Crofelemer for Microvillus Inclusion Disease

Recruiting at 2 trial locations

Overseen By Sara Papetti, MA

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Napo Pharmaceuticals, Inc.

Must not be taking: Diuretics, IV antibiotics, Anti-diarrheals

Disqualifiers: Organ transplant, Malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have started any new anti-diarrheal drugs in the last 4 weeks, you may not be eligible to participate.

What data supports the effectiveness of the drug Crofelemer for treating Microvillus Inclusion Disease?

Crofelemer has been shown to improve bowel function in conditions with secretory diarrhea, which suggests it might help with similar symptoms in Microvillus Inclusion Disease. ^{1 2 3 4 5}

What is the purpose of this trial?

a 32-week study that will evaluate the safety, tolerability and preliminary efficacy of multiple ascending doses of crofelemer, compared to placebo, using a randomized cross-over design within each dose level, when administered to participants with MVID receiving parenteral support (PS, defined as TPN with or without supplementary IV fluid requirements). Blinded study drug will be administered as a novel crofelemer formulation, Crofelemer Powder for Oral Solution, or a matching placebo powder formulation for oral solution. Assigned study drug will be reconstituted and administered orally (or enterally) three times daily (TID) as a concentrated liquid formulation in each of the three dose levels

Research Team

Pravin Chaturvedi, PhD

Principal Investigator

Napo Pharmaceuticals, Inc.

Lissette Jimenez, MD, MPH

Principal Investigator

Boston Children's Hospital

Eligibility Criteria

This trial is for children with Microvillus Inclusion Disease (MVID) who rely on parenteral support, like total parenteral nutrition (TPN). Participants should be able to take the study drug orally or enterally three times a day. Specific details about who can't join are not provided.

Inclusion Criteria

Half of my weekly fluid needs were met through parenteral support in the last 2 months.

I can take medicine that is mixed into a liquid.

I agree to use contraception or practice abstinence.

Exclusion Criteria

I haven't had an infection needing IV antibiotics in the last month.

I have had an organ transplant.

Increase in ALT, AST, or total bilirubin ≥2 times usual values within the last 4 weeks

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple ascending doses of crofelemer or placebo in a randomized cross-over design over three dose levels

24 weeks

Regular visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• Crofelemer

Trial Overview The trial tests Crofelemer Powder versus a placebo in kids with MVID over 32 weeks. It's designed to see if it's safe and might work to help their condition. Patients will switch between Crofelemer and placebo at different stages so each child gets both treatments at some point.

Participant Groups

Group I: Dose Level 3/Treatment Period 2: 10mg/kg/dose 3x/day Experimental Treatment 1 Intervention

Participants will crossover to either crofelemer powder for oral solution or placebo comparator

Group II: Dose Level 3/Treatment Period 1: 10mg/kg/dose 3x/day Experimental Treatment 1 Intervention

Participants will crossover to either crofelemer powder for oral solution or placebo comparator or continue on crofelemer powder for oral solution or the placebo comparator that they were previously on during Dose Level 2 (1 month duration)

Group III: Dose Level 2/Treatment Period 2: 3mg/kg/dose 3x/day Experimental Treatment 1 Intervention

Participants will crossover to either crofelemer powder for oral solution or placebo comparator

Group IV: Dose Level 2/Treatment Period 1: 3mg/kg/dose 3x/day Experimental Treatment 1 Intervention

Participants will crossover to either crofelemer powder for oral solution or placebo comparator or continue on crofelemer powder for oral solution or the placebo comparator that they were previously on during Dose Level 1 (1 month duration)

Group V: Dose Level 1/Treatment Period 2: 1mg/kg/dose 3x/day Experimental Treatment 1 Intervention

Participants will crossover to either crofelemer powder for oral solution or placebo comparator

Group VI: Dose Level 1/Treatment Period 1: 1mg/kg/dose 3x/day Experimental Treatment 1 Intervention

Participants may be randomized to crofelemer powder for oral solution during Treatment Period 1 (1 month duration)

Group VII: Dose Level 1/Treatment Period 1: Placebo 3x/day Placebo Group 1 Intervention

Participants may be randomized to the placebo comparator during Treatment Period 1 (1 month duration)

Group VIII: Dose Level 2/Treatment Period 1: Placebo 3x/day Placebo Group 1 Intervention

Participants will crossover to either crofelemer powder for oral solution or placebo comparator or continue on crofelemer powder for oral solution or the placebo comparator that they were previously on during Dose Level 1 (1 month duration)

Group IX: Dose Level 2/Treatment Period 2: Placebo 3x/day Placebo Group 1 Intervention

Participants will crossover to either crofelemer powder for oral solution or placebo comparator

Group X: Dose Level 3/Treatment Period 1: Placebo 3x/day Placebo Group 1 Intervention

Participants will crossover to either crofelemer powder for oral solution or placebo comparator or continue on crofelemer powder for oral solutionor the placebo comparator that they were previously on during Dose Level 2 (1 month duration)

Group XI: Dose Level 3/Treatment Period 2: Placebo 3x/day Placebo Group 1 Intervention

Participants will crossover to either crofelemer powder for oral solution or placebo comparator

Group XII: Dose Level 1/Treatment Period 2: Placebo 3x/day Placebo Group 1 Intervention

Participants will crossover to either crofelemer powder for oral solution or placebo comparator

Who Is Running the Clinical Trial?

Napo Pharmaceuticals, Inc.

Lead Sponsor

Trials

6

Recruited

470+

Findings from Research

In a study comparing liquid diet therapy (LDT) in children with active Crohn's disease, whole-protein polymeric formula (PF) did not significantly improve adherence compared to amino acid-based elemental formula (EF), with completion rates of 58% for PF and 72% for EF.

However, PF was associated with a significantly lower need for nasogastric tube administration (31% for PF vs. 55% for EF), suggesting it may be easier to consume despite similar remission rates between the two formulas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does polymeric formula improve adherence to liquid diet therapy in children with active Crohn's disease? Rodrigues, AF., Johnson, T., Davies, P., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

A double-blind clinical trial for treatment of Crohn's disease by oral administration of Alequel, a mixture of autologous colon-extracted proteins: a patient-tailored approach. [2017]

2. England pubmed.ncbi.nlm.nih.gov

Enteral feeding therapy for newly diagnosed pediatric Crohn's disease: a double-blind randomized controlled trial with two years follow-up. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of crofelemer in the treatment of diarrhea-predominant irritable bowel syndrome patients. [2016]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Folic acid-modified lactoferrin nanoparticles coated with a laminarin layer loaded curcumin with dual-targeting for ulcerative colitis treatment. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Does polymeric formula improve adherence to liquid diet therapy in children with active Crohn's disease? [2018]