E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Retinopathy of Prematurity (ROP) |
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E.1.1.1 | Medical condition in easily understood language |
ROP is a rare disorder of the developing retinal blood vessels and retinal neurons of the preterm infant and is one of the leading causes of preventable blindness in children |
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E.1.1.2 | Therapeutic area | Body processes [G] - Ocular Physiological Phenomena [G14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives of this study are:
- To evaluate the long-term efficacy outcomes following short-term exposure to rhIGF-1/rhIGFBP-3 versus standard neonatal care in Study ROPP-2008-01 (Section D) as assessed by ROP-associated visual outcomes
- To evaluate the long-term safety outcomes following short-term exposure to rhIGF-1/rhIGFBP-3 versus standard neonatal care in Study ROPP-2008-01 (Section D) |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to evaluate the effect following short-term exposure to rhIGF-1/rhIGFBP-3 versus standard neonatal care in Study ROPP-2008-01 (Section D) on: Growth parameters; Cognitive development; Physical development; Child behavior; Pulmonary morbidity; Survival; Health-related quality of life (HRQoL); Health utility; Health care resource use (HCRU)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Each subject must meet the following criteria to be enrolled in this study.
1. Subject was randomized in Study ROPP-2008-01, Section D
2. Subject’s parent or legally authorized representative(s) must provide written informed consent prior to performing any study-related activities. Study-related activities are any procedures that would not have been performed during normal management of the subject. |
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E.4 | Principal exclusion criteria |
Subjects who meet any of the following criteria will be excluded from the study.
1. 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 the interpretation of results
2. The subject or subject’s parent or legally authorized representative(s) is unable to comply
with the protocol as determined by the Investigator |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoints of this study are:
- Visual acuity as assessed by an age appropriate method
- Ocular alignment and ocular motor examination in primary gaze and in as many of 9 positions of gaze as possible as assessed by corneal light reflex and by the cover test
- Assessment of nystagmus by observation
- Refraction as assessed by retinoscopy with cycloplegia
- Stereoacuity as assessed with the Lang Stereotest |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
will vary depending upon age at enrollment, but subjects will not be followed beyond age 5.5 years corrected age (CA) |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints of this study are:
- Growth parameters including body weight, body length (or height), and head circumference
- Cognitive development as assessed by the following standardized, age-appropriate tools:
o Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)
o Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV)
- Physical development as assessed by standardized, age appropriate tools including physical exam, neurological examination for assessment of cerebral palsy, and hearing assessment
- Child behavior as assessed by the following:
o Vineland Adaptive Behavior Scales, Second Edition (VABS-II)
o Child Behavior Checklist (CBCL; 1 ½ to 5)
o Attention Deficit/Hyperactivity Disorder Rating Scale-fourth edition (ADHD RS-IV) for the assessment of symptoms of attention deficit/hyperactivity disorder (ADHD)
o Social Communication Questionnaire (SCQ) for screening of Autism Spectrum Disorder (ASD)
- Pulmonary morbidity data (eg, hospitalizations, emergency room [ER] visits, pulmonary medications)
- Cerebral magnetic resonance imaging (MRI): Participation in the MRI
assessment is optional and has no impact on participating in the main matter, corpus callosum, frontal lobes, cerebellum and total volume will
be analysed for the purposes of the study)
- Survival as assessed by death during the study due to any cause
- Blood pressure, heart rate and respiratory rate will be measured at the 5 year CA visit.
The health economic outcome research endpoints of this study are:
- Health-related quality of life (HRQoL) will be assessed by the Pediatric Quality of Life Inventory (PedsQL™) Scales appropriate for the child's age of development with the Total Scale Score and 5 domains within Physical Health (Physical Functioning and Physical Symptoms) and Psychosocial Health Scores (Emotional, Social, and Cognitive Functioning, respectively)
- Health status (eg, health utility) will be measured by the Health Status Classification System-Preschool (HSCS-PS) and the Health Utilities Index
Mark 2 (HUI2) and Mark 3 (HUI3)
- Resource use associated with inpatient visits, outpatient visits, medical utilization and
pharmacy utilization will be assessed
The safety endpoints of this study are:
- Physical examination including tonsil examination
- Adverse events (AEs), as follows:
o those considered related to rhIGF-1/rhIGFBP-3 (as administered in Study ROPP-2008-01, Section D)
o those considered related to procedures performed in this study (Study SHP-607-201)
o specified targeted medical events regardless of causality
o fatal SAEs regardless of causality
- Cardiac size as assessed by echocardiogram
- Kidney and spleen size and any other gross abnormalities as assessed by abdominal ultrasound
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
will vary depending upon age at enrollment, but subjects will not be followed beyond age 5.5 years corrected age (CA) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
long-term developmental outcome study |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
long-term developmental outcome study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Italy |
Netherlands |
Poland |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Duration for an individual subject’s participation in the study will vary depending upon age at enrollment, but subjects will not be followed beyond age 5.5 years corrected age (CA) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |