Volixibat for Itching in Primary Sclerosing Cholangitis

(VISTAS Trial)

Not currently recruiting at 121 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medication, volixibat, to reduce itching associated with Primary Sclerosing Cholangitis (PSC), a liver condition. Researchers aim to determine if volixibat can ease itching and slow disease progression. Participants will receive either varying doses of volixibat or a placebo (a pill with no active medicine). Individuals with a confirmed PSC diagnosis and persistent itching may be suitable for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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 suggesting that this trial's treatments are likely to be safe?

Research shows that volixibat is under study to assess its safety and tolerability. Earlier studies have found that volixibat is generally safe for adults, with most people tolerating it well. Research on conditions like nonalcoholic fatty liver disease suggests that participants taking volixibat did not experience serious side effects. However, like any medication, some individuals might encounter mild side effects, such as digestive issues, though serious problems appear rare.

Volixibat has also been tested for other conditions, enhancing researchers' understanding of its safety. Since this study is in an early phase, it represents a step toward determining volixibat's safety for treating itching caused by primary sclerosing cholangitis (PSC). Overall, current data suggests that volixibat has a promising safety profile, but further testing is needed to confirm this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for itching in PSC?

Volixibat is unique because it targets bile acid transport to alleviate itching in primary sclerosing cholangitis (PSC), a condition where current treatments primarily focus on managing symptoms rather than addressing underlying causes. Most treatments for PSC, like ursodeoxycholic acid, aim at liver protection but do not effectively reduce itching. Volixibat works differently by inhibiting the ileal bile acid transporter (IBAT), which may help decrease bile acid levels and relieve itching more directly. Researchers are excited about this treatment as it offers a novel approach with the potential for quicker, more targeted relief for individuals suffering from this challenging symptom.

What evidence suggests that volixibat could be an effective treatment for itching in Primary Sclerosing Cholangitis?

Research has shown that volixibat may help reduce itching in people with primary sclerosing cholangitis (PSC). Studies have found that volixibat lowers bile acid levels in the blood, which can relieve itching. Data from a similar study on primary biliary cholangitis, a related liver condition, showed significant improvements in itching with volixibat treatment. This trial will evaluate different dosages of volixibat, with some participants receiving 20mg and others 80mg, to determine its effectiveness in reducing itchiness in PSC patients. Initial findings are promising, but more research is needed to confirm these results. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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]

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 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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04663308

NCT04663308 | A Study to Evaluate Efficacy and Safety of ... A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Sclerosing Cholangitis (PSC) ( ...

2. crohnscolitisfoundation.org crohnscolitisfoundation.org/a-study-to-evaluate-efficacy-and-safety-of-investigational-drug-named-volixibat-patients-with

A Study to Evaluate Efficacy and Safety of ... As a result, volixibat treatment is expected to lower bile acid levels in the blood which in turn may help ease itch experienced by people with ...

3. liverdiseasenews.com liverdiseasenews.com/news/phase-2-trial-volixibat-psc-now-fully-enrolled/

Phase 2 trial of volixibat for PSC-related itching now fully ... A Phase 2 trial testing volixibat for the treatment of itching in people with primary sclerosing cholangitis is fully enrolled.

4. biospace.com biospace.com/press-releases/volixibat-data-from-mirums-vantage-pbc-study-showcased-at-easl

Volixibat Data from Mirum's VANTAGE PBC Study ... 28-week data from the Phase 2b VANTAGE PBC study highlights statistically significant improvements in pruritus and numeric improvements in ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/61/NCT04718961/Prot_000.pdf

PROTOCOL NUMBER: VLX-401 The secondary efficacy endpoints are designed to evaluate the efficacy of volixibat versus placebo for the treatment of pruritus in participants with ICP as ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02787304

Study Details | NCT02787304 | Volixibat (SHP626) in the ... The purpose of this study is to determine if the investigational treatment volixibat (SHP626) is safe, tolerable and effective in adults with nonalcoholic ...

7. mirumpharma.com mirumpharma.com/our-science/pipeline/

Our Discoveries - Mirum Pharma Primary Sclerosing Cholangitis (PSC) Phase 2b VISTAS Study. Evaluating efficacy and safety of volixibat in patients with itching caused by PSC. View full ...

8. firstwordpharma.com firstwordpharma.com/story/5959323

Volixibat Data from Mirum's VANTAGE PBC Study ... 28-week data from the Phase 2b VANTAGE PBC study highlights statistically significant improvements in pruritus and numeric improvements in fatigue.