Volixibat for Primary Biliary Cholangitis

(VANTAGE Trial)

Recruiting at 115 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mirum Pharmaceuticals, Inc.

Disqualifiers: Decompensated cirrhosis, Cholelithiasis, Liver transplantation, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 weeks

260 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called volixibat for individuals with Primary Biliary Cholangitis (PBC) who experience severe itching. Researchers aim to determine if volixibat can reduce itching and potentially slow PBC progression. Participants will be randomly assigned to receive either a low dose or a high dose of volixibat, or a placebo (a pill with no active ingredients). The trial seeks individuals diagnosed with PBC who experience significant itching. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial allows the use of UDCA (a medication for liver disease) 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 volixibat is likely to be safe for humans?

Research has shown that volixibat has been tested in earlier studies with encouraging safety results. In studies on primary biliary cholangitis (PBC), volixibat did not cause any new safety concerns, as no unexpected side effects were reported.

Another study with adults who have nonalcoholic conditions found volixibat to be safe and tolerable. Participants did not experience any serious side effects that would question its safety.

Overall, current evidence suggests that volixibat is generally well-tolerated in people, with no major safety issues reported so far. However, as with any treatment, individual reactions can vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PBC?

Most treatments for Primary Biliary Cholangitis (PBC), like ursodeoxycholic acid and obeticholic acid, aim to improve bile flow or reduce liver inflammation. But volixibat works differently, targeting the ileal bile acid transporter (IBAT) to reduce bile acid reabsorption in the intestine. This unique mechanism could potentially lower the toxic levels of bile acids in the liver more effectively. Researchers are excited because volixibat might offer a new way to manage PBC symptoms and slow disease progression, especially for patients who don't respond well to current options.

What evidence suggests that volixibat might be an effective treatment for pruritus associated with Primary Biliary Cholangitis?

Studies have shown that volixibat can greatly reduce itching and tiredness in people with primary biliary cholangitis (PBC). Research indicates that patients experienced relief from itching early in the treatment. The improvements were significant, suggesting they were not due to chance. Additionally, there were clear reductions in the tiredness associated with PBC. These findings suggest that volixibat could effectively treat symptoms of this condition. Participants in this trial will receive either volixibat at different dosages or a placebo to further evaluate its effectiveness. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with itching due to Primary Biliary Cholangitis (PBC), as per AASLD guidelines. Participants must sign a consent form and follow study procedures. Those on UDCA or anti-itch meds can join if they meet extra rules. People with certain bowel surgeries, other liver diseases, non-PBC related itching, or severe cirrhosis cannot participate.

Inclusion Criteria

Provide signed informed consent at the screening visit as well as comply with all study visits and requirements through the end of the study

I have itching due to primary biliary cholangitis.

I am taking UDCA and anti-itching medication.

Exclusion Criteria

I have itching not caused by primary biliary cholangitis.

I've had surgery on my small intestine that affects bile acid circulation.

I am currently experiencing symptoms of gallstones or gallbladder inflammation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive volixibat 20mg or placebo twice daily for the treatment of pruritus associated with Primary Biliary Cholangitis

28 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Volixibat

Trial Overview The study tests Volixibat's effectiveness in treating PBC-related itching and its impact on the disease's progression. Participants will either receive Volixibat or a placebo (a substance with no active drug) to compare outcomes between the two groups.

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

In a phase II study involving 197 adults with non-alcoholic steatohepatitis (NASH), volixibat did not demonstrate efficacy in reducing liver fat or improving liver injury, leading to the study's termination due to lack of effectiveness.

While volixibat increased a biomarker for bile acid synthesis and decreased cholesterol levels, the treatment did not provide any therapeutic benefits for liver health, and the side effects were generally mild, with diarrhea being the most common.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Volixibat in adults with non-alcoholic steatohepatitis: 24-week interim analysis from a randomized, phase II study. Newsome, PN., Palmer, M., Freilich, B., et al.[2021]

In a phase 1 study involving 8 healthy men, volixibat was found to be minimally absorbed after oral administration, with 92.3% of the drug excreted unchanged in feces, indicating a low systemic exposure.

The study reported that adverse events were mostly mild and gastrointestinal, with no significant changes in laboratory values, suggesting that volixibat has a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absorption, Distribution, Metabolism, and Excretion of [14C]-Volixibat in Healthy Men: Phase 1 Open-Label Study. Siebers, N., Palmer, M., Silberg, DG., et al.[2018]

Combining ursodeoxycholic acid (UDCA) with bezafibrate significantly improves liver biochemistry markers in patients with primary biliary cholangitis (PBC) who do not respond adequately to UDCA alone, based on a meta-analysis of 10 trials involving 369 patients.

The combination therapy effectively reduces levels of alanine aminotransferase, alkaline phosphatase, and other liver-related markers without increasing the risk of adverse effects compared to UDCA monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of bezafibrate and ursodeoxycholic acid in patients with primary biliary cholangitis: a meta-analysis of randomized controlled trials. Agrawal, R., Majeed, M., Attar, BM., et al.[2022]

In a study involving 84 overweight and obese adults, volixibat was found to be safe and well-tolerated at doses up to 80 mg per day, with no serious adverse events reported.

Volixibat significantly increased fecal bile acid excretion and reduced total and low-density lipoprotein cholesterol levels, indicating its potential efficacy in promoting bile acid synthesis and addressing issues related to non-alcoholic steatohepatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised, double-blind, placebo-controlled phase 1 study of the safety, tolerability and pharmacodynamics of volixibat in overweight and obese but otherwise healthy adults: implications for treatment of non-alcoholic steatohepatitis. Palmer, M., Jennings, L., Silberg, DG., et al.[2019]

Current treatments for primary biliary cholangitis, such as ursodeoxycholic acid and obeticholic acid, are not effective for all patients, highlighting the need for new therapies.

The review discusses various promising drug candidates in development that target different biological pathways, including the farnesoid X receptor and immunological agents, which may offer new options for managing this autoimmune disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Work in Progress: Drugs in Development. Webb, GJ., Hirschfield, GM.[2019]

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]

The multicentric observational study compared the effects of obeticholic acid and fibrates in patients with primary biliary cholangitis, highlighting their efficacy in managing this liver disease.

Results indicated that obeticholic acid may provide superior benefits in improving liver function tests compared to fibrates, suggesting it could be a more effective treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuing Medical Education Questions: November 2021. Richter, SJ.[2023]

The prevalence of primary biliary cholangitis (PBC) in Eastern Slovakia increased from 10.2 to 14.9 cases per 100,000 inhabitants over five years, with a significant majority of patients being female (95.7%).

A majority of patients (72.1%) responded positively to treatment with ursodeoxycholic acid (UDCA), although those with higher alkaline phosphatase levels, liver cirrhosis, or younger women had poorer responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidemiology and clinical course of primary biliary cholangitis in Eastern Slovakia. Drazilova, S., Babinska, I., Gazda, J., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05050136

NCT05050136 | 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 Biliary Cholangitis (VANTAGE).

2. mirumpharma.com mirumpharma.com/wp-content/uploads/2025/05/Heneghan-M-EASL-2025-VANTAGE-28-week-data-with-volixibat-in-PBC.pdf

Volixibat for the Treatment of Cholestatic Pruritus in ... ... Outcome; PBC, primary biliary cholangitis; sBA, serum bile acid. Given the similar results between volixibat doses, the 20 mg BID dose was selected for Part ...

3. rarediseaseadvisor.com rarediseaseadvisor.com/news/volixibat-reduce-fatigue-patients-pbc/

Volixibat Could Reduce Fatigue in Patients With PBC Treatment with volixibat resulted in early and significant reductions in cholestatic pruritus and fatigue associated with primary biliary cholangitis (PBC)

4. 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.

5. 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.

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/wp-content/uploads/2024/11/Kowdley-K-AASLD-2024-VLX-For-Cholestatic-Pruritus-In-PBC.pdf

Volixibat for Cholestatic Pruritus in Primary Biliary Cholangitis Numerically greater reductions in sBA were observed with volixibat treatment compared with placebo. • No new safety signals were identified with.

8. 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 ...

9. pharmacytimes.com pharmacytimes.com/view/fda-grants-breakthrough-therapy-deignation-for-volixibat-in-cholestatic-pruritus-from-primary-biliary-cholangitis

FDA Grants Breakthrough Therapy Designation for ... FDA Grants Breakthrough Therapy Designation for Volixibat in Cholestatic Pruritus From Primary Biliary Cholangitis · 1. Mirum Pharmaceuticals.