Long-term Outcome of Children Enrolled in Study ROPP-2008-01 Previously Treated With rhIGF-1/rhIGFBP-3 for the Prevention of Retinopathy of Prematurity (ROP) or Who Received Standard Neonatal Care
Overview
- Phase
- Phase 2
- Intervention
- rhIGF-1/rhIGFBP-3
- Conditions
- Retinopathy of Prematurity (ROP)
- Sponsor
- Shire
- Enrollment
- 76
- Locations
- 16
- Primary Endpoint
- Number of Participants With Visual Acuity as Assessed by an Age-appropriate Method at 6 Months Corrected Age (CA)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The main purpose of this study is to evaluate the long-term efficacy and safety outcomes following short-term exposure to rhIGF-1/rhIGFBP-3 versus standard neonatal care in Study ROPP-2008-01 (NCT01096784).
Detailed Description
Long-term Safety and Efficacy Outcome Study Comparing Children Previously Enrolled in Study ROPP-2008-01 for the Prevention of Retinopathy of Prematurity (ROP)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant was randomized in Study ROPP-2008-01 Section D (NCT01096784).
- •Participants 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 participant.
Exclusion Criteria
- •Any other condition or therapy that, in the Investigator's opinion, may pose a risk to the Participant or interfere with the participants ability to be compliant with this protocol or interfere with the interpretation of results.
- •The participant or participants parent or legally authorized representative(s) is unable to comply with the protocol as determined by the Investigator.
Arms & Interventions
Antecedent Standard of Care
Participants who were treated with standard neonatal care in study ROPP-2008-01 (NCT01096784) were enrolled in this group for assessment of rhIGF-1/rhIGFBP-3 long-term efficacy and safety outcomes.
Intervention: rhIGF-1/rhIGFBP-3
Antecedent rhIGF-1/rhIGFBP-3
Participants who were treated with rhIGF-1/rhIGFBP-3 in study ROPP-2008-01 (NCT01096784) were enrolled in this group for assessment of rhIGF-1/rhIGFBP-3 long-term efficacy and safety outcomes.
Intervention: rhIGF-1/rhIGFBP-3
Outcomes
Primary Outcomes
Number of Participants With Visual Acuity as Assessed by an Age-appropriate Method at 6 Months Corrected Age (CA)
Time Frame: At 6 Months CA
Standard age-appropriate methods were used to assess visual acuity (how well a participant sees at different distances) with teller acuity cards, LEA symbols test and Charts. It was categorized as following: normal (measurable acuity \>= 20/40 or \>= 15 cycles/degree); below normal (20/200 \<= measurable acuity \< 20/40 or 3 cycles/degree \<= measurable acuity \< 15 cycles/degree); poor (measurable acuity \<= 20/200 or \<= 3 cycles/degree). Corrected Age (weeks) was defined as Chronological Age (weeks) - 40 + Gestational Age (weeks) in this study.
Number of Participants With Visual Acuity as Assessed by an Age-appropriate Method at 12 Months CA
Time Frame: At 12 Months CA
Standard age-appropriate methods were used to assess visual acuity (how well a participant sees at different distances) with teller acuity cards, LEA symbols test and Charts. It was categorized as following: normal (measurable acuity \>= 20/40 or \>= 15 cycles/degree); below normal (20/200 \<= measurable acuity \< 20/40 or 3 cycles/degree \<= measurable acuity \< 15 cycles/degree); poor (measurable acuity \<= 20/200 or \<= 3 cycles/degree). Corrected Age (weeks) was defined as Chronological Age (weeks) - 40 + Gestational Age (weeks) in this study.
Number of Participants With Visual Acuity as Assessed by an Age-appropriate Method at 4.75 Years CA
Time Frame: At 4.75 Years CA
Standard age-appropriate methods were used to assess visual acuity (how well a participant sees at different distances) with teller acuity cards, LEA symbols test and Charts. It was categorized as following: normal (measurable acuity \>= 20/40 or \>= 15 cycles/degree); below normal (20/200 \<= measurable acuity \< 20/40 or 3 cycles/degree \<= measurable acuity \< 15 cycles/degree); poor (measurable acuity \<= 20/200 or \<= 3 cycles/degree). Corrected Age (weeks) was defined as Chronological Age (weeks) - 40 + Gestational Age (weeks) in this study.
Number of Participants With Oculomotor Examination (Motility) and Ocular Alignment (Assessed by Corneal Light Reflex and Cover Test) at 5-Years CA
Time Frame: At 5 Years CA
Ocular alignment was assessed in primary gaze by comparing the position of the corneal light reflection in left eye and right eye (corneal light reflection assessment). Presence or absence of strabismus was recorded in primary gaze and in as many of the 9 positions of gaze as feasible with the cover test assessment of refixation movement. Extraocular muscle over action or deficiency was recorded. Ocular motility referred to eye movements governed by the 6 extraocular muscles in each eye. It was assessed by examiner observation of the participants ability to abduct, adduct, supra, and inferoduct each eye. Ocular alignment and motility included the presence or absence of strabismus (classified as Esotropia, Exotropia, Hypertropia, Hypotropia) was recorded. Number of participants with combined data for ocular alignment and oculomotor examination (motility) assessed by corneal light reflex and by the cover test at 5-Years CA were reported.
Refraction With Cycloplegia as Assessed by Retinoscopy at 12 Month CA
Time Frame: At 12 Months CA
Refraction was a measure of the lens power required for a focused image on the retina. Refraction with cycloplegia was measured and recorded in diopters for each eye individually (left eye and right eye). Refraction with cycloplegia performed as part of the corrective lens determination procedure included measurements of sphere, cylinder, axis, and prism for each individual eye (left eye and right eye). For sphere, the negative values are summarized as 'nearsighted', and the positive values (including sphere of 0.00) are summarized as 'farsighted'.
Refraction With Cycloplegia as Assessed by Retinoscopy at 4.75 Years CA
Time Frame: At 4.75 Years CA
Refraction was a measure of the lens power required for a focused image on the retina. Refraction with cycloplegia was measured and recorded in diopters for each eye individually (left eye and right eye). Refraction with cycloplegia performed as part of the corrective lens determination procedure included measurements of sphere, cylinder, axis, and prism for each individual eye (left eye and right eye). For sphere, the negative values are summarized as 'nearsighted', and the positive values (including sphere of 0.00) are summarized as 'farsighted'.
Number of Participants With Stereoacuity as Assessed With the Lang Stereotest At 5 Years CA
Time Frame: At 5 Years CA
Stereoacuity, a measure of depth perception, was assessed using the Lang Stereotest. Number of participants with presence and absence of stereopsis (the ability to perceive depth and 3-dimensional structure) was reported.
Number of Participants With Visual Acuity as Assessed by an Age-appropriate Method at 20 Months CA
Time Frame: At 20 Months CA
Standard age-appropriate methods were used to assess visual acuity (how well a participant sees at different distances) with teller acuity cards, LEA symbols test and Charts. It was categorized as following: normal (measurable acuity \>= 20/40 or \>= 15 cycles/degree); below normal (20/200 \<= measurable acuity \< 20/40 or 3 cycles/degree \<= measurable acuity \< 15 cycles/degree); poor (measurable acuity \<= 20/200 or \<= 3 cycles/degree). Corrected Age (weeks) was defined as Chronological Age (weeks) - 40 + Gestational Age (weeks) in this study.
Number of Participants With Visual Acuity as Assessed by an Age-appropriate Method at 5 Years CA
Time Frame: At 5 Years CA
Standard age-appropriate methods were used to assess visual acuity (how well a participant sees at different distances) with teller acuity cards, LEA symbols test and Charts. It was categorized as following: normal (measurable acuity \>= 20/40 or \>= 15 cycles/degree); below normal (20/200 \<= measurable acuity \< 20/40 or 3 cycles/degree \<= measurable acuity \< 15 cycles/degree); poor (measurable acuity \<= 20/200 or \<= 3 cycles/degree). Corrected Age (weeks) was defined as Chronological Age (weeks) - 40 + Gestational Age (weeks) in this study.
Number of Participants With Nystagmus at 5 Years CA
Time Frame: At 5 Years CA
Nystagmus was observed during the ocular alignment assessments. Presence and absence of nystagmus was reported at 5 Years CA.
Number of Participants With Visual Acuity as Assessed by an Age-appropriate Method at 24 Months CA
Time Frame: At 24 Months CA
Standard age-appropriate methods were used to assess visual acuity (how well a participant sees at different distances) with teller acuity cards, LEA symbols test and Charts. It was categorized as following: normal (measurable acuity \>= 20/40 or \>= 15 cycles/degree); below normal (20/200 \<= measurable acuity \< 20/40 or 3 cycles/degree \<= measurable acuity \< 15 cycles/degree); poor (measurable acuity \<= 20/200 or \<= 3 cycles/degree). Corrected Age (weeks) was defined as Chronological Age (weeks) - 40 + Gestational Age (weeks) in this study.
Number of Participants With Oculomotor Examination (Motility) and Ocular Alignment (Assessed by Corneal Light Reflex and Cover Test) at 12 Months CA
Time Frame: At 12 Months CA
Ocular alignment was assessed in primary gaze by comparing the position of the corneal light reflection in left eye and right eye (corneal light reflection assessment). Presence or absence of strabismus was recorded in primary gaze and in as many of the 9 positions of gaze as feasible with the cover test assessment of refixation movement. Extraocular muscle over action or deficiency was recorded. Ocular motility referred to eye movements governed by the 6 extraocular muscles in each eye. It was assessed by examiner observation of the participants ability to abduct, adduct, supra, and inferoduct each eye. Ocular alignment and motility included the presence or absence of strabismus (classified as Esotropia \[inward turn of the eye\], Exotropia \[outward turn of the eye\], Hypertropia \[upward turn of the eye\], Hypotropia \[downward turn of the eye\]) was recorded. Number of participants with combined data for ocular alignment and oculomotor examination (motility) at 12 months CA were reported.
Number of Participants With Oculomotor Examination (Motility) and Ocular Alignment (Assessed by Corneal Light Reflex and Cover Test) at 24 Months CA
Time Frame: At 24 Months CA
Ocular alignment was assessed in primary gaze by comparing the position of the corneal light reflection in left eye and right eye (corneal light reflection assessment). Presence or absence of strabismus was recorded in primary gaze and in as many of the 9 positions of gaze as feasible with the cover test assessment of refixation movement. Extraocular muscle over action or deficiency was recorded. Ocular motility referred to eye movements governed by the 6 extraocular muscles in each eye. It was assessed by examiner observation of the participants ability to abduct, adduct, supra, and inferoduct each eye. Ocular alignment and motility included the presence or absence of strabismus (classified as Esotropia, Exotropia, Hypertropia, Hypotropia) was recorded. Number of participants with combined data for ocular alignment and oculomotor examination (motility) assessed by corneal light reflex and by the cover test at 24 months CA were reported.
Number of Participants With Nystagmus at 12 Months CA
Time Frame: At 12 Months CA
Nystagmus was observed during the ocular alignment assessments. Presence and absence of nystagmus was reported at 12 Months CA.
Number of Participants With Nystagmus at 24 Months CA
Time Frame: At 24 Months CA
Nystagmus was observed during the ocular alignment assessments. Presence and absence of nystagmus was reported at 24 Months CA.
Refraction With Cycloplegia as Assessed by Retinoscopy at 6 Months CA
Time Frame: At 6 Months CA
Refraction was a measure of the lens power required for a focused image on the retina. Refraction with cycloplegia was measured and recorded in diopters for each eye individually (left eye and right eye). Refraction with cycloplegia performed as part of the corrective lens determination procedure included measurements of sphere, cylinder, axis, and prism for each individual eye (left eye and right eye). For sphere, the negative values are summarized as 'nearsighted', and the positive values (including sphere of 0.00) are summarized as 'farsighted'.
Refraction With Cycloplegia as Assessed by Retinoscopy at 20 Month CA
Time Frame: At 20 Months CA
Refraction was a measure of the lens power required for a focused image on the retina. Refraction with cycloplegia was measured and recorded in diopters for each eye individually (left eye and right eye). Refraction with cycloplegia performed as part of the corrective lens determination procedure included measurements of sphere, cylinder, axis, and prism for each individual eye (left eye and right eye). For sphere, the negative values are summarized as 'nearsighted', and the positive values (including sphere of 0.00) are summarized as 'farsighted'.
Number of Participants With Adverse Events (AEs)
Time Frame: From start of study up to end of study (up to 6.5 years)
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.
Secondary Outcomes
- Change From Baseline (12 Months CA) in Cognitive Development as Assessed by Bayley Scales of Infant and Toddler Development (BSID-III) Composite Scores at 24 Months CA(Baseline (12 Months CA), 24 Months CA)
- Cognitive Development as Assessed by Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) Full Scale at 5 Years CA(At 5 Years CA)
- Number of Participants With Abnormal Physical Examination(From start of study drug administration up to end of study (up to 6.5 years))
- Number of Participants With Child Behaviour as Assessed by Child Behaviour Checklist (CBCL) Based on T-Score Clinical Categories(At 24 Months CA and 5 Years CA)
- Change From Baseline (3 Months CA) in Pediatric Quality of Life Inventory (PedsQL™) Scale: Infant Scale(Baseline (3 Months CA) up to 6 Months CA, 12 Months CA and 24 Months CA)
- Health Care Resource Use (HCRU)(At 3 Months CA, 6 Months CA, 12 Months CA, 24 Months CA, 3 Years CA, 4 Years CA and 5 Years CA)
- Change From Baseline in Body Weight Z-score(Baseline, 6 Months CA, 12 Months CA, 24 Months CA and 5 Years CA)
- Change From Baseline in Height Z-score(Baseline, 6 Months CA, 12 Month CA, 24 Months CA and 5 Years CA)
- Change From Baseline in Head Circumference Z-score(Baseline, 6 Months CA, 12 Months CA and 24 Months CA)
- Number of Participants With Normal and Abnormal Hearing Screening Status(At 6 Months CA and 5 Years CA)
- Change From Baseline (6 Months CA) in Child Behavior as Assessed by Vineland Adaptive Behaviour Scales (VABS-II)(Baseline (6 Months CA), 12 Months CA, 24 Months CA, and 5 Year CA)
- Health Care Resource Utilization (HCRU): Duration of Hospitalization(At 3 Months CA, 6 Months CA, 12 Months CA , 24 Months CA, 3 Years CA, 4 Years CA and 5 Years CA)
- Number of Participants Diagnosed With Neurological Examination for Cerebral Palsy (CP) by Neurological Examination at 24 Months CA(At 24 Months CA)
- Number of Participants With Health Status Measured by the Health Status Classification System-Preschool (HSCS-PS)(At 24 Months CA, 3 Years CA, 4 Years CA and 5 Years CA)
- Child Behavior as Assessed by Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) Based on Total Score(At 5 Years CA)
- Child Behavior as Assessed by Social Communication Questionnaire (SCQ)(At 5 Years CA)
- Number of Participants With Pulmonary Morbidity(At 6 Months CA, 12 Months CA and 24 Months CA)
- Number of Participants With Survival Status(From start of study drug administration up to end of study (up to 6.5 years))
- Change From Baseline (24 Months CA) in Pediatric Quality of Life Inventory (PedsQL™) Scale: Generic Core Scale (GCS) Total Score(Baseline (24 Months CA), up to 3 Years CA, 4 Years CA and 5 Years CA)
- Health Status Measured by the Health Utilities Index (HUI) Mark 2 and 3(At 5 Years CA)
- Health Care Resource Utilization (HCRU): Number of Visits to Emergency Department(At 3 Months CA, 6 Months CA, 12 Months CA , 24 Months CA, 3 Years CA, 4 Years CA and 5 Years CA)
- Health Care Resource Utilization (HCRU): Number of Participants Who Required Prescription Eyeglasses and Educational Support(At 3 Months CA, 6 Months CA, 12 Months CA, 24 Months CA, 3 Years CA, 4 Years CA and 5 Years CA)