A study to evaluate efficacy and safety of an investigational drug named volixibat in patients with itching caused by primary sclerosing cholangitis

• Register: EUCTR
• Last refreshed on: 9 January 2023
• Main ID: EUCTR2020-003027-41-DE
• Date of registration: 17/06/2021
• Prospective Registration: Yes
• Primary sponsor: Mirum Pharmaceuticals, Inc.
• Public title: A study to evaluate efficacy and safety of an investigational drug named volixibat in patients with itching caused by primary sclerosing cholangitis
• Scientific 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 (VISTAS) - VISTAS
• Date of first enrolment: 17/11/2021
• Target sample size: 300
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-003027-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Germany, Israel, United Kingdom, United States

Contacts

• Name: Mirum Clinical Lead
• Affiliation: Mirum Pharmaceuticals, Inc.

• Name: Mirum Clinical Lead
• Affiliation: Mirum Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

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

Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

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




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pruritus associated with Primary Sclerosing Cholangitis (PSC)
MedDRA version: 20.1 Level: LLT Classification code 10036732 Term: Primary sclerosing cholangitis System Organ Class: 100000004871

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: Volixibat (formely SHP626, LUM002 or SAR548304B)
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Volixibat potassium
CAS Number: 1431935-92-0
Current Sponsor code: VLX, SHP626, SHP626B (base)
Other descriptive name: VOLIXIBAT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Volixibat (formely SHP626, LUM002 or SAR548304B)
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Volixibat potassium
CAS Number: 1431935-92-0
Current Sponsor code: VLX, SHP626, SHP626B (base)
Other descriptive name: VOLIXIBAT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: 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.

Secondary Objective: 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.

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

Timepoint(s) of evaluation of this end point: Baseline from Week 12 through Week 24

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: From baseline to Week 24

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

Secondary ID(s)

NCT04663308

VLX-301

Source(s) of Monetary Support

Mirum Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 17/11/2021
Contact: