ascending doses of crofelemer powder for oral solution in pediatric microvillus inclusion disease (mvid)

Conditions: Microvillus Inclusion Disease; Congenital Disorders; Rare Diseases

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

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.

Eligibility criteria:
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