A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm Study to Evaluate the Efficacy and Safety of RZ358 in Patients With Congenital Hyperinsulinism
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Rezolute
- 入组人数
- 56
- 试验地点
- 18
- 主要终点
- Glycemic efficacy: Target glucose control
研究概览
简要总结
The Phase 3 pivotal study is designed to evaluate the efficacy and safety of RZ358 for the treatment of congenital hyperinsulinism (HI) as add-on to standard-of-care (SOC) therapy compared to SOC alone over 24 weeks and to evaluate the longer-term safety and efficacy of RZ358 during a subsequent open-label extension (OLE) period.
详细描述
Congenital hyperinsulinism (HI) is the most common cause of recurrent hypoglycemia in neonates and infants with an incidence of approximately 1 in 25,000 to 1 in 50,000 live births in the general population, and as high as 1 in 2,500 in certain populations with substantial consanguinity. Despite improved recognition, there is no satisfactory treatment or cure for congenital HI. Current medical therapies for congenital HI are directed at reducing or eliminating insulin production and/or secretion from the beta-cell. These current medications, however, achieve suboptimal glycemic control and/or have undesirable side effects. A therapy which safely and effectively attenuates the activity of insulin would address an important unmet need for these and other conditions associated with HI. This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled (SOC alone), parallel-arm, efficacy, and safety study of RZ358 in participants with congenital HI who have not achieved adequate hypoglycemia control with reasonable attempts at using usual SOC medical therapy. The study will randomize approximately 48 participants (≥1 year to ≤45 years of age) in a 1:1 ratio into 2 dosing arms (5 or 10 mg/kg with) and further randomize participants within each dosing level in a 2:1 ratio to receive RZ358 as add-on to SOC or placebo as add-on to SOC. An additional open-label (OL) arm will be conducted in parallel for participants who are ≥3 months to <1 year old (n=8), Upon completion of the pivotal treatment period (24-weeks), participants may roll-over to the OLE period at the discretion of the investigator and Sponsor.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double blind
入排标准
- 年龄范围
- 3 Months 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At screening, aged ≥ 3 months and ≤ 45 years old.
- •An established clinical diagnosis of congenital HI (hyperinsulinism), with or without identification of a known monogenic variant by genetic testing.
- •Participant has failed to achieve adequate glycemic control with appropriate and reasonable trials of locally accepted and available Standard of Care (SOC) medical therapies (e.g., diazoxide and somatostatin analogs (SSAs)) per the judgment of the investigator.
- •Experiencing ≥ 3 hypoglycemia events per week by screening Self-Monitoring Blood Glucose (SMBG) and average daily percent time with hypoglycemia of ≥ 8% of the monitored screening Continuous Glucose Monitor (CGM) time.
排除标准
- •Alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), total bilirubin (TB), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) ≥ 1.5 × the upper limit of normal for the age-specific reference range, regardless of assessed significance.
- •Body mass index (BMI) ≥ 35 kg/m2 for participants aged 18 years and above, or BMI ≥ 99% (percentile) per Centers for Disease Control and Prevention growth charts for participants > 12 and < 18 years of age (no BMI exclusion for participants ≤ 12 years of age).
- •A known clinical diagnosis of diabetes or pre-diabetes, or a history of insulin dependency within 3 months of screening.
- •Average daily percent time with hyperglycemia ≥ 5% of the monitored screening continuous glucose monitoring (CGM) time.
- •Known allergy or sensitivity to RZ358 or any component of the drug.
研究组 & 干预措施
SoC (Standard-of-Care) + RZ358 (5 mg/kg) or Placebo
Participants ≥1 year old who receive SOC therapy and 5 mg/kg of RZ358 or placebo
干预措施: RZ358 (5 mg/kg) + SOC (Standard-of-Care) or Placebo + SOC (Drug)
SoC + RZ358 (10 mg/kg) or Placebo
Participants ≥1 year old who receive SOC therapy and 10 mg/kg of RZ358 or placebo
干预措施: RZ358 (10 mg/kg) or Placebo + SOC (Drug)
Open Label Arm, SoC + RZ358 (start 5mg/kg and increase to 10 mg/kg per protocol schedule
Infant participants from ≥3 months to <1 year old who receive SOC therapy + RZ358 starting at 5 mg/kg and increasing to 10 mg/kg of RZ358, as needed, per the protocol schedule
干预措施: RZ358 (5-10 mg/kg) + SOC (Drug)
结局指标
主要结局
Glycemic efficacy: Target glucose control
时间窗: 24 weeks
Change in average weekly hypoglycemia events from baseline by point-of-care Self-Monitoring Blood Glucose (SMBG)
次要结局
- Glycemic efficacy: Occurrence of hypoglycemia(24 weeks)
- Safety Assessments: safety and tolerability of RZ358 in patients with congenital hyperinsulinism, Laboratory tests evaluated for significant changes from baseline by treated groups(Time Frame: 24 weeks, plus up to two years of Open-Label Extension (OLE) period)
- Other Glycemic efficacy: Self-Monitoring Blood Glucose (SMBG) Weekly Assessment(24 weeks)
- Other Glycemic efficacy: Continuous Glucose Monitor (CGM) Daily Assessment(24 weeks)
- Safety Assessments: safety and tolerability of RZ358 in patients with congenital hyperinsulinism(24 weeks, plus up to two years of Open-Label Extension (OLE) period)
- Other Glycemic efficacy: Continuous Glucose Monitor (CGM) Overnight Assessment(24 weeks)
- Other Glycemic efficacy: Self-Monitoring Blood Glucose (SMBG)(24 weeks)