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)
Summary description of the study
The purpose of this study is to learn more about the use of the investigational drug Volixibat in the treatment of pruritus (itching) associated with PSC. The study lasts approximately 32 weeks or at least 2 ½ years if patients participate in the long-term extension study. During this period, they will be examined at the study center up to 11 times, or 21 times or more if they participate in the long-term extension study. The study consists of 2 parts. In Part 1, two different doses of the investigational drug are compared to a placebo over a period of 28 weeks. A placebo is a capsule that looks exactly like the investigational drug but contains no active ingredient. Part 2 of the study is similar to Part 1, but only one dose of the investigational drug is compared to a placebo. Two different strengths of Volixibat capsules (5 mg and 20 mg, acid-free equivalent) and a corresponding placebo will be provided, and neither the patient nor the doctor will know which treatment the patient will receive.
(BASEC)
Intervention under investigation
• Study treatment phase: 4 capsules of the investigational drug Volixibat or placebo twice daily over a period of 28 weeks.
• Long-term extension study: All individuals who qualify for the study and choose to participate will take Volixibat twice daily for at least 2 years.
(BASEC)
Disease under investigation
Primary Sclerosing Cholangitis (PSC) and pruritus (severe itching), a common symptom of this condition. Currently, there is no effective therapy for this symptom of the disease and only limited treatment options. Therefore, the study sponsor is developing a new therapy. This study tests the investigational drug called Volixibat. The sponsor wants to find out whether the investigational drug can be used to treat itching, as well as to lower high serum bile acid levels that can harm the liver and are associated with liver diseases.
(BASEC)
- Age ≥12 years (where permitted); otherwise ≥18 years - Confirmed PSC diagnosis - Qualified pruritus associated with PSC, assessed using specific questionnaires. (BASEC)
Exclusion criteria
- Chronic itching of other causes - Evidence or clinical suspicion of decompensated cirrhosis or a clinical history of decompensation events - Suspected or diagnosed ascending cholangitis, initiation of percutaneous drainage or a bile duct stent, or balloon dilation of a stricture - ECG with clinically significant abnormalities - Other liver diseases and malignant conditions - Positive for HIV antibodies - Any active infection that would exclude successful participation in the study - Unstable and/or serious medical condition that could impair your ability to participate in all aspects of the study - Alcohol dependence or drug abuse (BASEC)
Trial sites
Zurich
(BASEC)
Sponsor
Mirum Pharmaceuticals AG Badr Fathi Baarerstrasse 22 6300 Zug
(BASEC)
Contact
Contact Person Switzerland
Badr Fathi
+41764392629
clinicaltrials@cluttermirumpharma.comMirum Pharmaceuticals AG Baarerstrasse 22 6300 Zug
(BASEC)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Zurich
(BASEC)
Date of authorisation
13.08.2024
(BASEC)
ICTRP Trial ID
NCT04663308 (ICTRP)
Official title (approved by ethics committee)
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) (BASEC)
Academic 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 (ICTRP)
Public title
A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Sclerosing Cholangitis (PSC) (ICTRP)
Disease under investigation
Primary Sclerosing Cholangitis (ICTRP)
Intervention under investigation
Drug: VolixibatDrug: Placebo (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator). (ICTRP)
Inclusion/Exclusion criteria
Inclusion Criteria:
1. Provide freely signed informed consent and assent (as applicable) and be willing to
comply with all study visits and requirements through end of study, including the
follow-up period.
2. Subjects aged =12 years for eligible regions otherwise =18 years
3. Confirmed diagnosis of large duct or small duct PSC based on American Association
for the Study of Liver Disease (AASLD) guidelines.
4. Pruritus associated with PSC as assessed by Adult ItchRO.
5. Ursodeoxycholic acid (UDCA) and anti-pruritic medication use will be allowed if
meeting additional criteria.
6. Concomitant Inflammatory Bowel Disease (IBD) is allowed if meeting additional
criteria.
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. History of ileostomy or small bowel surgery/resection or other surgeries that may
have disrupted the enterohepatic circulation
4. Evidence, history, or suspicion of other liver disease PSC patients with AIH are
not excluded.
5. Bile duct stent or percutaneous bile duct drain placement, or balloon dilatation
procedure of a stricture within 12 weeks of Screening
6. Exceeding pre-defined biochemical values for alanine aminotransferase/aspartate
aminotransferase (ALT/AST), estimated glomerular filtration rate (eGFR),serum
creatinine (sCr), platelet count, international normalized ratio (INR) and total
bilirubin
7. History of liver transplantation (ICTRP)
not available
Primary and secondary end points
Mean change in the daily itch scores using the Adult Itch Reported Outcome (Adult ItchRO) questionnaire (ICTRP)
Proportion of participants with itch response using the Adult ItchRO;The incidence of adverse events;Changes in serum bile acid levels;Changes in alkaline phosphatase;Changes in total bilirubin levels;Change in Primary Sclerosing Cholangitis-Specific Patient-Reported Outcome;Change in Patient-Reported Outcomes Measurement Information System (PROMIS�) fatigue questionnaire;Change in Patient-Reported Outcomes Measurement Information System (PROMIS�) sleep disturbance questionnaire (ICTRP)
Registration date
17.11.2020 (ICTRP)
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
Clinical Trials Mirum, Clinicaltrials@mirumpharma.com, +16506674085 (ICTRP)
Secondary trial IDs
2020-003027-41, 2023-505764-11-00, VLX-301 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/study/NCT04663308 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available