Elafibranor for Primary Biliary Cholangitis

(ELSPIRE Trial)

Not currently recruiting at 89 trial locations

Overseen By Ipsen Clinical Study Enquiries

Age: 18+

Sex: Any

Trial Phase: Phase 3

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) 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: Unknown

Duration: up to 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether elafibranor can aid individuals with primary biliary cholangitis (PBC), a liver disease that damages bile ducts and causes harmful bile build-up. The study aims to determine if elafibranor can reduce high levels of the liver enzyme ALP, an indicator of liver disease. Participants will receive either elafibranor or a placebo for up to 52 weeks. The trial seeks individuals diagnosed with PBC who have not responded well to the common treatment UDCA or cannot tolerate it. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially bringing a new treatment to market.

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.

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

Research has shown that elafibranor was well-tolerated in past studies for primary biliary cholangitis (PBC). Patients who took elafibranor experienced improvements in symptoms such as tiredness and sleep issues. Importantly, these studies found that elafibranor led to better liver function test results compared to a placebo, with no major safety concerns reported.

Although detailed information on long-term effects is limited, the treatment has shown promise for up to three years. This suggests that elafibranor is generally safe for humans, with manageable side effects. However, healthcare professionals must monitor participants to ensure safety throughout the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Elafibranor is unique because it targets the root cause of primary biliary cholangitis (PBC) by activating PPAR alpha and delta receptors, which are involved in regulating inflammation and bile acid metabolism. Unlike current treatments like ursodeoxycholic acid or obeticholic acid, which primarily focus on improving bile flow, elafibranor offers a new mechanism of action that may address inflammation directly. Researchers are excited about this treatment because it has the potential to provide more comprehensive management of PBC symptoms and could potentially improve liver health more effectively than existing options.

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 help treat primary biliary cholangitis (PBC). Studies have found that elafibranor lowers alkaline phosphatase (ALP) levels, often elevated in people with PBC and indicative of liver issues. Patients taking elafibranor reported feeling less tired and experiencing better sleep. Although researchers are still studying the long-term effects, these results suggest that elafibranor could be a promising option for those with PBC who do not respond well to other treatments. ^{1 3 5 6 7}

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 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.

Evidence of any other unstable or untreated clinically significant conditions that are not well controlled

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Elafibranor

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.

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 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 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]

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]

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 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 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 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]

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. 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.

3. 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.

4. 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 ...

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

IQIRVO Efficacy | IQIRVO Trial Results | Official HCP Site The only pivotal study for PBC in which. 40% of patients had baseline ALP >3 x ULN2. The ELATIVE® trial was a double-blind, randomized, placebo-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. 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.