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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Chronic constipation is a feature of children with cystic fibrosis (CF). This is postulated to be a result of inhibition of secretory activity of the gastrointestinal luminal cells due to ineffective chloride channel function. Typical laxatives that work as osmotic agents fail to produce adequate relief in this population. Maralixibat is a non-systemic bile acid transport inhibitor (IBATi) that acts by interrupting bile acid reabsorption in the ileum thus interrupting the normal enterohepatic circulation. This interruption results in a larger volume of bile acids reaching the colon and being excreted in stool. Bile acids are known to decrease bowel transit time, increase mucosal permeability and secretions, as well as alter gut microbiota resulting in diarrhea. The overarching hypothesis of the study is that Maralixibat will improve stool consistency in children (Age \<18 years) with cystic fibrosis and constipation (Bristol Stool Scale \<4). Specifically, we aim to test the hypothesis that IBATi improves the consistency of stool to Bristol scale \>4 in children with CF and constipation. We will recruit a total of 20 patients with CF and constipation (defined as Bristol Stool Scale \<4 for 1 week prior to enrollment while on a stable laxative regimen for at least 4 weeks.) Design is a 'Within-Subjects' study by which each enrolled patient will take Maralixibat for 2 weeks total in addition to their stable laxative regimen during the study. Stool consistency \& ease of defecation will be recorded before and during the study period by families of enrolled patients via materials provided by the investigators. Stool consistency and ease of defecation will be compared before and after initiation of Maralixibat. The primary endpoint: Improvement in stool consistency to Bristol scale \>4 in children with CF and constipation. The secondary endpoint: Improvement in ease of defecation in children with CF and constipation. This will be measured via survey using a standardized scale (Bristol Stool Scale) and questionnaires developed by the research team. Analysis will involve comparison of pre-intervention to post-intervention stool consistency \& survey

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.

Research Team

Jaya Punati, MD

Principal Investigator

Children's Hospital Los Angeles

Eligibility Criteria

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 am between 1 and 18 years old.

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

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

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

Treatment Details

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.

Participant Groups

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+