Volixibat for Itching in Primary Sclerosing Cholangitis

(VISTAS Trial)

Recruiting at 93 trial locations

Overseen By Kidist Yimam, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Mirum Pharmaceuticals, Inc.

Disqualifiers: Decompensated cirrhosis, Ileostomy, Other liver disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 28 weeks

200 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this clinical research study is to learn more about the use of the study medicine, volixibat, for the treatment of pruritus (itching) associated with Primary Sclerosing Cholangitis (PSC), and to assess the possible impact on the disease progression of PSC.

Will I have to stop taking my current medications?

The trial allows the use of ursodeoxycholic acid (UDCA) and anti-itch medications if certain criteria are met, so you may not need to stop these medications. However, the protocol does not specify about other medications.

Is there any evidence that the drug Volixibat is effective for treating itching in primary sclerosing cholangitis?

Research on similar drugs, like GSK2330672 and linerixibat, which are also bile acid transporter inhibitors, shows they can help reduce itching in related liver conditions like primary biliary cholangitis. This suggests that Volixibat might also be effective for itching in primary sclerosing cholangitis. ^{1 2 3 4 5}

Is Volixibat safe for humans?

There is no specific safety data available for Volixibat in the provided research articles. ^{1 2 4 6 7}

How is the drug Volixibat different from other treatments for itching in primary sclerosing cholangitis?

Volixibat is unique because it works by inhibiting the ileal bile acid transporter, which reduces the re-absorption of bile acids in the gut, potentially lowering their levels in the body and alleviating itching. This mechanism is similar to other drugs like linerixibat and maralixibat, but Volixibat is specifically being studied for its effects in primary sclerosing cholangitis, a condition with limited treatment options for itching. ^{1 2 4 6 8}

Eligibility Criteria

This trial is for individuals aged ≥16 with Primary Sclerosing Cholangitis (PSC) who experience itching. They must understand the study and agree to its requirements, including follow-up visits. Participants can have Inflammatory Bowel Disease if they meet certain conditions and may use specific medications for PSC-related itching.

Inclusion Criteria

I have been diagnosed with PSC following AASLD guidelines.

I have IBD but meet specific criteria for this trial.

I am 16 years old or older.

Exclusion Criteria

I have or might have liver disease.

I had a procedure for bile duct blockage within the last 12 weeks.

I have or might have severe liver damage or have had liver failure events.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive volixibat or placebo twice daily to evaluate efficacy and safety in treating pruritus associated with PSC

28 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Volixibat

Trial Overview The study is testing Volixibat's effectiveness in treating itchiness caused by PSC and its potential impact on the disease's progression. Participants will be randomly assigned to receive either Volixibat or a placebo (a substance with no therapeutic effect).

Participant Groups

Group I: Part 2 Arm 1: Volixibat Selected Dose 20mg Experimental Treatment 1 Intervention

Participants randomized to this arm will receive volixibat 20mg twice daily.

Group II: Part 1 Arm 2: Volixibat 80mg Experimental Treatment 1 Intervention

Participants randomized to this arm will receive volixibat 80mg twice daily.

Group III: Part 1 Arm 1: Volixibat 20mg Experimental Treatment 1 Intervention

Participants randomized to this arm will receive volixibat 20mg twice daily.

Group IV: Part 1 Arm 3: Placebo Placebo Group 1 Intervention

Participants in this arm will receive capsules matched to the study drug minus the active volixibat substance, twice daily.

Group V: Part 2 Arm 2: Placebo Placebo Group 1 Intervention

Participants in this arm will receive capsules matched to the study drug minus the active volixibat substance, twice daily.

Who Is Running the Clinical Trial?

Mirum Pharmaceuticals, Inc.

Lead Sponsor

Trials

32

Recruited

102,000+

Findings from Research

In a phase 2a trial involving 22 patients with primary biliary cholangitis, the drug GSK2330672 was found to be safe and effective in significantly reducing pruritus (itch) severity over 14 days, with a 57% reduction in itch scores on a numerical rating scale.

While GSK2330672 showed promising results in alleviating itch and reducing serum bile acids, the most common side effect was diarrhea, which could limit its long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of ileal bile acid transporter inhibitor GSK2330672 on pruritus in primary biliary cholangitis: a double-blind, randomised, placebo-controlled, crossover, phase 2a study. Hegade, VS., Kendrick, SF., Dobbins, RL., et al.[2022]

In the Phase 2b GLIMMER study involving 147 adults with primary biliary cholangitis and moderate-to-severe itching, linerixibat showed a dose-dependent reduction in itch scores, particularly at higher doses, although the primary analysis did not show significant differences from placebo.

Diarrhea was the most common side effect associated with linerixibat, and its incidence increased with the dose, indicating a need for careful dose management in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLIMMER: A Randomized Phase 2b Dose-Ranging Trial of Linerixibat in Primary Biliary Cholangitis Patients With Pruritus. Levy, C., Kendrick, S., Bowlus, CL., et al.[2023]

In a study involving 44 patients with primary biliary cholangitis (PBC) suffering from moderate to severe pruritus, nalfurafine hydrochloride significantly reduced itch severity after 12 weeks of treatment, as shown by a decrease in both PBC-40 itch scores and visual analog scale (VAS) scores.

While nalfurafine effectively alleviated pruritus, it did not significantly improve overall health-related quality of life (HRQOL) measures, indicating that while it helps with itching, it may not address other quality of life issues in PBC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is patient-reported outcome improved by nalfurafine hydrochloride in patients with primary biliary cholangitis and refractory pruritus? A post-marketing, single-arm, prospective study. Yagi, M., Tanaka, A., Namisaki, T., et al.[2019]

In a systematic review of 23 randomized controlled trials involving 2,194 patients, UDCA, methotrexate, and GSK2330672 were found to significantly relieve itching in patients with primary biliary cholangitis (PBC).

While these treatments showed promise for itching relief, the evidence for their effects on improving serum alkaline phosphatase (ALP) or γ-glutamyl transpeptidase (γ-GGT) levels was inconclusive due to high variability among studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pharmacological interventions for pruritus in primary biliary cholangitis: A systematic review and meta-analysis. Xu, C., Yue, R., Lv, X., et al.[2022]

In a study of 24 adults with primary sclerosing cholangitis (PSC), treatment with cenicriviroc (CVC) resulted in a modest median reduction of 18% in alkaline phosphatase (ALP) levels after 24 weeks, indicating some potential efficacy.

CVC was generally well tolerated, with 83.3% of participants reporting mild to moderate adverse events, such as rash and fatigue, and no new safety concerns were identified during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Cenicriviroc in Patients With Primary Sclerosing Cholangitis: PERSEUS Study. Eksteen, B., Bowlus, CL., Montano-Loza, AJ., et al.[2023]

Linerixibat, a selective inhibitor of the ileal bile acid transporter, effectively reduces cholestatic pruritus in patients with primary biliary cholangitis (PBC) by lowering serum bile acids, as demonstrated in the phase IIb GLIMMER trial.

The study found a dose-dependent relationship where higher doses of linerixibat increased the number of patients experiencing significant itch relief, but also raised the likelihood of diarrhea, leading to the selection of a 40 mg twice-daily dose for further testing in the phase III GLISTEN trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Dose-Response-Time Analysis of Itch Reduction and Patient-Reported Tolerability Supports Phase III Dose Selection for Linerixibat. Carreño, F., Karatza, E., Mehta, R., et al.[2023]

In a double-blind, randomized, placebo-controlled trial involving 74 patients with cholestatic diseases, bezafibrate significantly reduced moderate to severe pruritus by at least 50% in 45% of participants compared to only 11% in the placebo group, indicating its efficacy in alleviating itch associated with PSC and PBC.

Bezafibrate also improved the intensity of pruritus in the morning and evening and reduced serum alkaline phosphatase levels, suggesting it may help alleviate biliary damage, although it did not significantly change serum bile acids or autotaxin activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies: A Double-Blind, Randomized, Placebo-Controlled Trial. de Vries, E., Bolier, R., Goet, J., et al.[2021]

In a 14-week open-label study involving 27 adults with primary sclerosing cholangitis (PSC), maralixibat significantly reduced serum bile acid levels by 16.7%, indicating its potential efficacy in managing bile acid-related symptoms.

Participants with severe pruritus experienced a notable improvement, with itch scores decreasing by 70% in those with the highest baseline scores, although gastrointestinal side effects were common, primarily mild to moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and efficacy of maralixibat in adults with primary sclerosing cholangitis: Open-label pilot study. Bowlus, CL., Eksteen, B., Cheung, AC., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Effect of ileal bile acid transporter inhibitor GSK2330672 on pruritus in primary biliary cholangitis: a double-blind, randomised, placebo-controlled, crossover, phase 2a study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

GLIMMER: A Randomized Phase 2b Dose-Ranging Trial of Linerixibat in Primary Biliary Cholangitis Patients With Pruritus. [2023]

3. Japan pubmed.ncbi.nlm.nih.gov

Is patient-reported outcome improved by nalfurafine hydrochloride in patients with primary biliary cholangitis and refractory pruritus? A post-marketing, single-arm, prospective study. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pharmacological interventions for pruritus in primary biliary cholangitis: A systematic review and meta-analysis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Cenicriviroc in Patients With Primary Sclerosing Cholangitis: PERSEUS Study. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Population Dose-Response-Time Analysis of Itch Reduction and Patient-Reported Tolerability Supports Phase III Dose Selection for Linerixibat. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies: A Double-Blind, Randomized, Placebo-Controlled Trial. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and efficacy of maralixibat in adults with primary sclerosing cholangitis: Open-label pilot study. [2023]