Elafibranor for Primary Sclerosing Cholangitis

(ELMWOOD Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called elafibranor to determine its effectiveness for people with Primary Sclerosing Cholangitis (PSC), a rare liver disease that damages the bile ducts. Participants will receive either the drug or a placebo to compare their effects. The study will primarily focus on the safety of elafibranor and its impact on blood tests and disease activity. Individuals with PSC who have had elevated liver tests for more than six months might be suitable candidates for this trial. As a Phase 2 trial, this research aims to measure the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important early findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found elafibranor to be safe for people with Primary Sclerosing Cholangitis (PSC). Over 12 weeks, it maintained a good safety record, with most patients experiencing no serious side effects. Additionally, some participants showed improved blood test results compared to those on a placebo. These findings suggest that elafibranor might be a safe short-term treatment option for PSC. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PSC?

Elafibranor is unique because it targets the farnesoid X receptor (FXR), which plays a key role in bile acid regulation and liver health. This mechanism is different from the standard of care for Primary Sclerosing Cholangitis, which often involves managing symptoms with medications like ursodeoxycholic acid or addressing complications with endoscopic or surgical interventions. Researchers are excited about elafibranor because its targeted approach could potentially address the underlying disease process rather than just alleviating symptoms. Additionally, its oral administration offers a convenient option for patients, potentially improving adherence and outcomes.

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

In this trial, participants will receive varying doses of elafibranor or a placebo to assess its effectiveness for Primary Sclerosing Cholangitis (PSC). Previous studies have shown that elafibranor holds promise for individuals with PSC. It was well tolerated, causing few side effects. Over 12 weeks, patients taking elafibranor demonstrated better biochemical improvements than those on a placebo. Specifically, blood tests revealed positive changes, indicating the treatment's effectiveness. The improvements were dose-dependent, with different drug amounts producing varying effects on the condition. These findings suggest that elafibranor could effectively manage PSC. ^{1 2 4 6 7}

Who Is on the Research Team?

Ipsen Medical, Director

Principal Investigator

Ipsen

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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 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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40350321/

Safety and efficacy of elafibranor in primary sclerosing ... Elafibranor was well tolerated in people with PSC and associated with greater biochemical improvements over 12 weeks compared with placebo.

2. ipsen.com ipsen.com/press-releases/late-breaking-elafibranor-primary-sclerosing-cholangitis-psc-data-demonstrates-favorable-safety-profile-and-significant-efficacy-in-second-potential-rare-liver-disease-indication-3067100/

Late-breaking elafibranor primary sclerosing cholangitis ... Elafibranor showed a favorable safety profile and demonstrated dose-dependent efficacy over 12 weeks for people living with PSC, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05627362

NCT05627362 | A Study to Assess Safety and ... This study will evaluate the effects of elafibranor (the study drug) in participants with Primary Sclerosing Cholangitis (PSC).

4. sciencedirect.com sciencedirect.com/science/article/pii/S0168827825002521

Safety and efficacy of elafibranor in primary sclerosing ... Elafibranor was well tolerated in people with PSC and associated with greater biochemical improvements over 12 weeks compared with placebo.

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. journal-of-hepatology.eu journal-of-hepatology.eu/article/S0168-8278%2825%2900252-1/fulltext

Safety and efficacy of elafibranor in primary sclerosing ... In this double-blind, randomized, placebo-controlled phase II trial in adults with large-duct PSC, elafibranor was well tolerated and ...