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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of crofelemer, which may benefit individuals with Microvillus Inclusion Disease (MVID) who rely on parenteral support (intravenous nutrition). Participants will receive varying doses of crofelemer or a placebo to assess its efficacy and tolerability. The trial seeks participants with a confirmed MVID diagnosis who receive more than half of their hydration through intravenous support and can take medication orally or via a feeding tube. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that crofelemer is generally well-tolerated. The FDA has already approved it for treating diarrhea in adults caused by HIV or chemotherapy, indicating its well-established safety. Early studies have demonstrated that crofelemer can reduce the need for total parenteral nutrition (TPN) in individuals with rare conditions like Microvillus Inclusion Disease (MVID). In these studies, crofelemer helped patients without causing significant harm.

While specific side effects have not been detailed, ongoing research aims to confirm its safety in children with MVID. This trial is in an early stage and is still gathering information on how different doses of the drug are tolerated. However, its previous approval for other uses suggests that crofelemer is considered safe enough for testing in this new context. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for MVID?

Crofelemer is unique because it offers a new approach to managing Microvillus Inclusion Disease (MVID), a rare and severe intestinal disorder. Unlike existing treatments, which mainly focus on managing symptoms with nutritional support and medications to slow intestinal movement, crofelemer specifically targets the CFTR protein channel, which plays a role in fluid secretion in the gut. This mechanism helps reduce severe diarrhea by directly addressing the underlying cause rather than just the symptoms. Researchers are excited about crofelemer because it has the potential to significantly improve the quality of life for patients with MVID by offering a targeted, effective treatment option.

What evidence suggests that crofelemer might be an effective treatment for Microvillus Inclusion Disease?

Research has shown that crofelemer can significantly reduce the need for total parenteral nutrition (TPN) in patients with Microvillus Inclusion Disease (MVID). One study found that crofelemer decreased the need for TPN by up to 27% in patients with intestinal issues like MVID. As a result, patients required less nutritional support through an IV, potentially enhancing their quality of life. Crofelemer reduces fluid release in the intestines, helping to manage MVID symptoms. Early findings suggest that this treatment may effectively lessen symptom severity for those with this rare condition. Participants in this trial will receive different dosages of crofelemer or a placebo to further evaluate its effectiveness. ^{1 3 6 7 8}

Who Is on the Research Team?

Lissette Jimenez, MD, MPH

Principal Investigator

Boston Children's Hospital

Pravin Chaturvedi, PhD

Principal Investigator

Napo Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

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.

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

I have had an organ transplant.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. jaguarhealth.gcs-web.com jaguarhealth.gcs-web.com/news-releases/news-release-details/proof-concept-results-show-crofelemer-reduced-total-parenteral

Proof-of-Concept Results Show Crofelemer Reduced Total ... Proof-of-concept results show Crofelemer reduced total parenteral nutrition in patients with rare diseases Microvillus Inclusion Disease (MVID) and Short Bowel ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06721871

NCT06721871 | Ascending Doses of Crofelemer Powder ... a 32-week study that will evaluate the safety, tolerability and preliminary efficacy of multiple ascending doses of crofelemer, compared to placebo, ...

3. finance.yahoo.com finance.yahoo.com/news/proof-concept-results-show-crofelemer-121500654.html

Proof-of-Concept Results Show Crofelemer Reduced Total ... Proof-of-Concept Results Show Crofelemer Reduced Total Parenteral Nutrition in Patients with Rare Diseases Microvillus Inclusion Disease (MVID) ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9900906/

Therapy Development for Microvillus Inclusion Disease using ... Crofelemer was also able to inhibit maximally stimulated fluid secretion significantly, but incompletely in enteroids. Fluid management of MVID patients is a ...

5. biospace.com biospace.com/press-releases/jaguar-health-provides-updates-on-orphan-disease-intestinal-failure-development-program-for-crofelemer

Jaguar Health Provides Updates on Orphan Disease ... Crofelemer reduced the required total parenteral nutrition in patients with intestinal failure due to MVID and short bowel syndrome by up to 27% and 12.5% ...

6. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-crofelemer-for-children-with-microvillus-inclusion-disease-mvid/

Study on the Safety and Effectiveness of Crofelemer ... This clinical trial tests the safety and effectiveness of Crofelemer, an oral solution, in treating children with Microvillus Inclusion Disease, ...

7. answers.childrenshospital.org answers.childrenshospital.org/microvillus-inclusion-disease-organoids/

Microvillus inclusion disease: From organoids to new treatments Currently, crofelemer is approved for adult diarrhea caused by HIV or chemotherapy. However, the team recently obtained FDA permission to ...

8. biospace.com biospace.com/press-releases/first-patient-randomized-in-jaguar-healths-phase-2-randomized-double-blind-placebo-controlled-clinical-trial-of-crofelemer-in-pediatric-patients-with-microvillus-inclusion-disease-mvid

First Patient Randomized in Jaguar Health's Phase 2 ... Patients with MVID suffer from devastating diarrhea and dehydration caused by this debilitating, lifelong condition. ... While crucial for MVID ...