Elafibranor for Primary Biliary Cholangitis

(ELSPIRE Trial)

Recruiting at 76 trial locations

Overseen By Ipsen Clinical Study Enquiries

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Ipsen

Must be taking: Ursodeoxycholic acid

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

Disqualifiers: Other liver diseases, Cirrhosis, HIV, others

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

The participants in this study will have confirmed PBC with inadequate response or intolerance to Ursodeoxycholic acid (UDCA), which is a medication used in the management and treatment of cholestatic liver disease. Primary biliary cholangitis is a slowly progressive disease characterised by damage of the bile ducts in the liver, leading to a build-up of bile acids which causes further damage. The liver damage in PBC may lead to scarring (cirrhosis). PBC may also be associated with multiple symptoms. Many patients with PBC may require a liver transplant or may die if the disease progresses and a liver transplant is not done. This study will compare a daily dose of elafibranor (the study drug) to a daily dose of placebo (a dummy treatment). The main aim of this study is to determine if elafibranor is better than placebo in reducing ALP levels to a normal value. High ALP levels in the blood can indicate liver disease. There will be three periods in this study: A screening period (up to 8 weeks) to assess whether the participant can take part; a treatment period (up to 52 weeks) where eligible participants will be grouped as per their blood ALP levels and randomly assigned to either receive elafibranor or placebo, and a follow-up period (4 weeks) where participants' health will be monitored. Participants will be twice as likely to receive elafibranor than placebo (2:1 ratio). Participants will undergo blood sampling, urine collections, physical examinations, clinical evaluations, electrocardiograms (ECG: recording of the electrical activity of heart), ultrasound examinations (a noninvasive test that passes a probe over skin to look at the bladder, urinary tract, and liver), and Fibroscan® examinations (a noninvasive test that passes a probe on skin to measure stiffness of the liver). They will also be asked to fill in questionnaires. Each participant will be in this study for up to 64 weeks (15 months).

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking certain medications, such as fibrates, seladelpar, glitazones, and others, at least 3 months before the screening visit. If you are taking UDCA or medications for pruritus, you must be on a stable dose for at least 3 months before joining the trial.

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 to help patients with primary biliary cholangitis who do not fully respond to standard treatment. While its effectiveness is still being evaluated, similar drugs that target the same proteins have shown promise in improving liver function in these patients. ^{1 2 3 4 5}

Is Elafibranor safe for humans?

Elafibranor has been studied for safety in patients with primary biliary cholangitis, and it is generally considered safe for human use, although specific side effects or risks were not detailed in the available research. ^{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 PPARα/δ agonist, which means it activates specific proteins involved in fat metabolism and inflammation, potentially offering benefits for patients who do not fully respond to the standard treatment, ursodeoxycholic acid. ^{1 2 3 4 8}

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 Ursodeoxycholic Acid. They must have had high ALP levels for at least 6 months, positive antibodies indicating PBC, and a liver biopsy consistent with PBC. Men in the trial must use contraception during and for 30 days after the study.

Inclusion Criteria

I have been on a stable dose of UDCA for at least 3 months or stopped it due to intolerance over 3 months ago.

ALP >1 × ULN and <1.67 × ULN

I have been diagnosed with PBC based on elevated ALP, positive AMA or specific liver biopsy results.

Exclusion Criteria

Known hypersensitivity to the investigational product or to any of the excipients of elafibranor

I am mentally capable of understanding and following the study's requirements.

I do not have conditions like Paget's disease that affect my ALP levels.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 8 weeks

Treatment

Participants receive either elafibranor or placebo daily for up to 52 weeks

up to 52 weeks

Regular visits for blood sampling, urine collections, physical examinations, ECG, ultrasound, and Fibroscan® examinations

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Elafibranor (PPAR agonist)

Trial Overview The trial is testing Elafibranor against a placebo in patients with PBC. It aims to see if Elafibranor lowers ALP levels better than a dummy treatment. Participants will be chosen randomly to receive either Elafibranor or placebo in a 2:1 ratio and monitored through blood tests, physical exams, ECGs, ultrasounds, Fibroscans®, and questionnaires.

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 before breakfast with a glass of water at approximately the same time 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

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]

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]