Elafibranor for Primary Sclerosing Cholangitis

(ELMWOOD Trial)

Recruiting at 64 trial locations

Overseen By Ipsen Clinical Study Enquiries

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ipsen

Must be taking: Ursodeoxycholic acid

Disqualifiers: Chronic liver disease, Hepatitis B, Hepatitis C, HIV, others

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

68 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing elafibranor, a medication, in people with Primary Sclerosing Cholangitis (PSC), a rare liver disease. PSC causes bile ducts to get damaged, leading to more liver problems. The study will evaluate if elafibranor is safe and effective in reducing liver inflammation and improving bile flow.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that certain medications, like those for inflammatory bowel disease and pruritus, be on a stable dose for at least 3 months before the trial. If you're taking ursodeoxycholic acid, you must have been on a stable dose for 6 months or have stopped it 3 months before the trial.

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

Research on Elafibranor has shown it to be a promising treatment for primary biliary cholangitis, a similar liver condition, by targeting specific receptors in the body. Although direct evidence for primary sclerosing cholangitis is limited, the drug's mechanism may offer potential benefits for this condition as well. ^{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 in humans based on these studies. ^{1 2 4 6 7}

How is the drug Elafibranor unique in treating primary sclerosing cholangitis?

Elafibranor is unique because it is an oral drug that acts as a dual agonist (activator) of PPARα and PPARδ, which are proteins involved in regulating metabolism and inflammation. This mechanism is different from other treatments like ursodeoxycholic acid, which not all patients respond to, highlighting the need for new therapies. ^{1 2 3 4 8}

Research Team

Ipsen Medical, Director

Principal Investigator

Ipsen

Eligibility Criteria

Adults with Primary Sclerosing Cholangitis (PSC) can join this trial. They must have stable Inflammatory Bowel Disease if present, no recent severe liver issues or cancer, and be on a steady dose of certain medications like ursodeoxycholic acid. Participants need to use approved contraception methods and not be pregnant or breastfeeding.

Inclusion Criteria

I have been diagnosed with PSC and have had high ALP levels for over 6 months.

Exclusion Criteria

I have previously taken elafibranor.

I have a history of chronic liver disease or specific liver conditions.

I have had serious liver problems as outlined in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-Blind Treatment

Participants receive either elafibranor or placebo for 12 weeks to evaluate safety and efficacy

12 weeks

Regular visits for monitoring and assessments

Open-Label Extension

Participants receive elafibranor 120 mg for long-term safety and efficacy evaluation

96 weeks

Periodic visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Elafibranor
• Placebo

Trial Overview The trial is testing Elafibranor at two different doses (80 mg and 120 mg) against placebos matched for each dose. The goal is to see how safe Elafibranor is and how well it works in treating PSC by comparing its effects on liver function tests and other disease-related measures.

Participant Groups

Group I: Open-Label Extension Period: Elafibranor 120 mg Experimental Treatment 1 Intervention

Participant will receive one tablet per day (elafibranor 120 mg) over the 96 weeks in Open-Label extension period.

Group II: Double-Blind Period: Elafibranor 80 mg Experimental Treatment 2 Interventions

Participant will receive two tablets per day (one tablet of elafibranor 80 mg + 1 tablet of placebo matching the 120 mg sized tablet) over the 12 weeks in Double-blind period.

Group III: Double-Blind Period: Elafibranor 120 mg Experimental Treatment 2 Interventions

Participant will receive 2 tablets per day (one tablet of elafibranor 120 mg + 1 tablet of placebo matching the 80 mg sized tablet) over the 12 weeks in Double-blind period.

Group IV: Double-Blind Period: Placebo Placebo Group 1 Intervention

Participant will receive 2 placebo tablets per day (one matching the 80 mg sized tablet + one matching the 120 mg sized tablet) over the 12 weeks in Double-blind period.

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 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 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]

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

Emerging drugs for the treatment of primary sclerosing cholangitis. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Pembrolizumab Induced Sclerosing Cholangitis: Why You Need a Liver Biopsy. [2023]

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

Seladelpar improved measures of pruritus, sleep, and fatigue and decreased serum bile acids in patients with primary biliary cholangitis. [2022]