Elafibranor for Primary Biliary Cholangitis

(ELATIVE Trial)

Not currently recruiting at 128 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug elafibranor can help people with Primary Biliary Cholangitis (PBC), a liver disease that damages bile ducts and leads to liver scarring. The study targets those who haven't responded well to or can't tolerate the common treatment, ursodeoxycholic acid. Participants will receive either elafibranor or a placebo to determine if it can lower a specific blood marker linked to the disease and improve symptoms like itchy skin and tiredness. Individuals diagnosed with PBC who can't manage their symptoms with current treatments might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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

Research has shown that elafibranor is generally well-tolerated. Studies indicate it can significantly improve liver function tests in patients with primary biliary cholangitis (PBC), a liver disease that harms bile ducts. In these studies, patients taking elafibranor reported feeling less tired and sleeping better.

Regarding safety, trials have found no major concerns. Patients have used elafibranor for up to three years without significant side effects, suggesting it is relatively safe for long-term use. However, like any treatment, some side effects might occur. Always consult a doctor about potential risks before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Elafibranor for treating Primary Biliary Cholangitis (PBC) because it offers a new approach by targeting a different pathway than current treatments. While current therapies like ursodeoxycholic acid and obeticholic acid focus on bile flow or FXR activation, Elafibranor activates PPAR alpha and delta receptors, which help reduce liver inflammation and fibrosis. This unique mechanism could offer an alternative for patients who don't respond well to existing treatments, potentially improving liver function and patient outcomes.

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

Research has shown that elafibranor, which participants in this trial may receive, can greatly improve liver health in people with Primary Biliary Cholangitis (PBC). Studies have found that elafibranor lowers alkaline phosphatase levels more effectively than a placebo, an important indicator of liver damage. In long-term studies, more than half of the patients responded positively, with some even reaching normal alkaline phosphatase levels. Elafibranor also appears more effective than seladelpar in improving these liver markers. These findings suggest that elafibranor could be a promising option for those who haven't had success with other treatments. ^{1 2 4 5 6}

Who Is on the Research Team?

Ipsen Medical Director

Principal Investigator

Ipsen

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2306185

Efficacy and Safety of Elafibranor in Primary Biliary ... Treatment with elafibranor resulted in significantly greater improvements in relevant biochemical indicators of cholestasis than placebo.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37962077/

Efficacy and Safety of Elafibranor in Primary Biliary ... Treatment with elafibranor resulted in significantly greater improvements in relevant biochemical indicators of cholestasis than placebo.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04526665

Study of Elafibranor in Patients With Primary Biliary ... The main aim of this study is to determine if elafibranor (the study drug) is better than placebo (a dummy treatment) at decreasing the levels of a specific ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11669080/

Second‐Line Treatment for Patients With Primary Biliary ... Among second line therapies for patients with PBC, elafibranor is slightly more effective in obtaining biochemical response than seladelpar.

5. gut.bmj.com gut.bmj.com/content/74/Suppl_1/A206.2

P199 Long-term efficacy and safety of elafibranor in ... In patients receiving continuous elafibranor, 34/61 (56%) at Week 104 and 11/13 (85%) at Week 156 had biochemical response, ALP normalization occurred in 8/61 ( ...

6. ipsen.com ipsen.com/press-releases/iqirvo-elafibranor-data-shows-efficacy-and-safety-for-up-to-3-years-in-patients-with-pbc-with-improvements-in-fatigue-and-pruritus-2982128/

Iqirvo® (elafibranor) data shows efficacy and safety for up ... Patients treated with Iqirvo reported improvement in fatigue and sleep, across several patient-reported outcome measures.