Seladelpar for Primary Biliary Cholangitis

(AFFIRM Trial)

Recruiting at 87 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: CymaBay Therapeutics, Inc.

Disqualifiers: Decompensated cirrhosis, Portal vein thrombosis, others

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: 36 months

318 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing Seladelpar, a medication that may help people with a specific liver disease called Primary Biliary Cholangitis (PBC) and early-stage cirrhosis. The drug aims to reduce liver inflammation and damage, potentially improving liver health. Seladelpar has shown promising results in previous studies for PBC, despite initial safety concerns.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

What data supports the effectiveness of the drug Seladelpar for treating 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 for safety in people with primary biliary cholangitis, showing it is generally safe over periods ranging from 3 months to 2 years, with no major safety concerns reported in these studies. ^{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 4 5 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) and compensated cirrhosis. Participants must have a Child-Pugh (CP) Score of A or B, use dual contraception methods, and be able to follow the study's procedures. Exclusions include those with conditions that may interfere with the study, prior liver transplants, decompensated cirrhosis, certain lab values outside set limits, or previous seladelpar exposure.

Inclusion Criteria

I have been diagnosed with cirrhosis.

I have been previously diagnosed with primary biliary cholangitis (PBC).

You have a CP Score that falls within the range of A or B.

Exclusion Criteria

Platelet count ≤75×10^3/µL

Serum alpha-fetoprotein (AFP) >20 ng/mL

I have had a liver transplant or am waiting for one.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Seladelpar or placebo to evaluate clinical outcomes in PBC and compensated cirrhosis

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Seladelpar

Trial Overview The trial is testing Seladelpar at a dose of 10 mg against a placebo to see its effect on clinical outcomes in patients with PBC and compensated cirrhosis. The goal is to determine if Seladelpar can improve health markers in these patients compared to not receiving the active drug.

Participant Groups

Group I: Seladelpar Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 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?

CymaBay Therapeutics, Inc.

Lead Sponsor

Trials

23

Recruited

3,200+

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

Findings from Research

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 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]

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 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]

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. 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]

2. Netherlands pubmed.ncbi.nlm.nih.gov

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

3. 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]

4. 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]

5. 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]

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

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