Maralixibat for Cholestasis

No longer recruiting at 33 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Mirum Pharmaceuticals, Inc.

Disqualifiers: Pregnancy, Lactation, Non-compliance, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Long-term

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on understanding the long-term safety of maralixibat, a treatment for cholestasis, a condition affecting bile flow in the liver. All participants will take maralixibat as an oral solution. Those who completed a previous study with maralixibat without serious issues may be suitable candidates for this trial. The goal is to assess patient tolerance to the treatment over time. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Do I have to stop taking my current medications for the trial?

The trial information does not clearly state if you need to stop taking your current medications. However, it mentions that certain medications are prohibited between specific visits, so it's best to discuss your current medications with the study team.

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

Research has shown that maralixibat is usually easy for patients to handle. Studies have found it can lower bile acid levels in the blood, aiding conditions like PFIC, a liver disease. The FDA has approved maralixibat, also known as LIVMARLI, to treat itching in children with PFIC, indicating it has passed safety checks for this use.

Some side effects, such as diarrhea and stomach pain, have been reported, but they are usually mild. Most patients manage the treatment without major problems. However, since each body can react differently, discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for cholestasis focus on managing symptoms through medications like ursodeoxycholic acid to improve bile flow or corticosteroids to reduce inflammation. But Maralixibat works differently by targeting and inhibiting the apical sodium-dependent bile acid transporter (ASBT), which reduces the reabsorption of bile acids in the intestines. This novel mechanism of action helps lower toxic bile acid levels in the liver, potentially offering a more direct approach to addressing the root cause of cholestasis. Researchers are excited about Maralixibat because it has shown promise in not only reducing bile acid levels but also in improving liver function and overall quality of life for patients with this condition.

What evidence suggests that maralixibat might be an effective treatment for cholestasis?

Research has shown that maralixibat effectively treats liver diseases that cause bile buildup. It prevents bile acids from being reabsorbed, lowering their levels in the blood. This reduction helps alleviate itching, a common symptom of these conditions. Patients using maralixibat experienced a significant drop in bile acid levels compared to those who did not use it. Studies have confirmed its effectiveness and safety for treating itching in children with certain liver diseases. These findings suggest that maralixibat may be helpful in managing these liver problems. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for patients with Progressive Familial Intrahepatic Cholestasis who have completed the MRX-502 study. They must be able to give informed consent and not have any health issues or lab results that could make the trial unsafe for them. Pregnant or breastfeeding women, those planning pregnancy, or anyone with a history of non-compliance in the previous study cannot participate.

Inclusion Criteria

Provide informed consent and assent (as applicable) per Institutional Review Board/Ethics Committee (IRB/EC)

Completion of study MRX-502

Exclusion Criteria

I stopped taking maralixibat due to a serious side effect in the MRX-502 study.

I have always followed medical advice and participated reliably in past studies.

You have any other medical conditions or abnormal test results that could make it unsafe for you to participate in the study or affect your ability to complete it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Maralixibat oral solution

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive Maralixibat to evaluate long-term safety and efficacy

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Maralixibat

Trial Overview The trial is testing Maralixibat's long-term safety and effectiveness in treating cholestasis conditions like PFIC. It's an open label extension, meaning everyone knows they're getting Maralixibat and there’s no placebo group.

How Is the Trial Designed?

Group I: Maralixibat Experimental Treatment 1 Intervention

All subjects will receive Maralixibat oral solution

Maralixibat is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Livmarli for:

• Treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) 1 year of age and older
• Treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) 3 months of age and older

Approved in European Union as Livmarli for:

• Treatment of cholestatic pruritus in patients with Alagille syndrome

Approved in Canada as Livmarli for:

• Treatment of cholestatic pruritus in adults with Alagille syndrome

Who Is Running the Clinical Trial?

Mirum Pharmaceuticals, Inc.

Lead Sponsor

Trials

32

Recruited

102,000+

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK608449/

Clinical Review - Maralixibat (Livmarli) - NCBI Bookshelf - NIH Maralixibat (Livmarli), 9.5 mg/mL, oral solution, for the treatment of cholestatic pruritus in patients with ALGS aged 2 months and older.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8748361/

Maralixibat: First Approval - PMC In cholestatic liver diseases, maralixibat acts through the inhibition of the IBAT, resulting in decreased reabsorption of bile acids (primarily ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02057718

NCT02057718 | Open Label Study to Evaluate Efficacy and ... Open Label Study to Evaluate Efficacy and Long Term Safety of LUM001 (Maralixibat) in the Treatment of Cholestatic Liver Disease in Patients With Progressive ...

4. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/livmarli

Livmarli | European Medicines Agency (EMA) Results showed that patients on Livmarli had a reduction in the level of bile acid in their blood, whereas bile acid levels did not change in patients given ...

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/214662s011lbl.pdf

LIVMARLI® (maralixibat) oral solution - accessdata.fda.gov The safety and effectiveness of LIVMARLI for the treatment of cholestatic pruritus in PFIC have been established in pediatric patients aged 12 months of age ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02160782

NCT02160782 | Safety and Efficacy Study of LUM001 ... Evidence of cholestasis (one or more of the following):. Total serum bile acid > 3x ULN for age. Conjugated bilirubin > 1 mg/dL. Fat soluble vitamin deficiency ...

7. link.springer.com link.springer.com/article/10.1007/s40265-021-01649-0

Maralixibat: First Approval | Drugs In cholestatic liver diseases, maralixibat acts through the inhibition of the IBAT, resulting in decreased reabsorption of bile acids (primarily ...