Determination of the rhIGF-1/rhIGFBP-3 Dose, Administered as a Continuous Infusion, Required to Establish and Maintain Longitudinal Serum IGF-1 Levels Within Physiological Levels in Premature Infants, to Prevent Retinopathy of Prematurity A Phase 2, Randomized Controlled, Assessor-blind, Dose Confirming, Pharmacokinetic, Safety and Efficacy, Multicenter Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 121
- 试验地点
- 24
- 主要终点
- Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population
研究概览
简要总结
To compare the severity of retinopathy of prematurity (ROP) among treated infants with an untreated control population, matched for gestational age at birth while confirming the dose of rhIGF-1/rhIGFBP-3 is safe and efficacious.
详细描述
When preterm infants are deprived of their natural intrauterine environment they lose access to important factors, normally found in utero, such as proteins, growth factors, and cytokines. It has been demonstrated that insulin-like growth factor-1 (IGF-1) is one such factor. In utero these biological factors are introduced to the fetus via placental absorption or ingestion from amniotic fluid. Deprivation of such factors is likely to cause inhibition or improper stimulation of important pathways, which in the case of the eye may cause abnormal retinal vascular growth, the hallmark of retinopathy of prematurity (ROP).
Retinopathy of prematurity is the major cause of blindness in children in the developed and developing world, despite the availability of current treatment of late-stage ROP. As developing countries provide more neonatal and maternal intensive care, which increases the survival of preterm born infants, the incidence of ROP is increasing.
This phase 2 study was originally designed in 3 sections, Sections A, B, and C which are now complete. The protocol was amended and patients enrolled from this point forward will be enrolled into Section D.
In Study Section D, a total of 120 subjects (GA of 23 weeks + 0 days to 27 weeks + 6 days) will be randomly assigned with 1:1 allocation ratio to either treatment with rhIGF-1/rhIGFBP-3 or to receive standard neonatal care (Control Group) to obtain at least 80 evaluable subjects. Duration of infusion will last at longest from Study Day 0 (day of birth) up to and including PMA 29 weeks + 6 days, when the subject's endogenous production of IGF-1 is considered sufficient to maintain physiologic serum IGF-1 levels. After discontinuation of study drug infusion, each subject will be followed to PMA 40 weeks ± 4 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- — 至 1 Day（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent from parents/guardians;
- •Subject must be between GA of 26 weeks + 0 days and 27 weeks + 6 days (Study Section A) or between GA of 23 weeks + 0 days and 27 weeks + 6 days (Study Sections B, C, and D), inclusive
排除标准
- •Subjects born small for gestational age (SGA), ie, body weight at birth <-2 standard deviation score (SDS) (Study Section A only)
- •Detectable gross malformation
- •Known or suspected chromosomal abnormality, genetic disorder, or syndrome, according to the Investigator's opinion
- •Persistent blood glucose level <2.5 mmol/L or >10 mmol/L at Study Day 0 (day of birth) to exclude severe congenital abnormalities of glucose metabolism
- •Anticipated need of administration of erythropoietin (rhEPO) during treatment with study drug.
- •Any maternal diabetes requiring insulin during the pregnancy
- •Clinically significant neurological disease according to the Investigator's opinion(Stage 1 IVH allowed)
- •Any other condition or therapy that, in the Investigator's opinion, may pose a risk to the subject or interfere with the subject's ability to be compliant with this protocol or interfere with interpretation of results
- •Monozygotic twins
- •Subject participating or plans to participate in a clinical study of another investigational study drug
研究组 & 干预措施
rhIGF-I/rhIGFBP-3
Continuous IV Infusion
干预措施: rhIGF-I/rhIGFBP-3 (Drug)
结局指标
主要结局
Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population
时间窗: End of study
ROP was measured by central exams with fundus photography. Maximum severity of ROP stage across all retinal examinations included International Classification of Retinopathy of Prematurity, a 5 stage system, for the classification of ROP with 7 different outcomes of the ROP stage in each retinal examination: 0, 1, 2, 3, 3+, 4, and 5. This is an ordinal scale with higher numbers indicating a more severe outcome. The maximum severity of ROP across all time points was assessed from 31 PMA weeks up to 40 PMA Weeks +/- 4 days (end of study).
次要结局
- Time to Discharge From Neonatal Intensive Care (TDNIC)(Day 0 to 40 Weeks Post Menstrual Age (EOS))
- Rate of Change in Body Weight(Day 0 to 40 Weeks Post Menstrual Age (EOS))
- Number of Participants With Bronchopulmonary Dysplasia (BPD)(At 36 Weeks Post Menstrual Age)
- Rate of Change in Length(Day 0 to 40 Weeks Post Menstrual Age (EOS))
- Brain Development Assessed by Brain Volume at 40 Weeks PMA/EOS(40 Weeks PMA/ (EOS) +/- 4 days)
- Percentage of Participants With Maximum Severity of ROP Stage Greater Than or Equal to 3 at Any Time During the Study(Day 0 to 40 Weeks Post Menstrual Age (EOS))
- Rate of Change in Head Circumference(Day 0 to 40 Weeks Post Menstrual Age (EOS))
- Area Under Curve for Maximum Severity of ROP Stage (AUC for ROP)(Every 1-2 weeks starting at 31 weeks PMA/ EOS +/- 4 days)
- Serum Concentrations of Acid Labile Sub-unit (ALS) After Intravenous (IV) Infusion of rhIGF-1/rhIGFBP-3(Day 7 and Week 40 Post Menstrual Age)
- Percentage of Participants With Intraventricular Hemorrhage (IVH)(Day 0 to 40 Weeks Post Menstrual Age (EOS))
- Percentage of Serum IGF-1 Concentrations Falling Within Target Range After Infusion of rhIGF-1/rhIGFBP-3(Day 0 to 40 Weeks Post Menstrual Age (EOS))
- Serum Concentrations of IGFBP-3 After Intravenous (IV) Infusion of rhIGF-1/rhIGFBP-3(Day 0 and Week 40 Post Menstrual Age)
- Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE)(Day 0 to 40 Weeks Post Menstrual Age (EOS))