Seladelpar for Primary Biliary Cholangitis

(AFFIRM Trial)

Recruiting at 175 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effects of a new treatment, Seladelpar, for individuals with primary biliary cholangitis (PBC), a liver disease. Researchers aim to assess Seladelpar's effectiveness in those with PBC and compensated cirrhosis (early-stage liver scarring). The trial will compare Seladelpar to a placebo (a substance with no active treatment) to evaluate its effectiveness. Individuals diagnosed with PBC and showing signs of cirrhosis are suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that Seladelpar is likely to be safe for humans?

Research has shown that seladelpar is safe for treating primary biliary cholangitis (PBC). One study found that it improved liver function and reduced itching in PBC patients without causing serious side effects. The most common side effects were headaches and stomach issues, typical for many treatments. Seladelpar has also received fast-track approval from the FDA for treating PBC, indicating it meets certain safety standards. This approval suggests that the treatment is supported by solid safety data. ^{1 2 3 4 5}

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

Unlike the standard treatments for Primary Biliary Cholangitis, such as ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), Seladelpar works by targeting a different biological pathway. Specifically, it activates the peroxisome proliferator-activated receptor delta (PPAR-delta), which plays a role in reducing inflammation and improving liver function. Researchers are excited about Seladelpar because it offers a new mechanism of action that could provide relief for patients who do not respond adequately to existing therapies. This innovative approach may lead to better liver health with potentially fewer side effects.

What evidence suggests that Seladelpar might be an effective treatment for Primary Biliary Cholangitis?

Research has shown that seladelpar, which participants in this trial may receive, effectively treats primary biliary cholangitis (PBC). In a key study, 62% of patients experienced improved liver function. Seladelpar also reduced severe itching, a common PBC symptom. The treatment improved liver health by addressing bile flow issues. The FDA granted seladelpar accelerated approval due to its significant benefits for PBC patients, based on strong evidence from well-controlled studies. ^{1 3 4 5 6}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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]

Citations

1. gilead.com gilead.com/news/news-details/2024/gileads-livdelzi-seladelpar-granted-accelerated-approval-for-primary-biliary-cholangitis-by-us-fda

Gileads Livdelzi Seladelpar Granted Accelerated Approval ... Gilead's Livdelzi (Seladelpar) Granted Accelerated Approval for Primary Biliary Cholangitis by US FDA – First and Only Treatment to Demonstrate Statistically ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12394184/

The Efficacy and Safety of Seladelpar for Primary Biliary ... Seladelpar improved liver biomarkers of cholestasis and reduced pruritus in patients with PBC without significantly increasing the adverse ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/217899Orig1s000IntegratedR.pdf

217899Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov Substantial evidence of effectiveness for seladelpar in patients with PBC was established using data from one adequate and well-controlled ...

4. livdelzihcp.com livdelzihcp.com/efficacy-pruritus

Efficacy Data | LIVDELZI® (seladelpar) 62% of patients achieved biochemical response with LIVDELZI 1. RESPONSE was a 12-month, randomized, double-blind phase 3 pivotal trial that assessed the ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03301506

Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) An open label long-term study to evaluate the safety and tolerability of seladelpar in subjects with primary biliary cholangitis (PBC).

6. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/lyvdelzi

Lyvdelzi (previously Seladelpar Gilead) - EMA - European Union It must submit results from a study evaluating the long-term effectiveness and safety of Lyvdelzi in patients with primary biliary cholangitis. Every year ...