Elafibranor for Primary Biliary Cholangitis (ELSPIRE Trial)
Recruiting in Palo Alto (17 mi)
+85 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Ipsen
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).
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.
24578Is 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.
23468Do 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.
12478Eligibility 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 diagnosed with PBC based on elevated ALP, positive AMA or specific liver biopsy results.
Exclusion Criteria
I am mentally capable of understanding and following the study's requirements.
My AFP levels are above 20 ng/mL, and scans indicate I might have liver cancer.
I have previously taken elafibranor.
I am not pregnant, have not tested positive for pregnancy, and am not breastfeeding.
I have a serious kidney condition.
I have or had other liver diseases.
I have had a liver transplant.
I have a history of serious liver problems.
My kidney function is reduced with an eGFR below 45.
I haven't had cancer in the last 2 years, except for certain skin cancers or cervical cancer that didn't spread.
I have had liver cancer.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Elafibranor 80 mgExperimental Treatment1 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: PlaceboPlacebo Group1 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
American Research Corporation at The Texas Liver InstituteSan Antonio, TX
University of California, DavisSacramento, CA
Peak Gastroenterology AssociatesColorado Springs, CO
University of Michigan Health SystemAnn Arbor, MI
More Trial Locations
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Who is running the clinical trial?
IpsenLead Sponsor
References
Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incomplete UDCA response may improve outcomes. [2022]Fibrates appear to improve biochemistry in patients with primary biliary cholangitis (PBC), but it is unclear which factors predict response and whether treatment improves transplant-free survival.
Work in Progress: Drugs in Development. [2019]Primary biliary cholangitis is an archetypal autoimmune disease that causes cholestasis, fibrosis, and liver failure. Ursodeoxycholic acid and obeticholic acid are approved for its treatment. Not all patients respond, some are intolerant, many have ongoing symptoms, and new therapies are required. Herein we describe drugs in development and potential future biological targets. We consider compounds acting on the farnesoid X receptor/fibroblast growth factor 19 pathway, fibrates and other agonists of the peroxisome proliferator-activated receptor family, transmembrane-G-protein-receptor-5 agonists, and several immunological agents. We also consider the roles of bile acid reuptake inhibitors, nalfurafine, and fibrates in pruritus management.
Primary biliary cholangitis: pathogenesis and therapeutic opportunities. [2020]Primary biliary cholangitis is a chronic, seropositive and female-predominant inflammatory and cholestatic liver disease, which has a variable rate of progression towards biliary cirrhosis. Substantial progress has been made in patient risk stratification with the goal of personalized care, including early adoption of next-generation therapy with licensed use of obeticholic acid or off-label fibrate derivatives for those with insufficient benefit from ursodeoxycholic acid, the current first-line drug. The disease biology spans genetic risk, epigenetic changes, dysregulated mucosal immunity and altered biliary epithelial cell function, all of which interact and arise in the context of ill-defined environmental triggers. A current focus of research on nuclear receptor pathway modulation that specifically and potently improves biliary excretion, reduces inflammation and attenuates fibrosis is redefining therapy. Patients are benefiting from pharmacological agonists of farnesoid X receptor and peroxisome proliferator-activated receptors. Immunotherapy remains a challenge, with a lack of target definition, pleiotropic immune pathways and an interplay between hepatic immune responses and cholestasis, wherein bile acid-induced inflammation and fibrosis are dominant clinically. The management of patient symptoms, particularly pruritus, is a notable goal reflected in the development of rational therapy with apical sodium-dependent bile acid transporter inhibitors.
A randomized placebo-controlled trial of elafibranor in patients with primary biliary cholangitis and incomplete response to UDCA. [2022]Patients with primary biliary cholangitis (PBC) who have an incomplete response to ursodeoxycholic acid remain at risk of disease progression. We investigated the safety and efficacy of elafibranor, a dual PPARα/δ agonist, in patients with PBC.
Fenofibrate improves GLOBE and UK-PBC scores and histological features in primary biliary cholangitis. [2023]Fenofibrate (FF) has been suggested as a second-line therapy for primary biliary cholangitis (PBC) with suboptimal response to ursodeoxycholic acid (UDCA). But its long-term effect is unclear.
GLIMMER: A Randomized Phase 2b Dose-Ranging Trial of Linerixibat in Primary Biliary Cholangitis Patients With Pruritus. [2023]GLIMMER assessed dose-response, efficacy, and safety of linerixibat, an ileal bile acid transporter inhibitor in development for cholestatic pruritus associated with primary biliary cholangitis (PBC).
Continuing Medical Education Questions: November 2021. [2023]Article Title: Obeticholic Acid and Fibrates in Primary Biliary Cholangitis: Comparative Effects in a Multicentric Observational Study.
Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. [2023]Primary biliary cholangitis is a rare, chronic cholestatic liver disease characterized by the destruction of interlobular bile ducts, leading to cholestasis and liver fibrosis. Whether elafibranor, an oral, dual peroxisome proliferator-activated receptor (PPAR) α and δ agonist, may have benefit as a treatment for primary biliary cholangitis is unknown.