A Phase 2a, Randomized, Double-Blind, Placebo Controlled, Dose Ranging, Multicenter Study to Determine the Safety, Tolerance, and Efficacy of Larazotide Acetate (AT-1001) in Celiac Disease Subjects During Gluten Challenge.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- To demonstrate the safety and tolerability of multiple, oral doses of larazotide acetate in celiac disease subjects that maintain a gluten-free diet.
研究概览
简要总结
This study was run to determine the safety, tolerance, and efficacy of multiple doses of larazotide acetate in subjects with celiac disease following a gluten challenge.
详细描述
CLIN1001-004 was a randomized, double-blind, placebo controlled, dose-ranging, 7-arm, multicenter study with a gluten challenge. The objects were multiple dose safety and tolerance; efficacy (intestinal permeability [change in urinary LAMA ratio] and disease signs and symptoms) following gluten challenge.
Following a 21-day screening period, subjects were randomized to one of seven treatments groups: four groups received larazotide acetate (0.25 mg, 1 mg, 4 mg or 8 mg TID) along with an 800 mg gluten challenge, one group received placebo with an 800 mg gluten challenge, a safety control arm received the highest dose of larazotide acetate (8 mg TID) and gluten placebo and the last group received drug placebo and gluten placebo. The gluten challenge was administered as capsules (800 mg TID) with each main meal for a total of 2.4 g daily. Drug or drug placebo was administered TID 15 minutes prior to each main meal. Subjects received their assigned treatments for two weeks (Day 0 through Day 14) and came to clinic for a follow-up visit one week later (Day 21). Subjects remained on their gluten-free diet for the duration of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
double-blind
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have been diagnosed with celiac disease by biopsy for ≥ 6 months.
- •Have a Anti-Tissue Transglutaminase (tTG) ≤ 10 EU as measured by serology.
- •Must be on a gluten-free diet for at least the past 6 months.
排除标准
- •Have any chronic active GI disease other than celiac disease (e.g., IBS, Crohn's, Colitis).
- •Have diabetes (Type 1 or Type 2).
- •Chronically consumes non-steroidal anti-inflammatory agents ("NSAIDs") or takes proton-pump inhibitors.
- •Consuming oral corticosteroids or immune suppressants.
研究组 & 干预措施
Placebo + Gluten
placebo TID + gluten 800 mg TID administered orally in capsules
干预措施: Placebo (Drug)
Placebo + Gluten placebo
placebo TID + gluten placebo TID administered orally in capsules
干预措施: Placebo (Drug)
Larazotide acetate 8 mg + Gluten placebo
Safety Control Arm. Larazotide acetate 8 mg TID + gluten placebo TID administered orally in capsules
干预措施: larazotide acetate (Drug)
Larazotide acetate 0.25 mg + Gluten
Larazotide acetate 0.25 mg TID + gluten 800 mg TID administered orally in capsules
干预措施: larazotide acetate (Drug)
Larazotide acetate 1 mg + Gluten
Larazotide acetate 1 mg TID + gluten 800 mg TID administered orally in capsules
干预措施: larazotide acetate (Drug)
Larazotide acetate 4 mg + Gluten
Larazotide acetate 4 mg TID + gluten 800 mg TID administered orally in capsules
干预措施: larazotide acetate (Drug)
Larazotide acetate 8 mg + Gluten
Larazotide acetate 8 mg TID + gluten 800 mg TID administered orally in capsules
干预措施: larazotide acetate (Drug)
结局指标
主要结局
To demonstrate the safety and tolerability of multiple, oral doses of larazotide acetate in celiac disease subjects that maintain a gluten-free diet.
时间窗: Safety measurements were performed at Screening and at Day 0, 7, 14, and 21 ('End of Study'). Any change from baseline value was calculated at each subsequent visit until "End of Study" (Day 21).
Safety endpoints assessed in this study were adverse events, vital signs, hematology, clinical chemistry, urinalysis and ECG
To evaluate the efficacy of multiple dose levels of larazotide acetate in preventing intestinal permeability changes induced by gluten challenge
时间窗: On Days 0, 6, 13, and 20 subjects drank a solution of lactulose and mannitol. Subject's urine was collected during the day on Day 0 and overnight prior to subsequent visits and analyzed for LAMA recoveries via standardized methodologies.
The primary efficacy outcome was the Day 0-to-Day 14 change in urinary LAMA ratio ( a measure of intestinal permeability) as a response to gluten
次要结局
- Changes in daily and weekly reported health outcomes(Symptom diary - daily; PGWBI - weekly; GSRS - weekly)
- Changes in urinary mannitol fractional excretion between Day 0 to Day 7 to Day 14(See Primary Outcome Measure No. 2)
- Changes in urinary LAMA ratios between Day 0 to Day 7(See Primary Outcome Measure No. 2)
- Changes in urinary lactulose fractional excretion between Day 0 to Day 7 to Day 14(See Primary Outcome Measure No. 2)
- Change in anti-tTG levels from Screening to Day 21(Screening and Day 21)
- Change in urinary nitrite / nitrate levels from Day 0 to Day 14(Day 0 and Day 14)
- Change in cell markers and cytokines from PBMCs(Days 0, 7, 14 and 21)
- Changes in zonulin level(Days 0, 7, 14 and 21)