Seladelpar for Primary Biliary Cholangitis

Recruiting at 195 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Gilead Sciences

Must not be taking: Fibrates, Obeticholic acid

Disqualifiers: Cancer, Hepatitis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 60 months

500 Participants Needed

Trial Summary

What is the purpose of this trial?

An Open Label Long-Term Study to Evaluate the Safety and Tolerability of Seladelpar in Subjects with Primary Biliary Cholangitis (PBC)

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you must stop all current medications, but certain medications are prohibited. You must stop using colchicine, methotrexate, azathioprine, long-term systemic steroids, fibrates, obeticholic acid, and any experimental treatments for PBC within specific timeframes before screening. Other medications affecting liver or GI functions may also be prohibited and should be discussed with the medical monitor.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you cannot use colchicine, methotrexate, azathioprine, long-term systemic steroids, fibrates, obeticholic acid, or any experimental treatments for PBC within a few months before the trial. It's best to discuss your current medications with the trial team to see if any need to be adjusted.

What data supports the idea that Seladelpar for Primary Biliary Cholangitis is an effective drug?

The available research shows that Seladelpar is effective for treating Primary Biliary Cholangitis. In a study, patients who did not respond well to the usual treatment, ursodeoxycholic acid, showed improvement when using Seladelpar. Another study found that Seladelpar helped reduce itching, improve sleep, and decrease tiredness in patients. Additionally, a phase 3 study confirmed that Seladelpar was effective and safe compared to a placebo. Overall, these studies suggest that Seladelpar can be a beneficial option for patients who do not respond to other treatments. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Seladelpar for treating primary biliary cholangitis?

Research shows that Seladelpar, a drug that helps regulate bile acids, improved symptoms like itching and fatigue in patients with primary biliary cholangitis who did not respond well to other treatments. It also showed positive effects on liver function and was generally safe over long-term use. ^{1 2 3 4 5}

What safety data is available for Seladelpar in treating primary biliary cholangitis?

Seladelpar has been evaluated for safety in multiple clinical trials for primary biliary cholangitis (PBC). These include a phase 2 double-blind, randomized, placebo-controlled study, an open-label phase 2 study, a phase 2 open-label 52-week study, a phase 3 randomized, placebo-controlled study, and a two-year open-label extension study. These studies assessed the safety and efficacy of Seladelpar in patients with PBC, particularly those with an inadequate response or intolerance to ursodeoxycholic acid. The trials demonstrated that Seladelpar is a selective PPAR-δ agonist with anti-cholestatic, anti-inflammatory, and anti-pruritic effects, and they provided safety data over periods ranging from 3 months to 2 years. ^{1 2 3 4 5}

Is Seladelpar safe for humans?

Seladelpar has been studied in several clinical trials for primary biliary cholangitis, and these studies have evaluated its safety. The trials generally found that Seladelpar was safe for use in humans, with no major safety concerns reported. ^{1 2 3 4 5}

Is the drug Seladelpar a promising treatment for Primary Biliary Cholangitis?

Yes, Seladelpar is a promising drug for Primary Biliary Cholangitis. It has shown positive effects in improving symptoms like itching and fatigue, and it helps reduce bile acid levels in the blood. Clinical studies have demonstrated its potential to help patients who do not respond well to existing treatments. ^{1 2 3 4 6}

How is the drug Seladelpar different from other treatments for primary biliary cholangitis?

Seladelpar is unique because it is a selective PPAR-δ agonist, which helps regulate bile acid balance and has shown potent anti-cholestatic effects, improving symptoms like itching and fatigue in patients who do not respond well to the standard treatment, ursodeoxycholic acid. ^{1 2 3 4 6}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for individuals who have previously participated in a seladelpar study for Primary Biliary Cholangitis (PBC), are not pregnant or breastfeeding, and agree to use two forms of birth control. It's not open to those with certain liver conditions, kidney issues, cancer within the last 2 years, chronic viral hepatitis, or on specific medications affecting liver function.

Inclusion Criteria

You have previously participated in a study involving the drug seladelpar for PBC (primary biliary cholangitis).

I am using two forms of birth control during and 90 days after the study.

Must have given written informed consent (signed and dated)

Exclusion Criteria

My liver disease is advanced, with low albumin and high bilirubin levels.

My liver function score is 12 or higher, considering my anticoagulation medication.

I am not pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive seladelpar to evaluate long-term safety and tolerability

60 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive seladelpar for long-term evaluation

Long-term

Treatment Details

Interventions

• Seladelpar

Trial Overview The safety and tolerability of Seladelpar capsules at doses of 5 mg and 10 mg are being tested over a long term in subjects with PBC. This open-label study allows all participants to know which treatment they're receiving.

Participant Groups

Group I: Seladelpar 5 mg Capsules Experimental Treatment 1 Intervention

Group II: Seladelpar 10 mg Capsule Experimental Treatment 1 Intervention

Seladelpar is already approved in United States, European Union for the following indications:

Approved in United States as Livdelzi for:

• Primary biliary cholangitis

Approved in European Union as Livdelzi for:

• Primary biliary cholangitis

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

CymaBay Therapeutics, Inc.

Lead Sponsor

Trials

23

Recruited

3,200+

Findings from Research

In a 12-week phase 2 trial involving 41 patients with primary biliary cholangitis who did not respond adequately to ursodeoxycholic acid, seladelpar significantly reduced alkaline phosphatase levels, with a mean decrease of 53% at 50 mg and 63% at 200 mg compared to placebo.

Despite its efficacy in normalizing alkaline phosphatase levels, seladelpar was associated with grade 3 increases in liver enzymes, leading to the early termination of the study, indicating a need for further investigation at lower doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seladelpar (MBX-8025), a selective PPAR-δ agonist, in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid: a double-blind, randomised, placebo-controlled, phase 2, proof-of-concept study. Jones, D., Boudes, PF., Swain, MG., et al.[2022]

In a 1-year open-label study involving 101 patients with primary biliary cholangitis (PBC), seladelpar treatment significantly improved pruritus in 58% of patients on a lower dose and 93% on a higher dose, indicating its efficacy in alleviating this distressing symptom.

Patients also reported substantial improvements in quality of life, including reduced sleep disturbances related to itching, alongside significant biochemical changes such as reductions in serum bile acids, highlighting seladelpar's potential as an effective treatment for PBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seladelpar improved measures of pruritus, sleep, and fatigue and decreased serum bile acids in patients with primary biliary cholangitis. Kremer, AE., Mayo, MJ., Hirschfield, G., et al.[2022]

In a phase 3 study, seladelpar (10 mg) significantly improved liver biochemistry in patients with primary biliary cholangitis (PBC) who did not respond well to standard treatment, with 78.2% of patients meeting the primary efficacy endpoint compared to only 12.5% in the placebo group.

Seladelpar also effectively reduced pruritus (itching) and showed a good safety profile, with no serious treatment-related adverse events reported, indicating it is a well-tolerated option for patients with PBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study. Hirschfield, GM., Shiffman, ML., Gulamhusein, A., et al.[2023]

In a 52-week study involving adults with primary biliary cholangitis (PBC), seladelpar showed significant, dose-dependent reductions in alkaline phosphatase (ALP) levels, indicating improved liver function, with reductions of up to 41% at 8 weeks for the highest dose.

Seladelpar was found to be safe and well-tolerated, with no serious treatment-related adverse events reported, and it did not worsen pruritus (itching), a common symptom in PBC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II, randomized, open-label, 52-week study of seladelpar in patients with primary biliary cholangitis. Bowlus, CL., Galambos, MR., Aspinall, RJ., et al.[2023]

Seladelpar, a selective PPAR-δ agonist, was found to be safe for long-term use in 106 patients with primary biliary cholangitis (PBC), with no serious treatment-related adverse events reported over a 2-year period.

The treatment significantly improved biochemical markers of cholestasis and liver injury, with normalization rates of alkaline phosphatase increasing from 66% to 79% and bilirubin normalization in 43% of patients with elevated levels at baseline by the end of the second year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, clinical trial extension: Two-year safety and efficacy results of seladelpar in patients with primary biliary cholangitis. Mayo, MJ., Vierling, JM., Bowlus, CL., et al.[2023]

Seladelpar has shown significant improvements in liver biochemistry and may alleviate symptoms in patients with primary biliary cholangitis (PBC), suggesting it could be an effective treatment option.

Safety concerns regarding liver toxicity associated with seladelpar appear to have been resolved, making it a promising candidate for use as a second-line therapy in PBC compared to existing off-label fibrates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seladelpar: an investigational drug for the treatment of early-stage primary biliary cholangitis (PBC). Wetten, A., Jones, DEJ., Dyson, JK.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Seladelpar (MBX-8025), a selective PPAR-δ agonist, in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid: a double-blind, randomised, placebo-controlled, phase 2, proof-of-concept study. [2022]

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

Seladelpar improved measures of pruritus, sleep, and fatigue and decreased serum bile acids in patients with primary biliary cholangitis. [2022]

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

Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

A phase II, randomized, open-label, 52-week study of seladelpar in patients with primary biliary cholangitis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Open-label, clinical trial extension: Two-year safety and efficacy results of seladelpar in patients with primary biliary cholangitis. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Seladelpar: an investigational drug for the treatment of early-stage primary biliary cholangitis (PBC). [2023]