Elafibranor for Primary Biliary Cholangitis

(ELFIDENCE Trial)

Recruiting at 184 trial locations

Overseen By Ipsen Clinical Study Enquiries

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ipsen

Must not be taking: Fibrates, Glitazones, Corticosteroids, others

Disqualifiers: Hepatitis, HIV, Alcohol abuse, 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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 3.5 years

276 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called elafibranor for individuals with Primary Biliary Cholangitis (PBC), a condition that damages the liver's bile ducts and often leads to cirrhosis (scarring of the liver). The trial aims to determine if elafibranor can prevent disease progression compared to a placebo (a dummy treatment). It also examines how the treatment affects symptoms like itching and tiredness over the long term. Individuals with confirmed PBC and cirrhosis who haven't experienced certain liver-related complications might be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as fibrates, seladelpar, glitazones, and others, at least 3 months before the study. It's best to discuss your current medications with the study team to see if any need to be stopped.

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

Research has shown that elafibranor may help treat Primary Biliary Cholangitis (PBC). In various studies, patients taking elafibranor experienced reduced fatigue and improved sleep, both crucial for daily life. Elafibranor also enhanced certain liver health indicators.

Regarding safety, studies suggest that elafibranor is generally safe, with most participants not experiencing serious side effects. However, more long-term research is needed to fully understand all possible effects. This information may assist in weighing the benefits and risks if considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Elafibranor is unique because it targets a different pathway in treating Primary Biliary Cholangitis (PBC). While most treatments for PBC, like ursodeoxycholic acid (UDCA) and obeticholic acid, focus on improving bile flow and reducing liver damage, Elafibranor acts as a dual agonist of the peroxisome proliferator-activated receptors (PPAR) alpha and delta. This mechanism may help reduce inflammation and improve liver function by addressing both metabolic and inflammatory pathways. Researchers are excited about Elafibranor because it offers a novel approach that could enhance liver health and provide relief for patients who don't fully respond to current treatments.

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

Research has shown that elafibranor can help treat primary biliary cholangitis (PBC). In a previous study, patients taking elafibranor showed better results in liver-related blood tests, specifically in alkaline phosphatase levels, where lower levels indicate less liver damage. Elafibranor also benefits patients who did not improve with UDCA, a common PBC treatment. Although more long-term data is needed, strong evidence suggests it can improve liver function in PBC patients. Participants in this trial will receive either 80 mg of elafibranor or a placebo to further evaluate its effectiveness. ^{1 5 6 7 8}

Who Is on the Research Team?

Ipsen Medical Director

Principal Investigator

Ipsen

Are You a Good Fit for This Trial?

Adults over 18 with Primary Biliary Cholangitis (PBC) who haven't responded well to or can't tolerate the standard treatment, UDCA. They should be stable on any itch-management meds for at least 3 months and not have other significant health issues that could affect their participation. People with a history of certain liver diseases, substance abuse, cancer within the last five years, or specific medical conditions are excluded.

Inclusion Criteria

Participants must adhere to the governing laws regarding contraceptive methods while engaging in clinical research.

I have been on a stable dose of UDCA for 12 months or can't tolerate UDCA.

I've been on the same itch medication dose for at least 3 months.

Exclusion Criteria

Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m2 per the Modification of Diet in Renal Disease (MDRD)-6 Study formula at SV1.

International normalised ratio (INR) >1.5 in the absence of anticoagulant therapy.

I do not have other liver diseases like hepatitis or fatty liver disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a daily dose of elafibranor or placebo for up to 3.5 years

3.5 years

Assessed every 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Elafibranor

Trial Overview The trial is testing Elafibranor against a placebo in patients with PBC who don’t respond to UDCA. It aims to see if Elafibranor can prevent disease worsening better than a dummy pill over up to seven years while also monitoring long-term safety and effects on symptoms like itching and fatigue.

How Is the Trial Designed?

Group I: Elafibranor 80 mg Experimental Treatment 1 Intervention

Participants will take 1 tablet of elafibranor 80 mg per day orally before breakfast with a glass of water at approximately the same time each morning.

Group II: Placebo Placebo Group 1 Intervention

Participants will take 1 placebo tablet per day orally (matching the 80 mg elafibranor sized tablet) before breakfast with a glass of water at approximately the same time each morning.

Elafibranor is already approved in United States for the following indications:

Approved in United States as Iqirvo for:

• Primary biliary cholangitis (PBC) in adults with intolerance of inadequate response to ursodeoxycholic acid

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

Published Research Related to This Trial

In a study of 120 patients with primary biliary cholangitis (PBC), fenofibrate therapy significantly improved biochemical response rates compared to those receiving only ursodeoxycholic acid (UDCA), with 41% of fenofibrate patients meeting the Toronto criteria for response versus only 7% in the UDCA group.

Fenofibrate was associated with better transplant-free and decompensation-free survival, but caution is advised in cirrhotic patients due to potential rapid increases in bilirubin and a 22% discontinuation rate due to adverse effects like abdominal pain and myalgias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incomplete UDCA response may improve outcomes. Cheung, AC., Lapointe-Shaw, L., Kowgier, M., 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 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 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 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]

The multicentric observational study compared the effects of obeticholic acid and fibrates in patients with primary biliary cholangitis, highlighting their efficacy in managing this liver disease.

Results indicated that obeticholic acid may provide superior benefits in improving liver function tests compared to fibrates, suggesting it could be a more effective treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuing Medical Education Questions: November 2021. Richter, SJ.[2023]

Fibrates, such as bezafibrate and fenofibrate, have been shown to effectively reduce alkaline phosphatase levels and improve clinical outcomes in patients with primary biliary cholangitis who do not respond adequately to ursodeoxycholic acid (UDCA) monotherapy.

Unlike obeticholic acid, which can worsen itching, fibrates have been found to relieve pruritus, making them a more favorable option for managing symptoms in this autoimmune liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peroxisome Proliferator-Activated Receptors Regulate Hepatic Immunity and Assist in the Treatment of Primary Biliary Cholangitis. Wang, C., Shi, Y., Wang, X., 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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12055048/

Iqirvo for primary biliary cholangitis – efficacy, safety, and ... The phase 3 ELATIVE trial demonstrated significant improvements in alkaline phosphatase levels, but data on long-term outcomes are limited.

2. 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 ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/23995270.2025.2580910

Elafibranor in the treatment of primary biliary cholangitis Recent clinical trials have demonstrated that elafibranor can improve liver-related blood tests in PBC patients who did not respond to UDCA.

4. iqirvohcp.com iqirvohcp.com/iqirvo-results/trial-results

IQIRVO Efficacy | IQIRVO Trial Results | Official HCP Site Review the ELATIVE Phase 3 Trial results including primary and secondary endpoints for IQIRVO ... Efficacy and safety of elafibranor in primary biliary cholangitis.

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/218860Orig1s000IntegratedR.pdf

218860Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov Substantial evidence of effectiveness for elafibranor in patients with PBC was established using data from one adequate and well-controlled ...

6. iqirvohcp.com iqirvohcp.com/safety-tolerability

IQIRVO PBC | Safety & Tolerability | Official HCP Site Review safety and tolerability results of IQIRVO in the ELATIVE study. See Important Safety and Prescribing Information.

7. ipsen.com ipsen.com/us/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.

8. 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.