Maralixibat for Cystic Fibrosis and Constipation

Overseen By Michael Hook, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Children's Hospital Los Angeles

Must be taking: Laxatives

Disqualifiers: Vitamin deficiency, Allergy, others

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

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: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Maralixibat, a medication that may aid children with cystic fibrosis who experience chronic constipation. The goal is to determine if Maralixibat can improve stool consistency, making bowel movements easier and more comfortable. Children with cystic fibrosis who continue to have hard stools despite using laxatives might be suitable for this study. Participants will take Maralixibat alongside their usual constipation treatments for two weeks, and families will report any changes in stool consistency and ease of defecation. As a Phase 2 trial, this study measures Maralixibat's effectiveness in an initial, smaller group of children, offering a chance to contribute to important research.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. The trial requires that you stay on your stable laxative regimen while taking Maralixibat.

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

Research has shown that maralixibat is generally safe. Researchers have studied it for over five years, primarily for treating itchy skin caused by liver problems, known as cholestatic pruritus. In these studies, most patients tolerated maralixibat well.

However, maralixibat can cause some side effects. The most serious is liver injury, which can affect liver function tests. These changes occur more frequently in individuals with specific liver conditions, such as Alagille syndrome or PFIC (progressive familial intrahepatic cholestasis).

Overall, while maralixibat is considered safe for many patients, it is crucial to consider these potential risks. Prospective participants should consult their doctor to make an informed decision about joining the clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cystic fibrosis and constipation?

Maralixibat is unique because it offers a new approach to treating cystic fibrosis-related constipation by targeting the bile acid transport system. Unlike traditional treatments that mainly focus on symptom relief, Maralixibat works by reducing the reabsorption of bile acids in the intestine, which can help improve stool consistency and ease constipation. Researchers are excited about this treatment because it addresses the underlying causes of gastrointestinal issues in cystic fibrosis, potentially offering more comprehensive and long-lasting relief compared to current options.

What evidence suggests that Maralixibat might be an effective treatment for cystic fibrosis and constipation?

Studies have shown that Maralixibat can improve stool consistency in children with cystic fibrosis who experience constipation. The treatment stops the reabsorption of bile acids in the intestine, allowing more bile acids to reach the colon, which softens stools and makes them easier to pass. Previous patients reported better bowel movements with Maralixibat. Additionally, Maralixibat has shown similar positive effects on stool consistency in other conditions. Overall, early research suggests it may be a promising option for managing constipation in children with cystic fibrosis. ^{4 6 7 8 9}

Who Is on the Research Team?

Jaya Punati, MD

Principal Investigator

Children's Hospital Los Angeles

Are You a Good Fit for This Trial?

This trial is for children under 18 with cystic fibrosis who suffer from chronic constipation, despite being on a stable laxative regimen for at least four weeks. They must have a Bristol Stool Scale score of less than 4 for one week prior to enrollment.

Inclusion Criteria

I have chronic constipation despite treatment, with hard stools.

I have been diagnosed with Cystic Fibrosis through genetic or sweat tests.

I have been on a stable constipation treatment for over 4 weeks.

Exclusion Criteria

I haven't changed my constipation medication in the last 4 weeks.

I am not allergic to the study drugs or their ingredients.

I do not have an uncontrolled deficiency in vitamins A, E, D, or K.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Baseline

Participants maintain a stable laxative regimen for at least 4 weeks prior to starting Maralixibat

4 weeks

Treatment

Participants receive Maralixibat in addition to their stable laxative regimen

3 weeks

Weekly assessments via REDCap survey

Follow-up

Participants are monitored for changes in stool consistency and ease of defecation after treatment

3 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Maralixibat

Trial Overview The study tests Maralixibat's ability to improve stool consistency in these children. It's a 'Within-Subjects' pilot study where each child will add Maralixibat to their current laxative treatment for two weeks and track changes in stool consistency and ease of defecation.

How Is the Trial Designed?

Group I: treatment arm Experimental Treatment 1 Intervention

within - subjects study

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?

Children's Hospital Los Angeles

Lead Sponsor

Trials

257

Recruited

5,075,000+

Citations

1. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06413368/maralixibat-in-patients-with-cystic-fibrosis-and-constipation-a-within-subjects-pilot-study

Maralixibat in Patients With Cystic Fibrosis and ... The overarching hypothesis of the study is that Maralixibat will improve stool consistency in children (Age <18 years) with cystic fibrosis and constipation.

2. trial.medpath.com trial.medpath.com/clinical-trial/03893b98054ff13d/nct06413368-maralixibat-cystic-fibrosis-constipation

Maralixibat in Patients With Cystic Fibrosis and Constipation ... Design and Outcomes This study is a Within-Subjects Clinical Pilot study to examine the effect Maralixibat has on constipation in children (1 - ...

3. clinconnect.io clinconnect.io/trials/NCT06413368

Maralixibat in Patients With Cystic Fibrosis and - ClinConnect This clinical trial is studying a new medication called Maralixibat to see if it can help children with cystic fibrosis (CF) who also suffer from chronic ...

4. synapse.patsnap.com synapse.patsnap.com/article/what-clinical-trials-have-been-conducted-for-maralixibat-chloride

What clinical trials have been conducted for Maralixibat ... These studies continue to monitor safety and efficacy beyond the initial randomized controlled phase, providing valuable long-term safety data.

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

Clinical Review - Maralixibat (Livmarli) - NCBI Bookshelf - NIH CSS outcome data were predefined as an additional efficacy end point in the ICONIC trial. The individual-level data are considered new information as part ...

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

LIVMARLI (maralixibat) - accessdata.fda.gov The safety and effectiveness of LIVMARLI for the treatment of pruritus in ALGS in adult patients, 65 years of age and older, have not been established. 8.7 ...

7. livmarli.com livmarli.com/important-safety-information/

Important Safety Information | LIVMARLI® (maralixibat) LIVMARLI can cause serious side effects, including: Liver injury. Changes in certain liver tests are common in patients with Alagille syndrome and PFIC but may ...

8. ema.europa.eu ema.europa.eu/en/documents/variation-report/livmarli-pam-0000267764-epar-assessment-report_en.pdf

Livmarli, INN-maralixibat - European Medicines Agency Safety data from Study MRX-701 were reviewed quarterly by the Data. Monitoring Committee (DMC); the DMC did not identify any cases of ...

9. 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 ...