Evaluation of Safety, Tolerability and Efficacy of Crofelemer Following Multiple Ascending Doses of Crofelemer Powder for Oral Solution in Pediatric Participants With Microvillus Inclusion Disease (MVID)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 6
- 试验地点
- 6
- 主要终点
- Safety and Tolerability
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The double-blind phase is a randomized, double-blind, placebo-controlled, dose-escalating study with a placebo cross-over design within each participant at each dose level in this ultra-rare MVID participant population. During the partially blinded extension phase, participants will receive crofelemer at a dose selected by the DMC, with the Investigator and the Sponsor remaining blinded to the selected dose.
入排标准
- 年龄范围
- 3 Months 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Dose Level 2/Treatment Period 1: 3mg/kg/dose 3x/day
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)
干预措施: Crofelemer Powder for Oral Solution (Drug)
Dose Level 1/Treatment Period 1: 1mg/kg/dose 3x/day
Participants may be randomized to crofelemer powder for oral solution during Treatment Period 1 (1 month duration)
干预措施: Crofelemer Powder for Oral Solution (Drug)
Dose Level 1/Treatment Period 2: 1mg/kg/dose 3x/day
Participants will crossover to either crofelemer powder for oral solution or placebo comparator
干预措施: Crofelemer Powder for Oral Solution (Drug)
Dose Level 1/Treatment Period 1: Placebo 3x/day
Participants may be randomized to the placebo comparator during Treatment Period 1 (1 month duration)
干预措施: Placebo Powder for Oral Solution (Drug)
Dose Level 2/Treatment Period 2: 3mg/kg/dose 3x/day
Participants will crossover to either crofelemer powder for oral solution or placebo comparator
干预措施: Crofelemer Powder for Oral Solution (Drug)
Dose Level 3/Treatment Period 1: 10mg/kg/dose 3x/day
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)
干预措施: Crofelemer Powder for Oral Solution (Drug)
Dose Level 3/Treatment Period 2: 10mg/kg/dose 3x/day
Participants will crossover to either crofelemer powder for oral solution or placebo comparator
干预措施: Crofelemer Powder for Oral Solution (Drug)
Dose Level 2/Treatment Period 1: Placebo 3x/day
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)
干预措施: Placebo Powder for Oral Solution (Drug)
Dose Level 2/Treatment Period 2: Placebo 3x/day
Participants will crossover to either crofelemer powder for oral solution or placebo comparator
干预措施: Placebo Powder for Oral Solution (Drug)
Dose Level 3/Treatment Period 1: Placebo 3x/day
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)
干预措施: Placebo Powder for Oral Solution (Drug)
Dose Level 3/Treatment Period 2: Placebo 3x/day
Participants will crossover to either crofelemer powder for oral solution or placebo comparator
干预措施: Placebo Powder for Oral Solution (Drug)
Dose Level 1/Treatment Period 2: Placebo 3x/day
Participants will crossover to either crofelemer powder for oral solution or placebo comparator
干预措施: Placebo Powder for Oral Solution (Drug)
结局指标
主要结局
Safety and Tolerability
时间窗: 32 Weeks
Incidence of Adverse Events and Serious Adverse Events
Changes in Physical Examination
时间窗: 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
时间窗: 32 Weeks
Incidence in changes from baseline of individual lab values within a chemistry, hematology and metabolic panel analysis.
次要结局
- Average Daily Loose/Watery Stool Volume(Average Weekly for 32 weeks)
- Average Daily Stool Frequency(Average Weekly for 32 weeks)
- Average Daily Stool Consistency(Average Weekly for 32 weeks)
- Stool Electrolyte(Average Weekly for 32 weeks)
- PS Volume Requirements(Average Weekly for 32 weeks)
- Average Weekly Supplemental Electrolytes(Average Weekly for 32 Weeks)