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

The study consists of an initial randomized double-blind placebo-controlled study, followed by an up to 48-week partially blinded extension phase.

The double-blind study phase is a randomized, double-blind, placebo-controlled, dose-escalating study with a placebo crossover 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, across treatment periods within each dose level and through the end of the double-blind treatment period will be descriptively summarized. For secondary objectives, changes from the Baseline Period will be assessed.

After completion of the study and the No Treatment Period, if the Investigator and the DMC consider it appropriate for the participant's best interest based on safety and tolerability, the participant will be eligible to enter a Partially Blinded Extension Phase. Following approval by the DMC, the participant will enter the extension phase for up to 48 additional weeks of treatment with crofelemer at the dose selected by the DMC. The Investigator and the Sponsor will remain blinded to the selected dose.

Inclusion criteria

• 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
• 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.
• Male or female participants from birth to < 18 years at the time of signing the informed consent or providing assent
• Have a confirmed diagnosis (genetic and/or histologic) of MVID
• 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)
• Have, during the 8 weeks prior to baseline, an average weekly volume of PS that represents at least 50% (≥ 50%) of the participant's weekly hydration volume requirements
• 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.
• 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:

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