Ascending Doses of Crofelemer Powder for Oral Solution in Pediatric Microvillus Inclusion Disease (MVID)

Phase 2

Not yet recruiting

• Conditions: Microvillus Inclusion Disease; Congenital Disorders; Rare Diseases
• Interventions: Drug: Crofelemer Powder for Oral Solution; Drug: Placebo Powder for Oral Solution

• Registration Number: NCT06721871
• Lead Sponsor: Napo Pharmaceuticals, Inc.

Brief Summary

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

Detailed Description

This is a randomized, double-blind, placebo-controlled, dose-escalating study with a placebo cross-over design within each dose level in this ultra-rare MVID participant population. For the primary objective, safety and tolerability, comparisons between the crofelemer and placebo within each dose level and over 24 weeks with all 3 dose levels combined will be descriptively summarized. For secondary objectives, changes from the 8-week pre-treatment Baseline Period will be made: 1) within each participant between crofelemer and placebo within each dose level, 2) within each participant between crofelemer and placebo through 24 weeks, 3) between the crofelemer and placebo groups (if multiple participants per group are enrolled) within each dose level, and 4) between the crofelemer and placebo groups (if multiple participants per group are enrolled) through 24 weeks.

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2024-11-20
• Study First Submitted QC: 2024-12-03
• Study First Posted: 2024-12-06
• Last Update Submitted: 2025-03-28
• Last Update Posted: 2025-03-30
• Study Start: 2025-04-15
• Primary Completion: 2025-12
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Participants (assent for participants older than 7 years of age) and/or their legal parent/guardian sign an Informed Consent Form (ICF) indicating that they understand the purpose of the procedures required for the study and are willing to participate
2. When appropriate, pediatric participants, whose age, cognitive skills, reading abilities and maturity allow the understanding of the study protocol should provide written assent to participate.
3. Male or female participants between the ages of 3 months to 17 years at the time of signing the informed consent or providing assent
4. Have a confirmed diagnosis (genetic and/or histologic) of MVID
5. Are able to ingest reconstituted Crofelemer Powder for Oral Solution either orally (PO) or through a previously-placed G-tube or GJ-Tube (not via J-Tube)
6. Have, during the 8 weeks prior to baseline, a volume of PS that represents at least 50% (≥ 50%) of the participant's weekly hydration volume requirements
7. If female participants have reached menarche, the participant (and caregiver) agree that the participant will remain abstinent or use two accepted methods of birth control during the course of the treatment period and for an additional 30 days following the last dose of study drug.
8. Male participants (and caregiver) agree that the participant will remain abstinent or use contraception during the course of the treatment period and continue on for an additional 90 days following the last dose of study drug.

Exclusion Criteria

Within the last 4 weeks before study initiation, participants have:

1. had significant changes to PS requirements (i.e., ± > 20%)
2. had a new requirement for diuretics
3. had any infection requiring IV antibiotic administration
4. had a documented active gastrointestinal infection
5. initiated any new anti-diarrheal drug
6. had an increase in ALT, AST, or total bilirubin that is ≥2 times the participant's usual laboratory values
7. previously received an organ transplant
8. any currently-diagnosed malignancy
9. is pregnant or breastfeeding
10. any investigator determined criteria for inability to participate in this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Active Comparator: Dose Level 3/Treatment Period 1: 10mg/kg/dose 3x/day	Crofelemer Powder for Oral Solution	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)
Active Comparator: Dose Level 3/Treatment Period 2: 10mg/kg/dose 3x/day	Crofelemer Powder for Oral Solution	Participants will crossover to either crofelemer powder for oral solution or placebo comparator
Dose Level 1/Treatment Period 1: 1mg/kg/dose 3x/day	Crofelemer Powder for Oral Solution	Participants may be randomized to crofelemer powder for oral solution during Treatment Period 1 (1 month duration)
Dose Level 1/Treatment Period 1: Placebo 3x/day	Placebo Powder for Oral Solution	Participants may be randomized to the placebo comparator during Treatment Period 1 (1 month duration)
Dose Level 1/Treatment Period 2: 1mg/kg/dose 3x/day	Crofelemer Powder for Oral Solution	Participants will crossover to either crofelemer powder for oral solution or placebo comparator
Dose Level 2/Treatment Period 1: 3mg/kg/dose 3x/day	Crofelemer Powder for Oral Solution	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)
Dose Level 2/Treatment Period 1: Placebo 3x/day	Placebo Powder for Oral Solution	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)
Dose Level 2/Treatment Period 2: 3mg/kg/dose 3x/day	Crofelemer Powder for Oral Solution	Participants will crossover to either crofelemer powder for oral solution or placebo comparator
Dose Level 2/Treatment Period 2: Placebo 3x/day	Placebo Powder for Oral Solution	Participants will crossover to either crofelemer powder for oral solution or placebo comparator
Dose Level 3/Treatment Period 1: 10mg/kg/dose 3x/day	Crofelemer Powder for Oral Solution	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)
Dose Level 3/Treatment Period 1: Placebo 3x/day	Placebo Powder for Oral Solution	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)
Dose Level 3/Treatment Period 2: 10mg/kg/dose 3x/day	Crofelemer Powder for Oral Solution	Participants will crossover to either crofelemer powder for oral solution or placebo comparator
Dose Level 3/Treatment Period 2: Placebo 3x/day	Placebo Powder for Oral Solution	Participants will crossover to either crofelemer powder for oral solution or placebo comparator
Dose Level 1/Treatment Period 2: Placebo 3x/day	Placebo Powder for Oral Solution	Participants will crossover to either crofelemer powder for oral solution or placebo comparator
Active Comparator: Dose Level 1/Treatment Period 1: 1mg/kg/dose 3x/day	Crofelemer Powder for Oral Solution	Participants may be randomized to crofelemer powder for oral solution during Treatment Period 1 (1 month duration)
Placebo Comparator: Dose Level 1/Treatment Period 1: Placebo 3x/day	Placebo Powder for Oral Solution	Participants may be randomized to the placebo comparator during Treatment Period 1 (1 month duration)
Active Comparator: Dose Level 1/Treatment Period 2: 1mg/kg/dose 3x/day	Crofelemer Powder for Oral Solution	Participants will crossover to either crofelemer powder for oral solution or placebo comparator
Placebo Comparator: Dose Level 1/Treatment Period 2: Placebo 3x/day	Placebo Powder for Oral Solution	Participants will crossover to either crofelemer powder for oral solution or placebo comparator
Active Comparator: Dose Level 2/Treatment Period 1: 3mg/kg/dose 3x/day	Crofelemer Powder for Oral Solution	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)
Placebo Comparator: Dose Level 2/Treatment Period 1: Placebo 3x/day	Placebo Powder for Oral Solution	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)
Active Comparator: Dose Level 2/Treatment Period 2: 3mg/kg/dose 3x/day	Crofelemer Powder for Oral Solution	Participants will crossover to either crofelemer powder for oral solution or placebo comparator
Placebo Comparator: Dose Level 2/Treatment Period 2: Placebo 3x/day	Placebo Powder for Oral Solution	Participants will crossover to either crofelemer powder for oral solution or placebo comparator
Placebo Comparator: Dose Level 3/Treatment Period 1: Placebo 3x/day	Placebo Powder for Oral Solution	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)
Placebo Comparator: Dose Level 3/Treatment Period 2: Placebo 3x/day	Placebo Powder for Oral Solution	Participants will crossover to either crofelemer powder for oral solution or placebo comparator

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability	32 Weeks	Incidence of Adverse Events and Serious Adverse Events
Changes in Physical Examination	32 Weeks	Changes from baseline in physical exam and signs of dehydration, such as decreased urine output, sunken eyes, lethargy and abnormal skin turgor.
Changes in laboratory Values	32 Weeks	Incidence in changes from baseline of individual lab values within a chemistry, hematology and metabolic panel analysis.

Secondary Outcome Measures

Name	Time	Method
Average Daily Loose/Watery Stool Volume	Average Weekly for 32 weeks	Measure and record the volume of loose/watery stools each day using a toilet hat for stool collection
Average Daily Stool Frequency	Average Weekly for 32 weeks	Record the number of stools/day using the Daily Stool Diary
Average Daily Stool Consistency	Average Weekly for 32 weeks	Record stool consistency of each stool using the 7-point pediatric version of the Bristol Stool Form Scale in the Daily Stool Diary
Stool Electrolyte	Average Weekly for 32 weeks	Stool electrolyte (Na+, K+, Cl-) concentration measured in mEq/L
PS Volume Requirements	Average Weekly for 32 weeks	Record daily weekly TPN and IV fluid volume requirements in the Daily TPN and IV Fluid Diary
Average Weekly Supplemental Electrolytes	Average Weekly for 32 Weeks	Record daily any IV supplements of Na+, K+, Cl-, or acetate on the Daily PS Diary

Trial Locations

Locations (3)

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

UOS Gastroenterolgia e Riabilitazione nutrizionale Piazza Sant' Onofrio 4; 🇮🇹 Rome, Italy

Al Jalila Children's Hospital; 🇦🇪 Dubai, United Arab Emirates