Seladelpar for Primary Biliary Cholangitis

(IDEAL Trial)

Recruiting at 73 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Gilead Sciences

Must be taking: Ursodeoxycholic acid

Must not be taking: Obeticholic acid, Fibrates

Disqualifiers: Advanced PBC, Other liver diseases, HIV, Alcohol abuse, Cancer, 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: 52 weeks

90 Participants Needed

Trial Summary

What is the purpose of this trial?

To Determine the Effects of Seladelpar on Normalization of Alkaline Phosphatase Levels in Subjects with Primary Biliary Cholangitis (PBC) and an Incomplete Response or Intolerance to Ursodeoxycholic Acid (UDCA). The primary objective is to evaluate the effect of seladelpar treatment at Week 52 compared to placebo based on normalization of alkaline phosphatase (ALP) defined by a composite endpoint of ALP ≤ 1.0× upper limit of normal (ULN) and ≥ 15% decrease from baseline in PBC participants with an ALP value greater than ULN but less than 1.67× ULN.

Will I have to stop taking my current medications?

The trial requires that you have been on a stable dose of Ursodeoxycholic Acid (UDCA) for more than 3 months or be intolerant to it. You must stop taking obeticholic acid, fibrates, colchicine, methotrexate, azathioprine, long-term systemic corticosteroids, and certain other medications before joining the trial. It's best to discuss your current medications with the study team to see if any need to be stopped.

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

Research shows that Seladelpar, a drug that helps regulate bile acid levels, 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}

Is Seladelpar safe for humans?

Seladelpar has been studied in several clinical trials for primary biliary cholangitis, and these studies have evaluated its safety over periods ranging from 3 months to 2 years. The trials generally found it to be safe, with no major safety concerns reported. ^{1 2 3 4 5}

What makes the drug Seladelpar unique for treating 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 standard treatment with ursodeoxycholic acid. ^{1 2 3 4 6}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for adults aged 18-75 with Primary Biliary Cholangitis (PBC) who haven't fully responded to or can't tolerate Ursodeoxycholic Acid. Participants must have certain levels of alkaline phosphatase, use dual contraception methods if they're of reproductive potential, and not have a history of drug abuse or recent treatments that could interfere with the study.

Inclusion Criteria

I have been on UDCA for the last year or am intolerant to it, with my last dose over 3 months ago.

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

ALP >1×ULN and <1.67×ULN

Exclusion Criteria

Laboratory parameters measured by the Central Laboratory at screening

Clinically important alcohol consumption, defined as more than 2 drink units per day in women and 3 drink units per day in men, or inability to quantify alcohol intake reliably

I haven't taken immunosuppressant drugs in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Seladelpar 10 mg or placebo for 52 weeks to assess the normalization of alkaline phosphatase levels

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Seladelpar

Trial Overview The IDEAL trial is testing whether Seladelpar can normalize alkaline phosphatase levels in PBC patients compared to a placebo. It's designed for those who don’t respond well to standard treatment. The participants will be randomly assigned either Seladelpar 10 mg or a placebo.

Participant Groups

Group I: Seladelpar Experimental Treatment 1 Intervention

Participants will receive Seladelpar 10 mg one capsule daily for up to 52 weeks.

Group II: Placebo Experimental Treatment 1 Intervention

Participants will receive placebo-to-match one capsule daily for up to 52 weeks.

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]