary sclerosing cholangitis |
E.1.2 | System Organ Class | 100000004871 |
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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 as measured by the change in the Adult ItchRO tool in participants with PSC. |
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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 PSC using additional measures of pruritus efficacy.
To evaluate safety and tolerability of volixibat versus placebo in participants with PSC-associated pruritus.
To assess volixibat pharmacodynamics.
To evaluate quality of life in participants with PSC-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 |
For screening: 1. Provide freely signed informed consent and be willing to comply with all study visits and requirements through the end of the long-term extension period. 2. Age ≥16 years for eligible regions; otherwise ≥18 years 3. Confirmed diagnosis of large duct or small duct PSC based on AASLD guidelines. 4. Qualified pruritus associated with PSC as assessed by Adult ItchRO 5. Completion of ≥80% of daily Adult ItchRO assessments during the screening period 6. UDCA and anti-pruritic medication use will be allowed if meeting additional criteria. Concomitant IBD is allowed if meeting additional criteria 7. Participants with AIH who are on stable treatment with medications
For randomization 1. Completion of ≥80% of Adult ItchRO assessments during the single-blind, placebo run- in period 2. Study drug compliance of ≥80% during the single-blind, placebo run-in period
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E.4 | Principal 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. Presumptive or diagnosed ascending cholangitis within 12 weeks of screening through Day 1 4. Placement of a percutaneous drain or biliary stent within 12 weeks of screening through Day 1 5. Balloon dilatation procedure of a stricture within 12 weeks of screening through Day 1 6. History of ileostomy or small bowel surgery/resection or other surgeries that may have disrupted the enterohepatic circulation 7. ECG with clinically significant abnormalities as determined by the investigator 8. Evidence, history, or suspicion of other liver and GI-related diseases and malignancies 9. Positive for HIV antibody 10. Any active infection that, in the opinion of the investigator or medical monitor, would preclude successful participation in the study 11. Unstable and/or serious medical disease that is likely to impair the participant’s ability to participate in all aspects of the study, confound efficacy and/or safety assessments, or result in substantially shortened life expectancy 12. Clinically relevant alcohol use disorder or drug abuse within 24 weeks of screening
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change in the Adult ItchRO comparing baseline with the average of the weekly averaged worst daily itch scores from Week 12 through Week 24 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline from Week 12 through Week 24 |
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E.5.2 | Secondary end point(s) |
o Proportion of participants achieving a reduction of at least 2 points in the weekly averaged worst daily itch Adult ItchRO score from baseline to Week 24 o Proportion of participants with a weekly averaged worst daily itch Adult ItchRO score of <4 at Week 24 o Proportion of participants with relative reductions from baseline in the weekly averaged worst daily itch Adult ItchRO score at Week 24 of: ≥30% ≥50% o Mean number of days for each participant with worst daily itch Adult ItchRO score at least 2 points lower than the baseline mean daily score from baseline to Week 24 o Mean number of days for each participant with worst daily itch Adult ItchRO score of <4 from baseline to Week 24 o To evaluate safety and tolerability of volixibat versus placebo in participants with PSC associated pruritus on the basis of the following endpoints: • Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), events of clinical interest (ECIs), and adverse events (AEs) that lead to discontinuation of study treatment • Incidence of clinically relevant laboratory abnormalities • Incidence of gastrointestinal (GI) symptoms as measured by partial Mayo IBD score in participants with IBD o To assess volixibat pharmacodynamics on the basis of the following endpoints: • Changes in liver enzymes (ALT, AST, ALP, total bilirubin, and direct bilirubin) • Changes in fasting serum bile acid (sBA) levels o To evaluate quality of lifeQoL in participants with PSC-associated pruritus treated with volixibat versus placebo on the basis of the following endpoints: • Change in Primary Sclerosing Cholangitis Specific Patient-Reported Outcomes (PSC PRO) from baseline to Week 24 • Change in PROMIS® fatigue score from baseline to Week 24 • Change in PROMIS sleep score from baseline to Week 24
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 |
Israel |
United States |
Germany |
United Kingdom |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
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 |