Safety and Efficacy Outcomes Following Previously Administered Short-Term Treatment With SHP607 in Extremely Premature Infants

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate long-term safety and efficacy outcomes following previously administered short-term exposure to SHP607, as compared to a standard neonatal care group.

Detailed Description
-----------------
In this long-term follow-up study, participants who enrolled in SHP607-202 (NCT03253263) will be followed from 12 months corrected age (CA) through 60 months CA. Participants will not receive any investigational product in this study.

Official Title
-----------------
Long-Term Safety and Efficacy Outcomes Following Previously Administered Short-Term Treatment With SHP607 in Extremely Premature Infants

Conditions
-----------------
Retinopathy of Prematurity (ROP), Intraventricular Hemorrhage, Bronchopulmonary Dysplasia, Chronic Lung Disease of Prematurity

Intervention / Treatment
-----------------
* Other: No Intervention


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants who were randomized into Study SHP607-202 (NCT03253263). Participants who were randomized, but did not complete Study SHP607-202 (NCT03253263) must be at least 12 months CA. Written informed consents (and assents, if applicable) must be signed and dated by the participant's parent(s)/legally authorized representative(s) prior to any study-related procedures. The informed consent and any assents for underage parents must be approved by the institutional review board (IRB)/independent ethics committee (IEC). Exclusion Criteria: - Participants are excluded from the study if the participant or participant's parent(s)/legally authorized representative(s) is/are unable to comply with the protocol or is/are unlikely to be available for long-term follow-up as determined by the investigator.

Ages Eligible for Study
-----------------
Minimum Age: 12 Months
Maximum Age: 24 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SHP607 250 mcg/kg/24 hours<br>Participants who received 250 micrograms per kilogram per 24 hours (mcg/kg/24 hours) in the previous study SHP607-202 (NCT03253263) will be followed into this long-term study SHP607-203. | Other: No Intervention<br>* This is a non-interventional study.<br>|
| SHP607 400 mcg/kg/24 hours<br>Participants who received 400 mcg/kg/24 hours in the previous study SHP607-202 (NCT03253263) will be followed into this long-term study SHP607-203. | Other: No Intervention<br>* This is a non-interventional study.<br>|
| Standard Neonatal Care<br>Participants who received standard neonatal care in the previous study SHP607-202 (NCT03253263) will be followed into this long-term study SHP607-203. | Other: No Intervention<br>* This is a non-interventional study.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Emergency Room Visits | Number of emergency room visits associated with a respiratory diagnosis will be reported. | 12 months CA through 60 months CA | 
| Number of Hospitalizations | Number of hospitalizations associated with a respiratory diagnosis will be reported. | 12 months CA through 60 months CA | 
| Incidence of Signs and Symptoms of Respiratory Disease | Incidence of signs and symptoms of respiratory disease (yes/no) is assessed by recording episodes of wheezing, coughing, and respiratory medication. | 12 months CA through 60 months CA | 
| Number of Days of Respiratory Medication Use | Number of days of respiratory medication use (for example, bronchodilators, steroids, leukotriene inhibitors, diuretics) will be reported. | 12 months CA through 60 months CA | 
| Total Number of Days on Home Respiratory Technology use | Total number of days on home respiratory technology use (for example, home oxygen, continuous positive airway pressure [CPAP], tracheostomy) will be reported. | 12 months CA through 60 months CA | 
| Number of Participants With Adverse Events (AEs) | An adverse event (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. | 12 months CA through 60 months CA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth Parameters: Body Weight | Body weight is measured in kilograms (kg) without shoes and with light clothing using a calibrated scale. | At 12, 24, and 60 months CA | 
| Growth Parameters: Body Length | Body length is a supine measurement from the top of the head to the sole of the foot with the participant lying on the back with hips and knees extended. | At 12 and 24 months CA | 
| Growth Parameters: Height | Height is a measure of participant from head to foot (standing measure). A stadiometer should be utilized for measurement of height. | At 60 months CA | 
| Growth parameters: Head circumference | Head circumference or occipital frontal circumference is measured over the occiput and just above the supraorbital ridge, which is the largest circumference of the head. | At 12 and 24 months CA | 
| Physical Development as Assessed by Physical Examination | Physical examinations will include a review of the participant's general appearance. | At 12, 24, and 60 months CA | 
| Physical Development as Assessed by Neurological Examination for Assessment of Cerebral Palsy | Neurological examination for the diagnosis of cerebral palsy (CP) will be conducted. Neurologic examinations for the diagnosis of CP will be conducted by physicians including assessment of motor function, strength and development, muscle tone, and postural and movement abnormalities. | At 12, 24, and 60 months CA | 
| Physical Development as Assessed by Visual Acuity | Visual acuity is a measure of how well a participant sees at different distances. It will be categorized as the following: normal (measurable acuity greater than or equal to [>=] 20/40); below normal (20/200 less than or equal to [<=] measurable acuity <20/40); poor (measurable acuity <=20/200); blind/low vision (only the ability to detect the 2.2 centimeter [cm] wide stripes on the low-vision Teller acuity card and at any location in the visual field). | At 12, 24, and 60 months CA | 
| Cognitive Development Assessed by Bayley Scales of Infant and Toddler Development (BSID-III) | The BSID-III will be used to assess cognitive, motor, and language skills, and is applicable to children aged 1-42 months. The BSID-III is an assessment tool designed to measure a young child's skills in the 3 core areas of development: cognitive, language, and motor. There are 5 subscales, the cognitive subscale (Score range: 55-145) stands alone while the 2 language subscales (expressive and receptive) combine to make a total language score (Range: 47-153) and the 2 motor subtests (fine and gross motor) form a combined motor scale (Range: 46-154). A positive value indicates improvement. | At 24 months CA | 
| Cognitive Development Quotient Assessed by Kyoto Scale of Psychological Development (KSPD) | KSPD is a alternative scale to the BSID and used to assess cognitive, motor, and language skills at Japan sites only. The KSPD is a validated neurodevelopmental outcome assessment that is standardized for Japanese children and has been evaluated in comparison to BSID in the assessment of developmental characteristics of very low birth weight Japanese infants. The KSPD is designed to measure a young child's skills in three domains of development: Cognitive-Adaptive (non-verbal reasoning or visuospatial perception), Language-Social (interpersonal relationships, socialization, verbal abilities), and Postural-Motor (fine and gross motor functions). The scale consists of 328 items covering a Cognitive-Adaptive area, Language-Social area, and Postural-Motor area. For each of the three areas, a sum score is converted to a Developmental Quotient (dividing the developmental age by the chronological age and then multiplying the quotient by 100). A positive value indicates improvement. | At 24 months CA | 
| Cognitive Development Assessed by Wechsler Preschool and Primary Scale of Intelligence (WPPSI) | The WPPSI is a measure of general cognitive development in children that has components of both verbal and non-verbal tasks. It is applicable to preschoolers and young children aged 2 years +6 months to 7 years +7 months, and is a direct assessment of a child's cognitive skills. The standard score For the WPPSI ranges from Below 70 (extremely low) to above 130 (very superior). | At 60 months CA | 
| Gross Motor Function Assessed by Gross Motor Function Measure-88 (GMFM-88) | The GMFM-88 item scores is used to calculate a domain-specific percent score for each of the 5 GMFM-88 dimensions, which are the following: Lying and rolling; Sitting; Crawling and kneeling; Standing; Walking, running, and jumping. Each of the 88 items is rated on a 4-point scale: 0=does not initiate; 1=initiates; 2=partially completes; and 3=completes. The GMFM-88 total scores range from 0% (no mobility) to a score of 100%. The test is considered to be appropriate for children whose motor skills are at or below those of a 5-year-old child without any motor disability. The GMFM-88 will be administered at 24 months CA. GMFM-88 Sections D (Standing) and E (Walking, Running and Jumping) only will be administered at 5 years CA. | At 24 and 60 months CA | 
| Childhood Behavior Assessed by Vineland Adaptive Behavior Scales (VABS-III) | The VABS-III test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following 4 key domains: communication, daily living skills, socialization, and motor skills. The score ranges from 20 to 140 on which higher scores indicate a higher level of better behavior. | At 24 and 60 months CA | 
| Childhood Behavior Assessed by Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS-V) | The ADHD-RS-V measures the behaviors of children with Attention-Deficit/Hyperactivity Disorder (ADHD). It consists of 18 items designed to reflect current symptomatology of ADHD based on DSM-V criteria. Each item is scored from a range of 0 (reflecting no symptoms) to 3 (reflecting severe symptoms) with total scores ranging from 0-54. The 18 items are grouped into 2 subscales: hyperactivity-impulsivity (even numbered items 2-18) and inattention (inattentiveness) (odd numbered items 1-17). | At 60 months CA | 
| Childhood Behavior Assessed by Social Communication Questionnaire (SCQ) | The SCQ is a brief instrument that helps evaluate communication skills and social functioning in children that can be used for screening for autism or autism spectrum disorders (ASD) in the general population. The score ranges from 0 to 39, with a cut off of greater than (>) 15 indicating ASD. | At 60 months CA | 
| Health Related Quality of Life (HRQoL) Assessed by the Pediatric Quality of Life Inventory (PedsQL) Scales | HRQoL will be assessed via the validated Pediatric Quality of Life Inventory (PedsQL) Scales appropriate for the child's age of development. The following scales will be used in this study: Infant Scale for ages 13-24 months (45 Items); Toddler Scale for 2-4 years of age (21 Items); Young Child Scale for 5-7 years of age (23 Items). Scores are transformed to a 0 to 100 scale. Higher scores indicate better quality of life. | At 24, 36, 48, and 60 months CA | 
| Health Status Measured by the Health Utilities Index 2/3 | The Health Utilities Index (HUI) is a family of generic health profiles and preference-based systems used for measuring health status, reporting HRQoL, and producing utility scores. The HUI 2/3 system contains a number of attributes/domains to classify the level of health status. Each attribute or domain (eg, mobility, cognition, emotion or pain) is rated on a 5-point ordinal scale to indicate the severity level, ranging from 1-5 (higher numbers indicating a more severe level). | At 60 months CA | 
| Healthcare Resource Utilization | Healthcare resource utilization is measured by the number of in-patient and outpatient visits, including emergency room visits and visits to specialists. | 12 months CA through 60 months CA | 
| Number of Participants With Targeted Medical Events and Fatal Serious Adverse Events (SAEs) | Targeted medical events are intracranial hypertension, any abnormality of glucose metabolism (eg, hypoglycemia, hyperglycemia, and diabetes), tonsillar hypertrophy (based on tonsil examination [part of the physical examination]), and increased cardiac size. A serious adverse event (SAE) is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event. | 12 months CA through 60 months CA |