An Open-Label Multiple-Dose Study of RZ358 in Patients With Congenital Hyperinsulinism
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Rezolute
- 入组人数
- 23
- 试验地点
- 17
- 主要终点
- Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)
研究概览
简要总结
The objective of this trial is to evaluate the safety, tolerability and glucose-raising effects of RZ358 in patients with Congenital Hyperinsulinism (HI).
详细描述
There is a significant unmet medical need to develop new therapies aimed at preventing chronic recurrent hypoglycemia in congenital HI, the most common cause of persistent hypoglycemia in children. RZ358 is a human mAb that allosterically attenuates excessive insulin action on target cells. Therefore, RZ358 is ideally suited as a potential therapy for hyperinsulinism, and it is being developed to treat the hypoglycemia associated with diseases such as congenital HI. This is a Phase 2, multicenter, open label clinical study designed to assess the safety and efficacy of four progressively higher doses of RZ358 in separate groups of patients with hyperinsulinemic hypoglycemia due to Congenital HI, not adequately controlled with or without current standard of care. A screening period of up to 5 weeks will evaluate eligibility. Once enrolled, RZ358 will be administered bi-weekly over 8 weeks, and then patients will complete a post-treatment follow-up period of 13 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female age 2-45 years old (except age 12-45 in US) with an established clinical diagnosis of congenital hyperinsulinism
- •Able to provide written informed consent or, as applicable, assent
- •Confirmed hypoglycemia as assessed by CGM, SMBG, and clinical evaluation, during Screening
- •Willingness to use contraception if of child-bearing potential
排除标准
- •Out of range blood work for study entry
- •Body Mass index outside of study entry criteria
- •History of malignancy
- •Clinically significant diseases, seropositivity for HIV, hepatitis B or C antibody
- •Use of systemic corticosteroids within 30 days before Screening
- •Known or suspected allergy to the study drug
- •Recent use of an investigational drug or treatment, or participation in an investigational study
- •Pregnant or lactating women
- •History of drug abuse or excessive alcohol use
研究组 & 干预措施
RZ358 Cohort 1
干预措施: RZ358 Sequential Group Cohort 1 (Drug)
RZ358 Cohort 2
干预措施: RZ358 Sequential Group Cohort 2 (Drug)
RZ358 Cohort 3
干预措施: RZ358 Sequential Group Cohort 3 (Drug)
RZ358 Cohort 4
干预措施: RZ358 Sequential Group Cohort 4 (Drug)
结局指标
主要结局
Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)
时间窗: 8 weeks
The median of average daily percent time within the glucose target range 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline and End of Treatment (EOT) is reported.
Median Percent Change of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM From Baseline (BL)
时间窗: 8 weeks
The average daily percent time within the glucose target range (70-180 mg/dL) is compared from baseline to end of treatment (EOT) and the median percent change of that difference is reported.
Repeat Dose Pharmacokinetics of RZ358
时间窗: Pre dose Weeks 1,3,5,7, 1-hr post dose Week 1 and Week 7, and Follow up on Days 14, Day 28, Day 42, and Day 105
All patients who received RZ358 and for whom the primary PK data was considered to be sufficient and interpretable were to be included in the PK analyses. Individual and mean plasma concentration data is summarized descriptively at the specified timepoints. The results of this study may be combined with those of other studies for analysis and modeling (e.g., population PK and PK-PD), and therefore the PK parameters are reported separately, as part of an iterative population PK approach.
次要结局
- Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)(8 weeks)
- Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)(8 weeks)
- Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)(8 weeks)
- Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)(8 weeks)
- Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)(8 weeks)
- Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)(8 weeks)
- Occurrence of Hypoglycemia During Fasting Challenge(8 Weeks)
- Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)(8 weeks)
- Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)(8 weeks)
- Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)(8 weeks)
- Median Percent Change of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM From Baseline (BL)(8 weeks)