Obeticholic Acid for Biliary Atresia

No longer recruiting at 28 trial locations

Overseen By Scott Birnbaum

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Intercept Pharmaceuticals

Must not be taking: Anticoagulants

Disqualifiers: Liver transplant, BASM, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions 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 medication called Obeticholic Acid to determine its effectiveness for children with biliary atresia, a liver condition affecting bile flow, who have undergone successful hepatoportoenterostomy surgery. Researchers aim to assess the treatment's safety and effectiveness over time. Participants will receive either the medication or a placebo (a sugar pill) and will gradually increase their dose over several weeks. Children who have had biliary atresia surgery and maintain normal bilirubin levels (a liver function marker) may be suitable for this trial. As a Phase 2, Phase 3 trial, the study measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on anticoagulation therapy, you cannot participate in the trial.

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

Research has shown that obeticholic acid (OCA) has been tested for safety in people with biliary atresia, a liver condition. Early studies found that most participants tolerated OCA well, with no unusual or severe side effects. This suggests that OCA is generally safe for most people in these trials. In other studies where OCA was used for different liver issues, participants experienced a noticeable drop in serious liver problems compared to those who did not take OCA. This supports the idea that OCA is a well-tolerated treatment. However, like any treatment, some people might experience mild side effects, so monitoring participants during the trial is important. ^{1 2 3 4 5}

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

Researchers are excited about obeticholic acid (OCA) for biliary atresia because it represents a novel approach to treating this challenging condition. Unlike the standard treatments, which often involve surgical interventions like the Kasai procedure or liver transplantation, OCA works by targeting the farnesoid X receptor (FXR), a key regulator in bile acid metabolism. This unique mechanism may help reduce liver damage by improving bile flow and reducing inflammation. The potential for OCA to offer a less invasive treatment option with a direct impact on the disease process is what makes it stand out and fuels optimism in the medical community.

What evidence suggests that Obeticholic Acid might be an effective treatment for biliary atresia?

Previous studies have shown that obeticholic acid holds promise for treating liver-related conditions. This modified bile acid activates a specific receptor in the liver, aiding in bile and liver function and potentially reducing liver damage. Obeticholic acid is already approved for treating primary biliary cholangitis, a liver disease, suggesting it might also benefit those with biliary atresia. Early research in children with biliary atresia indicated it might improve liver function after surgery, but more studies are needed to confirm these benefits. In this trial, participants will receive either obeticholic acid or a matching placebo to further evaluate its effectiveness for biliary atresia. ^{1 3 5 6 7}

Who Is on the Research Team?

Lynda Szczech, MD

Principal Investigator

Intercept Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for children under 18 with non-syndromic biliary atresia who've had a successful hepatoportoenterostomy, indicated by bilirubin levels below 2 mg/dL. Children younger than 2 may join later, pending safety reviews.

Inclusion Criteria

I have been diagnosed with non-syndromic biliary atresia.

My bilirubin levels are below 2 mg/dL three months after my HPE procedure.

I am under 18 years old and may be eligible depending on safety reviews for those under 2.

Exclusion Criteria

GGT >500 Units per Liter (U/L)

Albumin <3.5 grams per deciliter (g/dL).

I am currently on blood thinner medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Titration

Participants receive OCA or placebo with dose titration every 2 weeks for the first 6 weeks

6 weeks

Age Expansion Treatment

Participants continue at the tolerated dose for approximately 24 months

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Obeticholic Acid

Trial Overview The study tests Obeticholic Acid (OCA) against a placebo in kids with biliary atresia post-hepatoportoenterostomy. It includes dose titration and age expansion phases to assess effectiveness and drug behavior in the body.

How Is the Trial Designed?

Group I: Participants receiving OCA Active Control 1 Intervention

Participants will be randomized to receive OCA (starting at 1.5 milligrams \[mg\] adult equivalent dose \[AED\]) orally, with water, once daily. Dose will be titrated every 2 weeks in a stepwise manner for the first 6 weeks, starting at 1.5 mg AED and titrating through 3 mg AED to a maximum of 5 mg AED, as tolerated; a discussion with the Medical Monitor is encouraged when determining uptitration if considerable signs or symptoms have arisen. Following the 6-week dose titration phase, participants will continue at the tolerated dose for approximately 24 months in Age Expansion Treatment Phase.

Group II: Participants receiving Matching placebo Placebo Group 1 Intervention

Participants will be randomized to receive matching placebo orally, with water, once daily. Dose will be titrated every 2 weeks in a stepwise manner for the first 6 weeks, starting at 1.5 mg AED and titrating through 3 mg AED to a maximum of 5 mg AED, as tolerated; a discussion with the Medical Monitor is encouraged when determining uptitration if considerable signs or symptoms have arisen. Following the 6-week dose titration phase, participants will continue at the tolerated dose for approximately 24 months in Age Expansion Treatment Phase.

Obeticholic Acid is already approved in United States, European Union for the following indications:

Approved in United States as Ocaliva for:

• Primary biliary cholangitis (PBC) without liver problems or with compensated cirrhosis but without portal hypertension

Approved in European Union as Ocaliva for:

• Primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA

Who Is Running the Clinical Trial?

Intercept Pharmaceuticals

Lead Sponsor

Trials

29

Recruited

16,600+

Published Research Related to This Trial

In a study of 457 patients with primary biliary cholangitis, obeticholic acid (OCA) showed a significant reduction in alkaline phosphatase levels by 29.5% after 12 months, while fibric acid derivatives achieved a higher reduction of 56.7%.

Despite the differences in alkaline phosphatase reduction, the overall biochemical response rates were similar between OCA (70.6%) and fibric acid treatments (80%), indicating that both therapies are effective second-line options for patients who do not respond adequately to ursodeoxycholic acid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UK-Wide Multicenter Evaluation of Second-line Therapies in Primary Biliary Cholangitis. Abbas, N., Culver, EL., Thorburn, D., et al.[2023]

Obeticholic acid (OCA) significantly reduced alkaline phosphatase (ALP) levels in patients with primary biliary cirrhosis who did not respond adequately to ursodeoxycholic acid, with reductions of 21%-25% compared to only 3% in the placebo group over 3 months.

The treatment was effective across all doses (10 mg, 25 mg, and 50 mg), but the 10 mg dose had the lowest incidence of pruritus, a common side effect, while maintaining significant biochemical improvements, which were sustained in a 12-month extension study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Hirschfield, GM., Mason, A., Luketic, V., et al.[2022]

In a real-world study of 120 patients with primary biliary cholangitis (PBC) who were not responding to ursodeoxycholic acid (UDCA), obeticholic acid (OCA) significantly improved liver function markers, including a notable decrease in alkaline phosphatase and ALT levels after one year of treatment.

OCA was well-tolerated, with a 35% rate of adverse events, but only 11.67% of patients discontinued treatment, primarily due to pruritus, indicating that it is a viable option for patients with PBC who have not responded to standard therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of obeticholic acid in a Southern European multicentre cohort of patients with primary biliary cholangitis and suboptimal response to ursodeoxycholic acid. Gomez, E., Garcia Buey, L., Molina, E., et al.[2021]

In a study involving cirrhotic rats, obeticholic acid (OCA) was found to have higher plasma and liver concentrations compared to control rats, indicating a potential risk for increased toxicity in cirrhotic conditions.

Despite having similar metabolic pathways to endogenous bile acids, OCA concentrations were significantly lower than those of natural bile acids, suggesting that OCA may be less cytotoxic than endogenous bile acids in this model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Profile of Obeticholic Acid and Endogenous Bile Acids in Rats with Decompensated Liver Cirrhosis. Roda, A., Aldini, R., Camborata, C., et al.[2018]

In a study involving 8 patients with primary biliary cholangitis (PBC) who were inadequately responding to ursodeoxycholic acid (UDCA), obeticholic acid (OCA) significantly improved the hepatic transport of bile acids, increasing their movement from blood into bile by 73%.

OCA treatment also reduced the time that hepatocytes were exposed to potentially harmful bile acids by about 30%, suggesting a protective mechanism against liver damage in PBC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obeticholic acid improves hepatic bile acid excretion in patients with primary biliary cholangitis. Kjærgaard, K., Frisch, K., Sørensen, M., et al.[2022]

Obeticholic acid (Ocaliva) is an FXR agonist that has received accelerated approval in the USA for treating primary biliary cholangitis, particularly in patients who do not respond adequately to ursodeoxycholic acid or cannot tolerate it.

The drug is currently in preregistration for the same indication in the EU, highlighting its potential as a significant treatment option for liver diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obeticholic Acid: First Global Approval. Markham, A., Keam, SJ.[2018]

In a study of 351 patients with primary biliary cholangitis, treatment with obeticholic acid (OCA) or fibrates significantly improved liver enzyme levels and the GLOBE score, indicating better liver health.

Adverse events occurred in 14.7% of patients, with the most common being pruritus, and treatment discontinuation was more frequent with fenofibrate due to intolerance, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obeticholic Acid and Fibrates in Primary Biliary Cholangitis: Comparative Effects in a Multicentric Observational Study. Reig, A., Álvarez-Navascués, C., Vergara, M., et al.[2021]

In a study of 191 patients with primary biliary cholangitis (PBC), obeticholic acid (OCA) demonstrated effectiveness, with a 42.9% response rate after 12 months, particularly in patients who did not have cirrhosis.

However, patients with cirrhosis experienced lower tolerability and a higher discontinuation rate (30% vs. 12%) due to adverse effects, primarily treatment-induced pruritus, highlighting the need for careful monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with obeticholic acid in patients with primary biliary cholangitis. D'Amato, D., De Vincentis, A., Malinverno, F., et al.[2022]

In a study of 100 cirrhotic patients with primary biliary cholangitis (PBC) treated with obeticholic acid (OCA), only about one-third achieved a biochemical response after 6 and 12 months, indicating limited efficacy in this population.

Key risk factors for serious adverse events (SAEs) during OCA therapy included high bilirubin levels (≥1.4 mg/dl), lower albumin levels, and a higher Child-Pugh score, suggesting that careful baseline assessments are essential to identify patients who may not safely benefit from OCA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of serious adverse events and non-response in cirrhotic patients with primary biliary cholangitis treated with obeticholic acid. De Vincentis, A., D'Amato, D., Cristoferi, L., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06121375

NCT06121375 | Study to Assess Efficacy, Safety, ... This study will evaluate the efficacy, safety and tolerability, as well as PK/PD of OCA in eligible pediatric participants with biliary atresia with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9614654/

Current and emerging adjuvant therapies in biliary atresia - PMC Obeticholic acid is a semi-synthetic bile acid that is a potent Farsenoid X receptor (FXR) agonist FDA-approved to treat UDCA-resistant primary biliary ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05321524?term=AREA%5BBasicSearch%5D(obeticholic%20acid)%20AND%20AREA%5BPhase%5D(PHASE2)&rank=8

Obeticholic Acid in Pediatric Subjects With Biliary Atresia The OLE will continue to evaluate safety, tolerability, pharmacodynamics, and efficacy of OCA. In addition, a change in vitamin A and D levels, and where ...

4. targetrwe.com targetrwe.com/research/news/intercept-announces-ocaliva-obeticholic-acid-data-in-pbc-to-be-presented-at-the-2016-aasld-annual-meeting/

Intercept Announces OCALIVA (OBETICHOLIC ACID) Data ... Obeticholic acid is also being investigated for patients with NASH and liver fibrosis, as well as primary sclerosing cholangitis and biliary atresia. About ...

5. ocalivahcp.com ocalivahcp.com/efficacy-long-term/

Long-Term Efficacy Data on OCALIVA® Review long-term efficacy data supporting OCALIVA® for appropriate adults with PBC. See safety and Full Prescribing Information, including Boxed WARNING.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06121375?cond=(Biliary%20Atresia)%20OR%20(bile%20duct%20atresia)&aggFilters=status:rec&viewType=Table&rank=3

Study to Assess Efficacy, Safety, Tolerability ... This study will evaluate the efficacy, safety and tolerability, as well as PK/PD of OCA in eligible pediatric participants with biliary atresia with ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39630028/

Hepatic real-world outcomes with obeticholic acid in ... We identified a 63% reduced risk of hospitalization for hepatic decompensation, liver transplant, or death in OCA-treated versus non-OCA-treated individuals.