A Randomized Trial in 2 Parts: Double-Blind, Placebo-Controlled, Crossover Part 1 and Open-label Part 2, Evaluating the Efficacy and Safety of Dasiglucagon for the Treatment of Children With Congenital Hyperinsulinism
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 6
- 主要终点
- Mean Intravenous Glucose Infusion Rate
研究概览
简要总结
The objective of the trial is to evaluate the efficacy of dasiglucagon in reducing glucose requirements in children with persistent congenital hyperinsulinism (CHI) requiring continuous intravenous (IV) glucose administration to prevent/manage hypoglycemia.
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)
入排标准
- 年龄范围
- 7 Days 至 364 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CHI diagnosis established based on the following:
- •Hyperinsulinemia: plasma insulin above the limit of detection of the assay documented during an event of hypoglycemia, and/or
- •Hypofattyacidemia: plasma free fatty acid <1.7 mmol/L, and/or
- •Hypoketonemia: Beta-hydroxybutyrate <1.8 mmol/L, and/or
- •Glycemic response: an increase in plasma glucose (PG) of >30 mg/dL (1.7 mmol/L) after 1 mg IV or intramuscular (IM) glucagon administration
- •Male or female, age ≥7 days and <12 months at screening
- •Body weight of ≥2.0 kg (4.4 lbs.)
- •Continuous IV glucose requirement to prevent hypoglycemia
排除标准
- •Is suspected of having a transient form of CHI (e.g., transient hyperinsulinism due to maternal diabetes or perinatal stress)
- •Was born preterm below 34 weeks of gestational age
- •Presence of hypertension or hypotension, including circulatory instability requiring supportive medication or presence of pheochromocytoma
- •Known or suspected presence of severe brain damage
- •Evidence of metabolic, endocrine, or syndromic causes of hypoglycemia not due to hyperinsulinism
- •Use of systemic corticosteroids, e.g., hydrocortisone >20 mg/m^2 body surface area or equivalent within 5 days before screening
- •Prior use of lanreotide, sirolimus (mechanistic target of rapamycin [mTOR] inhibitors), anti-inflammatory biological agents, or other immune modulating agents. Prior use of octreotide is allowed after a minimum of 48 hour washout before randomization.
- •Any clinically significant abnormality identified on echocardiogram that in the opinion of the investigator would affect the subject's ability to participate in the trial
- •Any recognized clotting or bleeding disorder
- •The use of prescription or non-prescription medications known to cause QT prolongation
研究组 & 干预措施
dasiglucagon first then placebo
48 hours of dasiglucagon subcutaneous (sc) infusion starting at 10 µg/hour with crossover to 48 hours placebo sc infusion (part 1) followed by 21 days of dasiglucagon sc infusion (part 2).
干预措施: dasiglucagon (Drug)
dasiglucagon first then placebo
48 hours of dasiglucagon subcutaneous (sc) infusion starting at 10 µg/hour with crossover to 48 hours placebo sc infusion (part 1) followed by 21 days of dasiglucagon sc infusion (part 2).
干预措施: Placebo (Drug)
placebo first then dasiglucagon
48 hours of placebo sc infusion with crossover to 48 hours dasiglucagon sc infusion starting at 10 µg/hour (part 1) followed by 21 days of dasiglucagon sc infusion (part 2).
干预措施: dasiglucagon (Drug)
placebo first then dasiglucagon
48 hours of placebo sc infusion with crossover to 48 hours dasiglucagon sc infusion starting at 10 µg/hour (part 1) followed by 21 days of dasiglucagon sc infusion (part 2).
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Intravenous Glucose Infusion Rate
时间窗: Hours 36-48 after initiation of trial drug (Part 1)
Mean intravenous (IV) glucose infusion rate (GIR) in the last 12 hours of each treatment period during Part 1, the crossover part of the trial (dasiglucagon or placebo administration).
次要结局
- Carbohydrates Administered(Days 5 to 25)
- Mean Intravenous Glucose Infusion Rate(48 hours after initiation of trial drug (Part 1))
- Mean Intravenous Glucose Infusion Rate Below 10 mg/kg/Minute(Hours 36-48 after initiation of trial drug (Part 1))
- Time to Complete Weaning Off Intravenous Glucose(Days 5 to 25 (Part 2))
- Hypoglycemia Event Rate in Part 2(Days 5 to 25)
- Clinically Significant Hypoglycemia Events in Part 2(Days 5 to 25)
- Time to Actual Hospital Discharge(Days 5 to 25)
- Time to Pancreatic Surgery(Days 5 to 25)
- Carbohydrates Administered Intravenously(Days 5 to 25)
- Carbohydrates Administered Parenterally(Days 5 to 25)
- Carbohydrates Administered Orally(Days 5 to 25)
- Carbohydrates Administered Via Gastric Feed(Days 5 to 25)
- Time in Range in Part 2(Days 5 to 25)
- Time in Hypoglycemia in Part 2(Days 5 to 25)
- Time in Clinically Significant Hypoglycemia in Part 2(Days 5 to 25)
- Hypoglycemia Episodes in Part 2(Days 5 to 25)
- Clinically Significant Hypoglycemia Episodes in Part 2(Days 5 to 25)
- Extent of Hypoglycemia in Part 2(Days 5 to 25)
- Extent of Clinically Significant Hypoglycemia in Part 2(Days 5 to 25)
- Time in Hyperglycemia in Part 2(Days 5 to 25)