Elafibranor for Primary Biliary Cholangitis

(ELFIDENCE Trial)

Recruiting at 128 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

Trial Summary

What is the purpose of this trial?

This trial is testing elafibranor, a medication for people with Primary Biliary Cholangitis (PBC) who do not respond to or cannot take the usual treatment. PBC is a liver disease that can lead to severe damage if untreated. Elafibranor aims to reduce harmful substances in the liver to prevent further damage. The study will also check if the medication is safe and helps with symptoms like itching and tiredness. Elafibranor is being tested as a new treatment option for PBC patients who do not respond to or cannot tolerate the standard treatments.

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.

What data supports the effectiveness of the drug Elafibranor for treating primary biliary cholangitis?

Research suggests that Elafibranor, which works by activating certain proteins in the body, is being studied for its potential benefits in treating primary biliary cholangitis, especially for patients who do not fully respond to existing treatments like ursodeoxycholic acid. ^{1 2 3 4 5}

Is Elafibranor safe for humans?

Elafibranor has been studied for safety in patients with primary biliary cholangitis, a liver disease, and is generally considered safe for human use in clinical trials. ^{1 2 4 6 7}

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 agonist (activator) of PPARα and PPARδ, which are proteins involved in regulating liver function and immunity. This mechanism is different from existing treatments like ursodeoxycholic acid and obeticholic acid, and it may offer benefits for patients who do not fully respond to these standard therapies. ^{1 2 4 8 9}

Research Team

Ipsen Medical Director

Principal Investigator

Ipsen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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 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]

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]

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]

References

1. 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]

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

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

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

Continuing Medical Education Questions: November 2021. [2023]

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

Work in Progress: Drugs in Development. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incomplete UDCA response may improve outcomes. [2022]

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

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

7. 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]

8. Italy pubmed.ncbi.nlm.nih.gov

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

Peroxisome Proliferator-Activated Receptors Regulate Hepatic Immunity and Assist in the Treatment of Primary Biliary Cholangitis. [2022]