A 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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
6
Crofelemer Powder for Oral Solution
Matching Placebo Powder for Oral Solution
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
Safety and Tolerability
Incidence of Adverse Events and Serious Adverse Events
Time frame: 32 Weeks
Changes in Physical Examination
Changes from baseline in physical exam and signs of dehydration, such as decreased urine output, sunken eyes, lethargy and abnormal skin turgor.
Time frame: 32 Weeks
Changes in Laboratory Values
Incidence in changes from baseline of individual lab values within a chemistry, hematology and metabolic panel analysis.
Time frame: 32 Weeks
Average PS Volume Requirements Normalized to Body Weight
Record daily weekly TPN and IV fluid volume requirements in the Daily TPN and IV Fluid Diary, and divide the value per body weight for the corresponding study visit (mL/kg)
Time frame: Average Weekly for 32 weeks
Average Loose/Watery Stool Volume
Measure and record the volume of loose/watery stools using a toilet hat for stool collection during 24 hours before each study visit
Time frame: Average every 2 weeks for 32 weeks
Average TPN (including lipids) Volume Requirements
Record daily weekly TPN volume requirements in the Daily TPN and IV Fluid Diary
Time frame: Average weekly for 32 weeks
Average Supplemental IV Fluids Volume Requirements
Record daily weekly supplemental IV fluid volume requirements in the Daily TPN and IV Fluid Diary
Time frame: Average weekly for 32 weeks
Average Supplemental Electrolytes
Record daily any supplements of Na+, K+, Cl- in PS and, separately in TPN and in IV fluids, in the Daily PS Diary
Time frame: Average weekly for 32 weeks
Average Acetate or Lactate Supplementation
Record daily any supplements of acetate or lactate in PS and, separately in TPN and in IV fluids, in the Daily PS Diary
Time frame: Average weekly for 32 weeks
Stool Electrolytes
Stool electrolytes (Na+, K+, Cl-) concentration measured in mEq/L
Time frame: Measurement at baseline, week 20 and week 24
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