Retinopathy of Prematurity (ROP)
Conditions
Keywords
insulin-like growth factor, ROP, IGF-I, BPD, bronchopulmonary dysplasia, retinopathy of prematurity
Brief summary
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.
Detailed description
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.
Interventions
Continuous intravenous infusion
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 1 Days
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Bronchopulmonary Dysplasia (BPD) | At 36 Weeks Post Menstrual Age | Severity of BPD as mild, moderate and severe were based on the National Institute of Child Health and Human Development (NICHD) guidelines for preterm infants born at gestational age (GA) less than (\<) 32 weeks. Mild: oxygen requirement during the first 28 days but in room air at PMA 36 weeks or discharge to home, whichever comes first. Moderate BPD: oxygen requirement during the first 28 days and oxygen \<30 percent (%) at PMA 36 weeks or discharge to home, whichever comes first. Severe BPD: oxygen requirement during the first 28 days and oxygen greater than equal (≥)30% through head hood or nasal canula, or continuous positive airway pressure, or mechanical ventilation, or high flow nasal cannula ≥2 L/min at PMA 36 weeks or discharge to home, whichever comes first. |
| Rate of Change in Body Weight | Day 0 to 40 Weeks Post Menstrual Age (EOS) | The rate of change is the rate of specific body weight change per day in kilogram (kg). |
| Rate of Change in Length | Day 0 to 40 Weeks Post Menstrual Age (EOS) | The rate of change is the length change per day in centimeter (cm). |
| Rate of Change in Head Circumference | Day 0 to 40 Weeks Post Menstrual Age (EOS) | The rate of change is the head circumference change per day in centimetre (cm). |
| Brain Development Assessed by Brain Volume at 40 Weeks PMA/EOS | 40 Weeks PMA/ (EOS) +/- 4 days | Brain volume was measured using cerebral magnetic resonance imaging (MRI). Brain volume included cerebrospinal volume, gray matter volume, white matter volume, and total cerebellar volume |
| Percentage of Participants With Intraventricular Hemorrhage (IVH) | Day 0 to 40 Weeks Post Menstrual Age (EOS) | Development of intraventricular hemorrhage was assessed by cerebral ultrasound and coded as a binary endpoint (presence or absence of IVH). |
| Time to Discharge From Neonatal Intensive Care (TDNIC) | Day 0 to 40 Weeks Post Menstrual Age (EOS) | — |
| 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) | 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. |
| 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) | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse event was defined as the onset of any AE or if the severity of a pre-existing AE worsened any time on or after the date of first dose of investigational product. |
| 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 samples were collected from treated and control participants for quantification of IGF-1 using validated immunoassays. Target range of serum IGF-1 was 28-109 mcg/L. The percentage of serum IGF-1 levels across treated participants that fall within the range was reported. |
| Serum Concentrations of IGFBP-3 After Intravenous (IV) Infusion of rhIGF-1/rhIGFBP-3 | Day 0 and Week 40 Post Menstrual Age | — |
| 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 | — |
| Area Under Curve for Maximum Severity of ROP Stage (AUC for ROP) | Every 1-2 weeks starting at 31 weeks PMA/ EOS +/- 4 days | Integration of the maximum severity of ROP stage and the duration of the time interval with respect to each retinal examination. AUC for the maximum severity of ROP was calculated using the trapezoidal rule. The area between each 2 visits was calculated by multiplying the average of the maximum severities of the 2 visits by the difference in days and analyzed using the van Elteren test. ROP is classified according to the International Classification and is subdivided into 5 stages (1-5) with higher values representing greater severity. |
Countries
Italy, Netherlands, Poland, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted in multiple centres in Italy, the Netherlands, Poland, Sweden, the United Kingdom and the United States between 18 Jun 2010 and 30 March 2016.
Pre-assignment details
A total of 121 participants were enrolled and randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| rhIGF-1/rhIGFBP-3 Participants received rhIGF-I/rhIGFBP-3 250 mcg/kg for 24 hours through continuous IV infusion from Day 0 up to 29 weeks 6 days of PMA. | 61 |
| Standard of Care (Control) Participants in this control group do not received any treatment other than the standard care. | 60 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Decision | 0 | 1 |
| Overall Study | Adverse Event | 11 | 9 |
| Overall Study | Other Unspecified | 0 | 1 |
| Overall Study | Protocol Deviation | 2 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | rhIGF-1/rhIGFBP-3 | Standard of Care (Control) | Total |
|---|---|---|---|
| Age, Continuous | 25.60 Weeks STANDARD_DEVIATION 1.207 | 25.62 Weeks STANDARD_DEVIATION 1.397 | 25.61 Weeks STANDARD_DEVIATION 1.3 |
| Sex: Female, Male Female | 22 Participants | 21 Participants | 43 Participants |
| Sex: Female, Male Male | 39 Participants | 39 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 58 / 61 | 60 / 60 |
| serious Total, serious adverse events | 48 / 61 | 37 / 60 |
Outcome results
Primary
Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population
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).
Time frame: End of study
Population: Full Analysis Set (FAS) included all randomized participants who received the study drug and participants in the control group who received Standard of Care.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rhIGF-1/rhIGFBP-3 | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | ROP of Stage 5 | 0 participants |
| rhIGF-1/rhIGFBP-3 | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | ROP of Stage 3 | 6 participants |
| rhIGF-1/rhIGFBP-3 | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | ROP of Stage 1 | 4 participants |
| rhIGF-1/rhIGFBP-3 | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | ROP of Stage 3+ | 6 participants |
| rhIGF-1/rhIGFBP-3 | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | ROP of Stage 0 | 14 participants |
| rhIGF-1/rhIGFBP-3 | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | ROP of Stage 2 | 17 participants |
| rhIGF-1/rhIGFBP-3 | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | Missing | 14 participants |
| rhIGF-1/rhIGFBP-3 | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | ROP of Stage 4 | 0 participants |
| Standard of Care (Control) | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | Missing | 10 participants |
| Standard of Care (Control) | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | ROP of Stage 4 | 0 participants |
| Standard of Care (Control) | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | ROP of Stage 0 | 24 participants |
| Standard of Care (Control) | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | ROP of Stage 1 | 4 participants |
| Standard of Care (Control) | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | ROP of Stage 2 | 13 participants |
| Standard of Care (Control) | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | ROP of Stage 3 | 3 participants |
| Standard of Care (Control) | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | ROP of Stage 3+ | 6 participants |
| Standard of Care (Control) | Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population | ROP of Stage 5 | 0 participants |
p-value: 0.0642CMH Row Mean Score Test
Secondary
Area Under Curve for Maximum Severity of ROP Stage (AUC for ROP)
Integration of the maximum severity of ROP stage and the duration of the time interval with respect to each retinal examination. AUC for the maximum severity of ROP was calculated using the trapezoidal rule. The area between each 2 visits was calculated by multiplying the average of the maximum severities of the 2 visits by the difference in days and analyzed using the van Elteren test. ROP is classified according to the International Classification and is subdivided into 5 stages (1-5) with higher values representing greater severity.
Time frame: Every 1-2 weeks starting at 31 weeks PMA/ EOS +/- 4 days
Population: Full analysis set with number of participants evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhIGF-1/rhIGFBP-3 | Area Under Curve for Maximum Severity of ROP Stage (AUC for ROP) | 47.95 ROP severity score*days | Standard Deviation 47.384 |
| Standard of Care (Control) | Area Under Curve for Maximum Severity of ROP Stage (AUC for ROP) | 32.17 ROP severity score*days | Standard Deviation 40.151 |
Secondary
Brain Development Assessed by Brain Volume at 40 Weeks PMA/EOS
Brain volume was measured using cerebral magnetic resonance imaging (MRI). Brain volume included cerebrospinal volume, gray matter volume, white matter volume, and total cerebellar volume
Time frame: 40 Weeks PMA/ (EOS) +/- 4 days
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhIGF-1/rhIGFBP-3 | Brain Development Assessed by Brain Volume at 40 Weeks PMA/EOS | Cerebrospinal Fluid Volume | 87.94 cubic centimeter | Standard Deviation 26.788 |
| rhIGF-1/rhIGFBP-3 | Brain Development Assessed by Brain Volume at 40 Weeks PMA/EOS | Gray Matter Volume | 206.34 cubic centimeter | Standard Deviation 31.797 |
| rhIGF-1/rhIGFBP-3 | Brain Development Assessed by Brain Volume at 40 Weeks PMA/EOS | White Matter Volume | 110.23 cubic centimeter | Standard Deviation 25.565 |
| rhIGF-1/rhIGFBP-3 | Brain Development Assessed by Brain Volume at 40 Weeks PMA/EOS | Total Cerebellar Volume | 18.27 cubic centimeter | Standard Deviation 5.302 |
| Standard of Care (Control) | Brain Development Assessed by Brain Volume at 40 Weeks PMA/EOS | Total Cerebellar Volume | 19.20 cubic centimeter | Standard Deviation 4.854 |
| Standard of Care (Control) | Brain Development Assessed by Brain Volume at 40 Weeks PMA/EOS | Cerebrospinal Fluid Volume | 93.70 cubic centimeter | Standard Deviation 25.54 |
| Standard of Care (Control) | Brain Development Assessed by Brain Volume at 40 Weeks PMA/EOS | White Matter Volume | 117.62 cubic centimeter | Standard Deviation 24.422 |
| Standard of Care (Control) | Brain Development Assessed by Brain Volume at 40 Weeks PMA/EOS | Gray Matter Volume | 221.98 cubic centimeter | Standard Deviation 33.827 |
Secondary
Number of Participants With Bronchopulmonary Dysplasia (BPD)
Severity of BPD as mild, moderate and severe were based on the National Institute of Child Health and Human Development (NICHD) guidelines for preterm infants born at gestational age (GA) less than (\<) 32 weeks. Mild: oxygen requirement during the first 28 days but in room air at PMA 36 weeks or discharge to home, whichever comes first. Moderate BPD: oxygen requirement during the first 28 days and oxygen \<30 percent (%) at PMA 36 weeks or discharge to home, whichever comes first. Severe BPD: oxygen requirement during the first 28 days and oxygen greater than equal (≥)30% through head hood or nasal canula, or continuous positive airway pressure, or mechanical ventilation, or high flow nasal cannula ≥2 L/min at PMA 36 weeks or discharge to home, whichever comes first.
Time frame: At 36 Weeks Post Menstrual Age
Population: FAS with participants evaluable for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rhIGF-1/rhIGFBP-3 | Number of Participants With Bronchopulmonary Dysplasia (BPD) | Unable to determine | 1 participants |
| rhIGF-1/rhIGFBP-3 | Number of Participants With Bronchopulmonary Dysplasia (BPD) | No BPD | 4 participants |
| rhIGF-1/rhIGFBP-3 | Number of Participants With Bronchopulmonary Dysplasia (BPD) | Mild | 23 participants |
| rhIGF-1/rhIGFBP-3 | Number of Participants With Bronchopulmonary Dysplasia (BPD) | Moderate | 9 participants |
| rhIGF-1/rhIGFBP-3 | Number of Participants With Bronchopulmonary Dysplasia (BPD) | Severe | 10 participants |
| Standard of Care (Control) | Number of Participants With Bronchopulmonary Dysplasia (BPD) | Severe | 22 participants |
| Standard of Care (Control) | Number of Participants With Bronchopulmonary Dysplasia (BPD) | Moderate | 5 participants |
| Standard of Care (Control) | Number of Participants With Bronchopulmonary Dysplasia (BPD) | No BPD | 4 participants |
| Standard of Care (Control) | Number of Participants With Bronchopulmonary Dysplasia (BPD) | Unable to determine | 2 participants |
| Standard of Care (Control) | Number of Participants With Bronchopulmonary Dysplasia (BPD) | Mild | 16 participants |
Secondary
Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse event was defined as the onset of any AE or if the severity of a pre-existing AE worsened any time on or after the date of first dose of investigational product.
Time frame: Day 0 to 40 Weeks Post Menstrual Age (EOS)
Population: Safety Analysis Set (SAF) included all randomized participants who received the study drug and participants in the control group who received standard of care, and for whom at least 1 safety assessment was completed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rhIGF-1/rhIGFBP-3 | Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) | Participants with TEAE | 60 participants |
| rhIGF-1/rhIGFBP-3 | Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) | Participants with TESAE | 48 participants |
| Standard of Care (Control) | Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) | Participants with TEAE | 60 participants |
| Standard of Care (Control) | Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) | Participants with TESAE | 37 participants |
Secondary
Percentage of Participants With Intraventricular Hemorrhage (IVH)
Development of intraventricular hemorrhage was assessed by cerebral ultrasound and coded as a binary endpoint (presence or absence of IVH).
Time frame: Day 0 to 40 Weeks Post Menstrual Age (EOS)
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rhIGF-1/rhIGFBP-3 | Percentage of Participants With Intraventricular Hemorrhage (IVH) | Yes | 19.67 percentage of participants |
| rhIGF-1/rhIGFBP-3 | Percentage of Participants With Intraventricular Hemorrhage (IVH) | No | 80.33 percentage of participants |
| Standard of Care (Control) | Percentage of Participants With Intraventricular Hemorrhage (IVH) | No | 70.0 percentage of participants |
| Standard of Care (Control) | Percentage of Participants With Intraventricular Hemorrhage (IVH) | Yes | 30.0 percentage of participants |
Secondary
Percentage of Participants With Maximum Severity of ROP Stage Greater Than or Equal to 3 at Any Time During the 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.
Time frame: Day 0 to 40 Weeks Post Menstrual Age (EOS)
Population: FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rhIGF-1/rhIGFBP-3 | Percentage of Participants With Maximum Severity of ROP Stage Greater Than or Equal to 3 at Any Time During the Study | Yes | 25.53 Percentage of participants |
| rhIGF-1/rhIGFBP-3 | Percentage of Participants With Maximum Severity of ROP Stage Greater Than or Equal to 3 at Any Time During the Study | No | 74.47 Percentage of participants |
| Standard of Care (Control) | Percentage of Participants With Maximum Severity of ROP Stage Greater Than or Equal to 3 at Any Time During the Study | Yes | 18.00 Percentage of participants |
| Standard of Care (Control) | Percentage of Participants With Maximum Severity of ROP Stage Greater Than or Equal to 3 at Any Time During the Study | No | 82.00 Percentage of participants |
Secondary
Percentage of Serum IGF-1 Concentrations Falling Within Target Range After Infusion of rhIGF-1/rhIGFBP-3
Serum samples were collected from treated and control participants for quantification of IGF-1 using validated immunoassays. Target range of serum IGF-1 was 28-109 mcg/L. The percentage of serum IGF-1 levels across treated participants that fall within the range was reported.
Time frame: Day 0 to 40 Weeks Post Menstrual Age (EOS)
Population: FAS was analysed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rhIGF-1/rhIGFBP-3 | Percentage of Serum IGF-1 Concentrations Falling Within Target Range After Infusion of rhIGF-1/rhIGFBP-3 | 66.23 percentage of serum concentration |
| Standard of Care (Control) | Percentage of Serum IGF-1 Concentrations Falling Within Target Range After Infusion of rhIGF-1/rhIGFBP-3 | 6.28 percentage of serum concentration |
Secondary
Rate of Change in Body Weight
The rate of change is the rate of specific body weight change per day in kilogram (kg).
Time frame: Day 0 to 40 Weeks Post Menstrual Age (EOS)
Population: FAS
| Arm | Measure | Value (MEAN) |
|---|---|---|
| rhIGF-1/rhIGFBP-3 | Rate of Change in Body Weight | 0.021 kilogram per day (kg/day) |
| Standard of Care (Control) | Rate of Change in Body Weight | 0.023 kilogram per day (kg/day) |
Secondary
Rate of Change in Head Circumference
The rate of change is the head circumference change per day in centimetre (cm).
Time frame: Day 0 to 40 Weeks Post Menstrual Age (EOS)
Population: FAS
| Arm | Measure | Value (MEAN) |
|---|---|---|
| rhIGF-1/rhIGFBP-3 | Rate of Change in Head Circumference | 0.115 cm/day |
| Standard of Care (Control) | Rate of Change in Head Circumference | 0.119 cm/day |
Secondary
Rate of Change in Length
The rate of change is the length change per day in centimeter (cm).
Time frame: Day 0 to 40 Weeks Post Menstrual Age (EOS)
Population: FAS
| Arm | Measure | Value (MEAN) |
|---|---|---|
| rhIGF-1/rhIGFBP-3 | Rate of Change in Length | 0.141 centimeter per day (cm/day) |
| Standard of Care (Control) | Rate of Change in Length | 0.156 centimeter per day (cm/day) |
Secondary
Serum Concentrations of Acid Labile Sub-unit (ALS) After Intravenous (IV) Infusion of rhIGF-1/rhIGFBP-3
Time frame: Day 7 and Week 40 Post Menstrual Age
Population: FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhIGF-1/rhIGFBP-3 | Serum Concentrations of Acid Labile Sub-unit (ALS) After Intravenous (IV) Infusion of rhIGF-1/rhIGFBP-3 | Day 7 | 411.9 microgram per liter | Standard Deviation 237.91 |
| rhIGF-1/rhIGFBP-3 | Serum Concentrations of Acid Labile Sub-unit (ALS) After Intravenous (IV) Infusion of rhIGF-1/rhIGFBP-3 | Week 40 | 1804.6 microgram per liter | Standard Deviation 629.61 |
| Standard of Care (Control) | Serum Concentrations of Acid Labile Sub-unit (ALS) After Intravenous (IV) Infusion of rhIGF-1/rhIGFBP-3 | Day 7 | 500.3 microgram per liter | Standard Deviation 350.59 |
| Standard of Care (Control) | Serum Concentrations of Acid Labile Sub-unit (ALS) After Intravenous (IV) Infusion of rhIGF-1/rhIGFBP-3 | Week 40 | 2114.3 microgram per liter | Standard Deviation 941.94 |
Secondary
Serum Concentrations of IGFBP-3 After Intravenous (IV) Infusion of rhIGF-1/rhIGFBP-3
Time frame: Day 0 and Week 40 Post Menstrual Age
Population: FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhIGF-1/rhIGFBP-3 | Serum Concentrations of IGFBP-3 After Intravenous (IV) Infusion of rhIGF-1/rhIGFBP-3 | Day 0 | 494.2 microgram per liter | Standard Deviation 200.38 |
| rhIGF-1/rhIGFBP-3 | Serum Concentrations of IGFBP-3 After Intravenous (IV) Infusion of rhIGF-1/rhIGFBP-3 | Week 40 | 830.1 microgram per liter | Standard Deviation 200.17 |
| Standard of Care (Control) | Serum Concentrations of IGFBP-3 After Intravenous (IV) Infusion of rhIGF-1/rhIGFBP-3 | Day 0 | 469.9 microgram per liter | Standard Deviation 180.52 |
| Standard of Care (Control) | Serum Concentrations of IGFBP-3 After Intravenous (IV) Infusion of rhIGF-1/rhIGFBP-3 | Week 40 | 882.1 microgram per liter | Standard Deviation 274.43 |
Secondary
Time to Discharge From Neonatal Intensive Care (TDNIC)
Time frame: Day 0 to 40 Weeks Post Menstrual Age (EOS)
Population: FAS with number of participants evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| rhIGF-1/rhIGFBP-3 | Time to Discharge From Neonatal Intensive Care (TDNIC) | 82.00 Days |
| Standard of Care (Control) | Time to Discharge From Neonatal Intensive Care (TDNIC) | 74.00 Days |