Low IGF-1 levels in extremely preterm infants (gestational age [GA] of 23 weeks +0 days to 27 weeks +6 days) are a risk factor for CLD and other complications of extreme prematurity. An increase of serum IGF-1 levels provided by SHP607 administration may reduce the incidence of CLD and other complications of extreme prematurity. This would be the only available preventive pharmacological therapy leading to an absolute decrease in the incidence of moderate or severe BPD and an absolute decrease in the incidence of IVH for extremely premature babies translating to an improvement in long-term pulmonary and neurodevelopmental outcomes which are key drivers for short- and long-term use of resources. Subjects will be randomly assigned on a per site basis to treatment either with SHP607 (250 μg/kg/24 hours or 400 μg/kg/24 hours) or to receive standard neonatal care in a 1:1:1 ratio. Standard neonatal care is determined based upon the individual premature infant’s condition and clinical judgment of the treating physician and may include interventions for thermoregulation, blood pressure support, respiratory/ventilatory support, nutritional support, treatment for infections, etc. Recognizing that medical care required for each premature infant may vary, other than those specific parameters outlined in the protocol, local neonatal intensive care unit (NICU) practices and investigator’s judgment for care decisions are to be followed. Subjects randomly assigned to treatment with SHP607 will receive continuous IV infusion of study drug commencing within 24 hours of birth, once all baseline assessments have been completed. The infusion of study drug will continue to PMA 29 weeks +6 days, when the subjects’ endogenous production of IGF-1 is considered sufficient to maintain physiologic serum IGF-1 levels for corresponding GA. Infusion of study drug may be discontinued before PMA 29 weeks +6 days if IV access is not possible according to the clinical judgment of the investigator or when the responsible physician, for other medical reasons, decides that infusion of study drug should be discontinued. Initially, enrollment will be restricted to subjects of GA ≥26 weeks (26 weeks +0 days to 27 weeks +6 days). After approximately 75 subjects (approximately 25 subjects in each treatment group) have completed the PMA 40 weeks visit, the DMC will assess safety and preliminary efficacy data, where preliminary efficacy assessments would include review of imbalances in BPD and IVH incidence between study groups. Based on the outcomes of these assessments, the DMC may authorize enrollment of subjects of GA between 23 weeks +0 days and 27 weeks +6
Takeda footprint
A Phase 2b, Multicenter, Randomized, Open-label, Controlled, 3-Arm Study to Evaluate the Clinical Efficacy and Safety of SHP607 in Preventing Chronic Lung Disease Through 12 Months Corrected Age Compared to Standard Neonatal Care in Extremely Premature Infants
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- Subjects must be between GA of 26 weeks +0 days and 27 weeks +6 days,
- Detectable major (or severe) congenital malformation identified before randomization.
- Known or suspected chromosomal abnormality, genetic disorder, or syndrome, identified before randomization, according to the investigator’s opinion.
- Hypoglycemia at Baseline (blood glucose <45 mg/dL or 2.5 mmol/L) which persists in spite of glucose supplementation, to exclude severe congenital abnormalities of glucose metabolism.
This is a Phase 2b, multicenter, randomized, open-label, controlled, 3-arm study to evaluate the clinical efficacy and safety of SHP607 in preventing CLD through 12 months CA compared to standard neonatal care in extremely premature infants.
Approximately 600 subjects will be randomized in a 1:1:1 ratio to receive either SHP607 at 250 μg/kg/24 hours, SHP607 at 400 μg/kg/24 hours, or standard neonatal care. Standard neonatal care is determined based upon the individual premature infant’s condition and clinical judgment of the treating physician and may include interventions for thermoregulation, blood pressure support, respiratory/ventilatory support, nutritional support, treatment for infections, etc. Recognizing that medical care required for each premature infant may vary, other than those specific parameters outlined in the protocol, local NICU practices and investigator’s judgment for care decisions are to be followed. Subjects randomly assigned to treatment with SHP607 will receive continuous IV infusion of investigational product commencing within 24 hours of birth, once all baseline assessments have been completed. The infusion of study drug will continue until PMA 29 weeks +6 days, when the subjects’ endogenous production of IGF-1 is considered sufficient to maintain physiologic serum IGF-1 levels for corresponding GA. Infusion of study drug may be discontinued before PMA 29 weeks +6 days if IV access is not possible according to the clinical judgment of the investigator or when the responsible physician, for other medical reasons, decides that infusion of study drug should be discontinued. Initially, enrollment will be restricted to subjects of GA ≥26 weeks (26 weeks +0 days to 27 weeks +6 days). After approximately 75 subjects (approximately 25 subjects in each treatment group) have completed the PMA 40 weeks visit, the DMC will assess safety and preliminary efficacy data, where preliminary efficacy assessments would include review of imbalances in BPD and IVH incidence between study groups. Based on the outcomes of these assessments, the DMC may authorize enrollment of subjects of GA between 23 weeks +0 days and 27 weeks +6 days, or may recommend enrollment of additional subjects of GA ≥26 weeks, suspension of enrollment, or discontinuation of the study. For subsequent subjects who are enrolled, randomization will be stratified by GA at birth (either <25 weeks [23 weeks +0 daysthrough 24 weeks +6 days], 25 weeks [25 weeks +0 days through 25 weeks +6 days], or ≥26 weeks [26 weeks +0 days to 27 weeks +6 days]) within each site. CLD will be assessed by analyzing the time to final weaning off RTS from Day 1 through 12 months CA. RTS is defined as any of the following: (1) any fraction of inspired oxygen (FiO2) >21%, (2) non-invasive respiratory support delivered via a nasal interface (eg, continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP], high flow therapy, nasal intermittent positive pressure ventilation [NIPPV], nasal cannula), (3) invasive respiratory support (mechanical ventilation) via an endotracheal tube or tracheostomy. During the birth hospitalization, RTS will be recorded daily by site personnel. After NICU discharge, daily RTS usage will be recorded weekly by parent(s)/caregiver(s), via an electronic device. RTS will also be captured during inpatient re-hospitalizations. Assessment of BPD by modified NICHD severity grading, confirmation of BPD by oxygen challenge testing, cranial ultrasounds, measurement of growth parameters, and ROP examinations will be performed Chronic respiratory morbidity will be assessed from NICU discharge to 12 months CA, using data collected weekly by parent(s) or legally authorized representative(s) via an electronic device Blood samples will be collected to monitor hyperglycemia, and to measure serum IGF-1, IGFBP-3, exploratory biomarkers, IgG/IgM antibodies, and laboratory values at the time points specified in the Schedules of Assessments Motor function will be ssessed by the AIMS. Functional status will be measured using PREMII ClinRO assessments. HRQoL will be assessed using the PedsQL™ infant scales and caregiver health status will be assessed using EQ-5D-5L. AEs will be assessed, and laboratory values and vital signs will be obtained to evaluate the safety and tolerability of SHP607. An independent DMC will provide periodic, independent review and assessment of safety data, to safeguard the interests and safety of the subjects participating in the study.