Elafibranor for Primary Biliary Cholangitis

(ELATIVE Trial)

Recruiting at 114 trial locations

Overseen By Genfit

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ipsen

Must be taking: Ursodeoxycholic acid

Must not be taking: Fibrates, Glitazones, Obeticholic acid, others

Disqualifiers: Other liver disease, HIV, Cancer, 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

Compensation: Varies

Number of Visits: Unknown

161 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a drug called elafibranor on patients with Primary Biliary Cholangitis (PBC) who haven't responded to standard treatment. The goal is to see if elafibranor can lower a specific liver enzyme and improve symptoms. Initially, participants will receive different treatments, and later, all will receive elafibranor for an extended period. Elafibranor has shown promise in improving symptoms in previous trials.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. Specifically, you must not use fibrates, glitazones, obeticholic acid, and several other specified drugs for a certain period before screening. The protocol does not mention stopping all current medications, so it's best to discuss your specific medications with the trial team.

Is Elafibranor safe for humans?

Research on Elafibranor, a drug being studied for primary biliary cholangitis, has focused on its safety and effectiveness. While specific safety data is not detailed in the provided abstracts, the studies imply ongoing evaluation of its safety profile in humans. ^{1 2 3 4 5}

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

Elafibranor is unique because it is an oral drug that works as a dual PPARα/δ agonist, which means it activates two specific proteins involved in regulating liver function and inflammation. This mechanism is different from other treatments like ursodeoxycholic acid and obeticholic acid, which not all patients respond to, highlighting the need for new therapies. ^{3 4 5 6 7}

Research Team

Ipsen Medical Director

Principal Investigator

Ipsen

Eligibility Criteria

This trial is for adults aged 18-75 with Primary Biliary Cholangitis (PBC) who haven't responded well to or can't tolerate Ursodeoxycholic Acid. They must have a certain level of ALP enzyme and be using effective contraception if applicable. Exclusions include HIV, pregnancy, alcohol abuse, previous Elafibranor use, certain liver conditions, high levels of liver enzymes or bilirubin, low albumin or abnormal blood clotting.

Inclusion Criteria

I have been diagnosed with primary biliary cholangitis.

I have been on UDCA for 12 months or can't tolerate it.

I am either unable to have children or will use effective birth control during and for 1 month after the study.

Exclusion Criteria

I do not have any health conditions, including other cancers, that could shorten my life to under 2 years.

Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 5x ULN

Serum creatinine > 1.5 mg/dL

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive a daily dose of elafibranor or placebo for a minimum of one year and a maximum of two years

52-104 weeks

Regular visits for monitoring and assessment

Treatment Part 2 (Open-label Extension)

All participants receive elafibranor for up to 5 years or until the total treatment duration reaches 6 years

Up to 260 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Elafibranor 80mg
• Placebo

Trial Overview The study tests the effects of daily oral Elafibranor (80mg) versus placebo on bile flow impairment in PBC patients intolerant or unresponsive to standard treatment. Participants are randomly assigned in a 2:1 ratio to receive either Elafibranor or placebo.

Participant Groups

Group I: Elafibranor 80mg open label Experimental Treatment 1 Intervention

Study participants will take 1 tablet per day orally before breakfast with a glass of water each morning

Group II: Elafibranor 80mg double-blind Experimental Treatment 1 Intervention

Study participants will take 1 tablet per day orally before breakfast with a glass of water each morning

Group III: Placebo Placebo Group 1 Intervention

Study participants will take 1 tablet per day orally before breakfast with a glass of water each morning

Who Is Running the Clinical Trial?

Ipsen

Lead Sponsor

Trials

358

Recruited

74,600+

David Loew

Ipsen

Chief Executive Officer since 2020

BA in Business Administration and MBA from the University of St. Gallen, Switzerland

Sandra Silvestri

Ipsen

Chief Medical Officer since 2023

MD, PhD

Genfit

Lead Sponsor

Trials

20

Recruited

3,500+

Findings from Research

In the Phase 2b GLIMMER study involving 147 adults with primary biliary cholangitis and moderate-to-severe itching, linerixibat showed a dose-dependent reduction in itch scores, particularly at higher doses, although the primary analysis did not show significant differences from placebo.

Diarrhea was the most common side effect associated with linerixibat, and its incidence increased with the dose, indicating a need for careful dose management in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLIMMER: A Randomized Phase 2b Dose-Ranging Trial of Linerixibat in Primary Biliary Cholangitis Patients With Pruritus. Levy, C., Kendrick, S., Bowlus, CL., et al.[2023]

Obeticholic acid and off-label fibrate derivatives are effective next-generation therapies for patients with primary biliary cholangitis who do not respond well to the standard treatment, ursodeoxycholic acid.

Research is focusing on modulating nuclear receptor pathways to improve biliary excretion and reduce inflammation and fibrosis, which could lead to better management of the disease and its symptoms, such as pruritus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary biliary cholangitis: pathogenesis and therapeutic opportunities. Gulamhusein, AF., Hirschfield, GM.[2020]

In a 12-week phase II trial involving 45 adults with primary biliary cholangitis (PBC) who did not respond adequately to ursodeoxycholic acid, elafibranor significantly reduced alkaline phosphatase (ALP) levels by up to 48.3% compared to placebo, indicating its efficacy as a treatment option.

Elafibranor was found to be generally safe and well tolerated, with no exacerbation of pruritus (itching) in patients, and it also improved other disease markers, suggesting it could be a promising second-line therapy for PBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized placebo-controlled trial of elafibranor in patients with primary biliary cholangitis and incomplete response to UDCA. Schattenberg, JM., Pares, A., Kowdley, KV., et al.[2022]

In a phase 3 trial involving 161 patients with primary biliary cholangitis, elafibranor significantly improved biochemical markers of cholestasis, with 51% of patients showing a biochemical response compared to only 4% in the placebo group.

Elafibranor also led to normalization of alkaline phosphatase levels in 15% of patients, while no patients in the placebo group achieved this, although it did not significantly reduce pruritus intensity compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. Kowdley, KV., Bowlus, CL., Levy, C., et al.[2023]

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]

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 study of 106 patients with primary biliary cholangitis (PBC) who did not respond well to ursodeoxycholic acid (UDCA), adding fenofibrate (FF) to their treatment significantly reduced alkaline phosphatase (ALP) levels and improved liver transplant-free survival after one year.

Patients receiving FF alongside UDCA showed better stabilization or improvement in liver fibrosis and bile duct loss compared to those on UDCA alone, indicating that FF may enhance the overall management of PBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fenofibrate improves GLOBE and UK-PBC scores and histological features in primary biliary cholangitis. Wang, L., Sun, K., Tian, A., et al.[2023]

References

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

GLIMMER: A Randomized Phase 2b Dose-Ranging Trial of Linerixibat in Primary Biliary Cholangitis Patients With Pruritus. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Primary biliary cholangitis: pathogenesis and therapeutic opportunities. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

A randomized placebo-controlled trial of elafibranor in patients with primary biliary cholangitis and incomplete response to UDCA. [2022]

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

Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. [2023]

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

Work in Progress: Drugs in Development. [2019]

6. 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]

7. Italy pubmed.ncbi.nlm.nih.gov

Fenofibrate improves GLOBE and UK-PBC scores and histological features in primary biliary cholangitis. [2023]