Maralixibat for Itching in Liver Disease

Recruiting at 38 trial locations

Overseen By Clinical Trials Mirum

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Mirum Pharmaceuticals, Inc.

Must be taking: Antipruritics, Ursodeoxycholic acid

Must not be taking: IBAT inhibitors

Disqualifiers: ALGS, ICP, PBC, PFIC, PSC, others

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: 20

Duration: 40 weeks

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether maralixibat, an investigational treatment, is safe and effective for people with cholestatic liver disease who experience severe, ongoing itching (pruritus) unrelieved by other treatments. Participants will receive either maralixibat or a placebo, and the trial will assess how well the treatment eases itching. This trial may suit those with abnormal liver tests for over 90 days who still experience itching despite other medications. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially bringing a new treatment to market.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications if you are on antipruritics or ursodeoxycholic acid, as long as you have been on a stable dose for at least 30 days before the screening and continue this dosing during the study.

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

Research has shown that maralixibat is generally safe for individuals with certain liver diseases. More than 280 patients, aged 1 month to 24 years, have used this treatment without major issues. Maralixibat is already approved in other countries to help with itching in people with liver problems, suggesting its safety for similar conditions.

Over five years of safety data indicate potential side effects, which are usually mild. Monitoring any changes and reporting them to the study team is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for liver disease with itching?

Maralixibat is unique because it targets the root cause of itching in liver disease by inhibiting a protein that affects bile acid levels in the body, which is different from most treatments that only manage symptoms. Unlike standard treatments like antihistamines or bile acid binders, Maralixibat is an oral solution that directly reduces bile acid buildup, potentially offering more effective relief from itching. Researchers are excited about its novel mechanism of action and the potential for faster symptom relief compared to current options.

What evidence suggests that maralixibat might be an effective treatment for itching in liver disease?

Research has shown that maralixibat can reduce itching caused by cholestatic liver disease, which occurs when bile flow from the liver slows or becomes blocked. Studies have found that maralixibat lowers bile acid levels in the blood, which correlates with reduced itching. In patients with Alagille syndrome, a type of liver disease, maralixibat improved symptoms such as itching and overall liver function. This treatment has effectively increased patient comfort and quality of life. Overall, maralixibat shows promise for those who have not found relief with other treatments. Participants in this trial will receive either maralixibat or a placebo, with the option to switch to maralixibat after 20 weeks. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for children and adults with cholestatic liver disease who suffer from severe itching that hasn't improved with other treatments. Participants must have no remaining treatment options available to them.

Inclusion Criteria

I can read and understand questionnaires.

I have been on a stable dose of medication for itching or ursodeoxycholic acid for the last 30 days.

Informed consent and assent (as applicable)

Exclusion Criteria

Unstable and/or serious medical disease that is likely to impair the ability to participate in all aspects of the study, confound efficacy and/or safety assessments, or result in substantially shortened life expectancy (e.g., any active malignancy including hematological malignancy, end-stage heart failure, active infection, acute and chronic diarrhea). Exceptionally, previous history of malignancy, adequately treated/in remission, that in opinion of investigator and medical monitor does not impact participant safety and participation in the study, may be allowed

Known intolerance/hypersensitivity to maralixibat or its excipients

I have had skin itching or atopic dermatitis in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive maralixibat or placebo for up to 20 weeks, followed by maralixibat for an additional 20 weeks

40 weeks

Weekly visits for the first 20 weeks, then bi-weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Maralixibat

Trial Overview The study is testing the safety and effectiveness of a drug called Maralixibat compared to a placebo in reducing itchiness associated with cholestatic liver disease.

How Is the Trial Designed?

Group I: Maralixibat Experimental Treatment 1 Intervention

Participants will receive maralixibat oral solution 300 μg/kg orally once daily for 1 week and then twice daily for 39 weeks.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive placebo matched to maralixibat oral solution orally once daily for 1 week and then twice daily for 19 weeks. After 20 weeks, participants will receive maralixibat oral solution 300 μg/kg orally once daily for 1 week and then twice daily for 19 weeks.

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+

Published Research Related to This Trial

In a study of 309 Indonesian children aged 0.6 to 6.6 years, vitamin A supplementation significantly improved vitamin A status, while treatment for intestinal helminths (ascariasis) did not show a significant effect on vitamin A levels.

The modified relative dose response (MRDR) test was more effective than serum retinol concentrations in assessing the impact of treatments on vitamin A status, highlighting its utility in evaluating nutritional interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin A status of Indonesian children infected with Ascaris lumbricoides after dosing with vitamin A supplements and albendazole. Tanumihardjo, SA., Permaesih, D., Muherdiyantiningsih, ., et al.[2018]

In a study of 16 African patients with W. bancrofti filariasis, treatment with levamisole led to a rapid decrease in microfilaria levels starting from the first day, demonstrating its efficacy in managing the infection.

By the end of the treatment, 87.5% of patients became microfilaria-negative, while the remaining 12.5% showed significant reductions in their microfilaria concentrations, indicating that levamisole can be an effective option even for patients with persistent low microfilaremia after previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of levamisole in W. bancrofti filariasis]. Pérez Avila, J., Lastre González, M., Lazo Lopetegui, O., et al.[2016]

Levamisole is highly effective for treating ascariasis, with single doses of 50 to 150 mg eliminating 90 to 100% of parasites without significant side effects.

While levamisole shows some activity against hookworms and microfilariae of certain filarial infections, it is less effective than other treatments like diethylcarbamazine, and further research is needed to establish its efficacy against these and other parasites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of levamisole in parasitic infections. Miller, MJ.[2018]

In a study comparing treatment regimens for bancroftian filariasis, the combination of ivermectin and albendazole (IA) was found to be more effective in completely clearing microfilariae compared to either dose of albendazole alone, with IA achieving a clearance rate of 79%.

Repeated semiannual treatment with albendazole alone was shown to be safe and effective, leading to significant reductions in microfilariae counts, making it a viable option for mass drug administration in areas where ivermectin cannot be used due to safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semiannual Treatment of Albendazole Alone is Efficacious for Treatment of Lymphatic Filariasis: A Randomized Open-label Trial in Cote d'Ivoire. Ouattara, AF., Bjerum, CM., Aboulaye, M., et al.[2022]

In a study involving 57 children with severe cholestasis due to Alagille Syndrome, maralixibat significantly improved symptoms of itching (pruritus) and quality of life after 48 weeks of treatment, with notable statistical improvements in both measures.

While maralixibat showed benefits in reducing pruritus and enhancing quality of life, some participants experienced treatment-emergent adverse events, particularly increases in liver enzymes, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of long-term administration of maralixibat on children with cholestasis secondary to Alagille syndrome. Shneider, BL., Spino, CA., Kamath, BM., et al.[2023]

Levamisole significantly reduced the microfilaria rate and density of Wuchereria bancrofti when administered at 3 mg/kg daily for 8 days, but the microfilaria rate increased back to near pre-treatment levels shortly after treatment ended.

Diethylcarbamazine (DEC) was found to be more effective than both levamisole and mebendazole in reducing microfilaria rates and densities, suggesting it is a better treatment option for this infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levamisole and mebendazole in the treatment of bancroftian infection. Narasimham, MV., Roychowdhury, SP., Das, M., et al.[2013]

In a phase 2 study involving 66 adults with primary biliary cholangitis (PBC) and pruritus, maralixibat did not show a significant difference in reducing itching compared to placebo, indicating that its efficacy may be limited in this context.

Both treatment groups experienced high rates of adverse events, particularly gastrointestinal disorders, suggesting that while maralixibat is being explored as a treatment option, its safety profile needs careful consideration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Controlled, Phase 2 Study of Maralixibat in the Treatment of Itching Associated With Primary Biliary Cholangitis. Mayo, MJ., Pockros, PJ., Jones, D., et al.[2021]

Maralixibat is the first FDA-approved treatment specifically for cholestatic pruritus in children with Alagille syndrome, showing significant efficacy in clinical trials with follow-up of up to 4 years.

A case report highlights a patient who experienced complete resolution of pruritus for over 7 years after starting maralixibat, allowing her to stop all other antipruritic medications, demonstrating the long-term effectiveness of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resolution of Pruritus in a Child With Alagille Syndrome Treated With Maralixibat for Seven Years: Durable Response and Discontinuation of Other Medications. Garcia, A., Hsu, E., Lin, HC.[2023]

In a multicenter trial involving 37 children with Alagille syndrome, maralixibat showed potential to reduce severe itching (pruritus) compared to placebo, particularly at doses of 70 and 140 µg/kg/day, with significant caregiver and clinician-reported improvements.

The treatment was found to be safe, with no significant changes in liver function or bile acid levels, and adverse events were similar between maralixibat and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-Controlled Randomized Trial of an Intestinal Bile Salt Transport Inhibitor for Pruritus in Alagille Syndrome. Shneider, BL., Spino, C., Kamath, BM., et al.[2023]

Maralixibat (Livmarli™) is an oral medication that works as an ileal bile acid transporter (IBAT) inhibitor, specifically developed for treating rare cholestatic liver diseases like Alagille syndrome (ALGS).

It received its first approval in the USA on September 29, 2021, for treating cholestatic pruritus in patients with ALGS aged 1 year and older, and is currently under review in Europe and being studied for younger patients and other liver disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maralixibat: First Approval. Shirley, M.[2022]

Citations

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

Clinical Review - Maralixibat (Livmarli) - NCBI Bookshelf - NIH Finally, the experts stated that between 50% and 75% of patients with cholestatic liver disease will require a liver transplant and that cholestatic pruritus is ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02160782

NCT02160782 | Safety and Efficacy Study of LUM001 ... Intractable pruritus explainable only by liver disease. Females of ... Note: 400 mcg/kg maralixibat chloride is equivalent to 380 mcg/kg free maralixibat.

3. ema.europa.eu ema.europa.eu/en/documents/variation-report/livmarli-h-c-005857-ii-0003-g-epar-assessment-report-variation_en.pdf

Livmarli, INN-maralixibat - European Medicines Agency SBD leads to improvement in pruritus and growth, liver histology, and better disease outcomes with longer NLS (Kurbegov et al. 2003; Arnell ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/214662s000lbl.pdf

LIVMARLI (maralixibat) - accessdata.fda.gov Clinical studies of LIVMARLI included ALGS patients with impaired hepatic function at baseline. The efficacy and safety in ALGS patients with clinically ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/liv.16201

Maralixibat Reduces Serum Bile Acids and Improves ... Maralixibat Reduces Serum Bile Acids and Improves Cholestatic Pruritus in Adolescents With Alagille Syndrome · 1 Introduction. Alagille syndrome ...

6. ema.europa.eu ema.europa.eu/en/documents/product-information/livmarli-epar-product-information_en.pdf

Livmarli, INN-maralixibat - European Medicines Agency Summary of the safety profile. Over 280 patients with cholestatic liver diseases aged 1 month to 24 years have been treated with maralixibat ...

7. livmarlihcp.com livmarlihcp.com/alagille-syndrome-cholestatic-pruritus/safety/

Safety Profile | LIVMARLI® (maralixibat) | HCP Backed by >5 years of safety data,* LIVMARLI has a well-characterized safety and tolerability profile for cholestatic pruritus in patients with Alagille ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02160782

NCT02160782 | Safety and Efficacy Study of LUM001 ... Intractable pruritus explainable only by liver disease. Females of childbearing potential must have a negative serum pregnancy test during Screening. Males ...