Retinopathy of Prematurity (ROP) Clinical Trial
Official title:
Determination of the rhIGF-1/rhIGFBP-3 Dose, Administered as a Continuous Infusion, Required to Establish and Maintain Longitudinal Serum IGF-1 Levels Within Physiological Levels in Premature Infants, to Prevent Retinopathy of Prematurity A Phase 2, Randomized Controlled, Assessor-blind, Dose Confirming, Pharmacokinetic, Safety and Efficacy, Multicenter Study
Verified date | May 2021 |
Source | Takeda |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 121 |
Est. completion date | March 30, 2016 |
Est. primary completion date | March 30, 2016 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A to 1 Day |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Italy | D.A.I. Materno Infantile, S.O.D. Neonatologia e Terapia Intensiva Neonatale - Azienda Ospedaliero-Universitaria Careggi | Firenze | |
Italy | U.O.C Patologia e Terapia Intensiva Neonatale, Istituto Giannina Gaslini-Istituto Pediatrico di Ricovero e Cura a Carattere Scientifico | Genova | |
Italy | University of Padua | Padua | |
Italy | Dipartimento per la Tutella della Salute della Donna e della Vita Nascente, del Bambino e dell'Adolescente-U.O.C. Neonatologia-Poli. Gemelli | Rome | |
Netherlands | VU medical Center | Amsterdam | |
Poland | Instytut Centrum Zdrowia Matki Polki | Lódz | |
Poland | Ginekologiczno-Polozniczy Szpital Kliniczny Uniwersytetu Medycznego w Poznani | Poznan | |
Sweden | Skånes University Hospital Lund | Lund | |
Sweden | Karolinska Universtitetssjukhuset i Huddinge | Stockholm | |
United Kingdom | Addenbrookes Hospital | Cambridge | |
United Kingdom | St Peter's Hospital; Ashford & S | Chertsey | |
United Kingdom | University Hospital | Coventry | |
United Kingdom | Alder Hey Children's NHS Foundation Trust | Liverpool | |
United Kingdom | UCL EGA Institute for Women's Health | London | |
United Kingdom | St. Mary's Hospital | Manchester | |
United Kingdom | Norfolk and Norwich University | Norwich | |
United States | Georgia Regents Medical Center | Augusta | Georgia |
United States | Vidant Medical Center | Greenville | North Carolina |
United States | Univ of California Irvine Med Center | Irvine | California |
United States | Univ of Mississippi Medical Center | Jackson | Mississippi |
United States | University of Wisconsin - Madison | Madison | Wisconsin |
United States | University of South Alabama Children's and Women's Hospital | Mobile | Alabama |
United States | West Virginia University Hospital | Morgantown | West Virginia |
United States | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma |
Lead Sponsor | Collaborator |
---|---|
Shire |
United States, Italy, Netherlands, Poland, Sweden, United Kingdom,
Ley D, Hansen-Pupp I, Niklasson A, Domellöf M, Friberg LE, Borg J, Löfqvist C, Hellgren G, Smith LE, Hård AL, Hellström A. Longitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants: pharmacokineti — View Citation
Löfqvist C, Niklasson A, Engström E, Friberg LE, Camacho-Hübner C, Ley D, Borg J, Smith LE, Hellström A. A pharmacokinetic and dosing study of intravenous insulin-like growth factor-I and IGF-binding protein-3 complex to preterm infants. Pediatr Res. 2009 May;65(5):574-9. doi: 10.1203/PDR.0b013e31819d9e8c. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
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). | End of study | |
Secondary | Time to Discharge From Neonatal Intensive Care (TDNIC) | Day 0 to 40 Weeks Post Menstrual Age (EOS) | ||
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. | At 36 Weeks Post Menstrual Age | |
Secondary | Rate of Change in Body Weight | The rate of change is the rate of specific body weight change per day in kilogram (kg). | Day 0 to 40 Weeks Post Menstrual Age (EOS) | |
Secondary | Rate of Change in Length | The rate of change is the length change per day in centimeter (cm). | Day 0 to 40 Weeks Post Menstrual Age (EOS) | |
Secondary | Rate of Change in Head Circumference | The rate of change is the head circumference change per day in centimetre (cm). | Day 0 to 40 Weeks Post Menstrual Age (EOS) | |
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 | 40 Weeks PMA/ (EOS) +/- 4 days | |
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). | Day 0 to 40 Weeks Post Menstrual Age (EOS) | |
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. | Every 1-2 weeks starting at 31 weeks PMA/ EOS +/- 4 days | |
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. | Day 0 to 40 Weeks Post Menstrual Age (EOS) | |
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. | Day 0 to 40 Weeks Post Menstrual Age (EOS) | |
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. | Day 0 to 40 Weeks Post Menstrual Age (EOS) | |
Secondary | Serum Concentrations of IGFBP-3 After Intravenous (IV) Infusion of rhIGF-1/rhIGFBP-3 | Day 0 and Week 40 Post Menstrual Age | ||
Secondary | 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 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT04506619 -
Safety and Efficacy Outcomes Following Previously Administered Short-Term Treatment With SHP607 in Extremely Premature Infants
|
||
Completed |
NCT04004208 -
Aflibercept for Retinopathy of Prematurity - Intravitreal Injection Versus Laser Therapy
|
Phase 3 | |
Recruiting |
NCT03253263 -
A Clinical Efficacy and Safety Study of OHB-607 in Preventing Bronchopulmonary Dysplasia in Extremely Premature Infants
|
Phase 2 | |
Completed |
NCT02386839 -
Long-term Safety and Efficacy Outcome Study Comparing Children Previously Enrolled in Study ROPP-2008-01 for the Prevention of Retinopathy of Prematurity (ROP)
|
Phase 2 | |
Withdrawn |
NCT01470430 -
VEGF In Systemic Circulation Of ROP-infants
|
N/A | |
Completed |
NCT01054027 -
Study on Effective Mydriasis in Premature Infants
|
N/A | |
Active, not recruiting |
NCT04015180 -
Extension Study to Evaluate the Long-term Outcomes of Subjects in Study 20090
|
Phase 3 | |
Completed |
NCT02640664 -
Rainbow Extension Study
|
Phase 3 | |
Completed |
NCT02134457 -
Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity
|
Phase 2 | |
Terminated |
NCT01954082 -
Inositol to Reduce Retinopathy of Prematurity
|
Phase 3 |