Clinical trial NCT01473264: Safety, Pk and Anti-inflammatory Effects of CC10 Protein in Premature Infants With Respiratory Distress Syndrome (RDS)
Official title: Safety and Tolerability of Recombinant Human Clara Cell 10kDa Protein (rhCC10) Delivered Intratracheally to Premature Neonates With Respiratory Distress Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Respiratory Distress Syndrome in Premature Infant
Bronchopulmonary Dysplasia
Keywords: CC10
BPD
Bronchopulmonary dysplasia
premature infants
neonates
pulmonary inflammation
lung function
RDS
Lead sponsor: Clarassance, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2011-11-17
Enrollment: 22
Sex: ALL
Minimum age (years): 24
Maximum age (years): 29
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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);

Primary outcomes:
measure: Number and type of adverse events
timeFrame: Adverse events were monitored through 36 wks post-menstrual age (PMA) or hospital discharge
Secondary outcomes:
measure: Assessment of pulmonary inflammatory markers
timeFrame: Days 0-7
measure: Total number of days on mechanical ventilation
timeFrame: Through 36 wks postmenstrual age or discharge
measure: Hospitalization at 36 weeks PMA
timeFrame: Through 36 wks postmenstrual age or discharge
measure: Chronic Respiratory Morbidity
timeFrame: 6 & 12 months postmenstrual age
Other outcomes:
Locations:
city: Wilmington
country: United States
facility: Christiana HealthCare Systems
state: Delaware
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Mineola
country: United States
facility: Winthrop-University Hospital, SUNY Stony Brook School of Medicine
state: New York
Study officials:
affiliation: Dept of pediatrics, Winthrop University Hospital, SUNY Stony Brook School of Medicine
name: Jonathan M Davis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Maryland, Baltimore
name: Ira Gewolb, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Levine CR, Gewolb IH, Allen K, Welch RW, Melby JM, Pollack S, Shaffer T, Pilon AL, Davis JM. The safety, pharmacokinetics, and anti-inflammatory effects of intratracheal recombinant human Clara cell protein in premature infants with respiratory distress syndrome. Pediatr Res. 2005 Jul;58(1):15-21. doi: 10.1203/01.PDR.0000156371.89952.35. Epub 2005 Mar 17.