Volixibat for Primary Biliary Cholangitis

(VANTAGE Trial)

Recruiting at 87 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

180 Participants Needed

Trial Summary

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 Volixibat safe for humans?

Volixibat has been studied for safety in humans, including healthy men and adults with non-alcoholic steatohepatitis. These studies looked at how the body absorbs, processes, and gets rid of the drug, and they found it to be generally safe and well-tolerated. ^{1 2 3 4 5}

How is the drug Volixibat different from other drugs for primary biliary cholangitis?

Volixibat is unique because it works as a bile acid reuptake inhibitor, which is different from the commonly used drugs like ursodeoxycholic acid and obeticholic acid that target other pathways. This novel mechanism may offer an alternative for patients who do not respond well to existing treatments. ^{2 3 6 7 8}

What is the purpose of this trial?

This trial is testing a medicine called volixibat that may help reduce itching in people with a liver disease that often causes severe itching. Volixibat works by blocking certain chemicals in the body that cause itching. The study also aims to see if the medicine can slow down the progression of the liver disease.

Eligibility Criteria

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

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

Treatment Details

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.

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 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]

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]

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]

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]

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]

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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

Absorption, Distribution, Metabolism, and Excretion of [14C]-Volixibat in Healthy Men: Phase 1 Open-Label Study. [2018]

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

Work in Progress: Drugs in Development. [2019]

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

Continuing Medical Education Questions: November 2021. [2023]

4. England 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. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Volixibat in adults with non-alcoholic steatohepatitis: 24-week interim analysis from a randomized, phase II study. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Epidemiology and clinical course of primary biliary cholangitis in Eastern Slovakia. [2020]

7. 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]

8. Greece pubmed.ncbi.nlm.nih.gov

Effectiveness of bezafibrate and ursodeoxycholic acid in patients with primary biliary cholangitis: a meta-analysis of randomized controlled trials. [2022]