Safety, Pk and Anti-inflammatory Effects of CC10 Protein in Premature Infants With Respiratory Distress Syndrome (RDS)
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Purpose
Bronchopulmonary Dysplasia (BPD) is a multi-factorial disease process that is the end result of an immature, surfactant deficient lung that has been exposed to hyperoxia, mechanical ventilation and infection. These conditions initiate an inflammatory response characterized by elevated inflammatory cell infiltrates and proinflammatory cytokines that lead to the development of significant acute and chronic lung injury.
The study drug, rhCC10, is a recombinant version of natural human CC10 protein. Native CC10 is produced primarily by non-ciliated respiratory epithelial cells, called Clara cells and is the most abundant protein in the mucosal fluids in normal healthy lungs.
The purpose of this study was to evaluate the pharmacokinetics, safety, tolerability and anti-inflammatory effects of a single intratracheal (IT) dose of rhCC10 to intubated premature infants receiving positive pressure ventilation for treatment of respiratory distress syndrome (RDS) to prevent long term respiratory complications referred to as bronchopulmonary dysplasia, and, more recently, as chronic respiratory morbidity (CRM; asthma, cough, wheezing, multiple respiratory infections).
CC10 regulates inflammatory responses and protects the structural integrity of pulmonary tissue while preserving pulmonary mechanical function during various insults (eg. viral infection, bacterial endotoxin, ozone, allergens, hyperoxia). Together these properties suggest that administration of rhCC10 may help to facilitate development of normal airway epithelia and prevent the inflammation that leads to CRM in these infants.
| Condition | Intervention | Phase |
|---|---|---|
|
Respiratory Distress Syndrome in Premature Infant Bronchopulmonary Dysplasia |
Drug: recombinant human CC10 (rhCC10) Drug: placebo |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Prevention |
| Official Title: | Safety and Tolerability of Recombinant Human Clara Cell 10kDa Protein (rhCC10) Delivered Intratracheally to Premature Neonates With Respiratory Distress Syndrome |
- Number and type of adverse events [ Time Frame: Adverse events were monitored through 36 wks post-menstrual age (PMA) or hospital discharge ] [ Designated as safety issue: Yes ]All adverse events were monitored according to the NCI Common Toxicity Criteria. In addition, adverse events specific to, or likely to occur in, premature infants were also monitored, including apnea/bradycardia, sepsis (culture-confirmed), patent ductus arteriosus, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, and necrotizing enterocolitis (NEC).
- Assessment of pulmonary inflammatory markers [ Time Frame: Days 0-7 ] [ Designated as safety issue: No ]Total cell and neutophil counts were performed on TAF fluids. In addition, a panel of cytokines were measured in TAF from patients at times 0, 1, and 2 days
- Total number of days on mechanical ventilation [ Time Frame: Through 36 wks postmenstrual age or discharge ] [ Designated as safety issue: No ]
- Hospitalization at 36 weeks PMA [ Time Frame: Through 36 wks postmenstrual age or discharge ] [ Designated as safety issue: No ]
- Chronic Respiratory Morbidity [ Time Frame: 6 & 12 months postmenstrual age ] [ Designated as safety issue: No ]Physical exams and Bayley neurological exams were performed at 12 months PMA. Data pertaining to respiratory outcomes were collected at 6 and 12 months PMA.
| Enrollment: | 22 |
| Study Start Date: | January 2000 |
| Study Completion Date: | December 2003 |
| Primary Completion Date: | June 2002 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Placebo Comparator: Control |
Drug: placebo
Half normal saline solution; single dose delivered intratracheally (IT). Treatment was delivered within four hours after surfactant treatment. Dose was delivered IT in two (2) equal aliquots via a premeasured feeding tube placed in the distal third of the endotracheal tube with the patient in the right and then left lateral decubitus position and 30 degrees of Trendelenburg.
|
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Experimental: High dose rhCC10
5 mg/kg study drug (rhCC10)
|
Drug: recombinant human CC10 (rhCC10)
5 mg/kg rhCC10, single dose delivered intratracheally (IT). Treatment was delivered within four hours after surfactant treatment. Dose was delivered IT in two (2) equal aliquots via a premeasured feeding tube placed in the distal third of the endotracheal tube with the patient in the right and then left lateral decubitus position and 30 degrees of Trendelenburg.
Other Names:
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Experimental: Low Dose rhCC10
1.5 mg/kg study drug (rhCC10)
|
Drug: recombinant human CC10 (rhCC10)
1.5 mg/kg rhCC10, single dose delivered intratracheally (IT). Treatment was delivered within four hours after surfactant treatment. Dose was delivered IT in two (2) equal aliquots via a premeasured feeding tube placed in the distal third of the endotracheal tube with the patient in the right and then left lateral decubitus position and 30 degrees of Trendelenburg
Other Names:
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Eligibility| Ages Eligible for Study: | 24 Weeks to 29 Weeks |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Newborn infants were considered for the study if the following criteria were met:
- Age < 24 hours;
- Birthweight between 700 and 1,300 grams;
- Gestational age greater than or equal to 24 weeks;
- Diagnosis of neonatal RDS based on clinical and radiographic criteria;
- Requiring intubation and mechanical ventilation for treatment of RDS;
- Received at least one dose of surfactant 100 mg/kg (Survanta; Ross Laboratories);
- Written informed consent from the infant's parent or legal guardian prior to enrollment of the patient and agrees to all study-related procedures and evaluations, including those required after hospital discharge.
Exclusion Criteria:
• Major congenital abnormalities (chromosomal, genetic, cardiac, pulmonary, or renal);
Contacts and Locations| United States, Delaware | |
| Christiana HealthCare Systems | |
| Wilmington, Delaware, United States, 19899 | |
| United States, Maryland | |
| University of Maryland School of Medicine | |
| Baltimore, Maryland, United States, 21201 | |
| Mercy Medical Center | |
| Baltimore, Maryland, United States, 21202 | |
| United States, New York | |
| Winthrop-University Hospital, SUNY Stony Brook School of Medicine | |
| Mineola, New York, United States, 11501 | |
| Principal Investigator: | Jonathan M Davis, MD | Dept of pediatrics, Winthrop University Hospital, SUNY Stony Brook School of Medicine |
| Principal Investigator: | Ira Gewolb, M.D. | University of Maryland |
More Information
Publications:
| Responsible Party: | Clarassance, Inc. |
| ClinicalTrials.gov Identifier: | NCT01473264 History of Changes |
| Other Study ID Numbers: | CC10-2000-001, 9R44HL066965-02 |
| Study First Received: | November 14, 2011 |
| Last Updated: | November 16, 2011 |
| Health Authority: | United States: Food and Drug Administration United States: NIH, National Heart, Lung, and Blood Institute (NHLBI) |
Keywords provided by Clarassance, Inc.:
|
CC10 BPD Bronchopulmonary dysplasia premature infants |
neonates pulmonary inflammation lung function RDS |
Additional relevant MeSH terms:
|
Bronchopulmonary Dysplasia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Ventilator-Induced Lung Injury Lung Injury |
Lung Diseases Respiratory Tract Diseases Infant, Premature, Diseases Infant, Newborn, Diseases Respiration Disorders |
ClinicalTrials.gov processed this record on June 18, 2013