Safety, Pk and Anti-inflammatory Effects of CC10 Protein in Premature Infants With Respiratory Distress Syndrome (RDS)

Phase 1

Completed

• Conditions: Respiratory Distress Syndrome in Premature Infant; Bronchopulmonary Dysplasia
• Interventions: Drug: placebo; Drug: recombinant human CC10 (rhCC10)

• Registration Number: NCT01473264
• Lead Sponsor: Clarassance, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2000-01
• Primary Completion: 2002-06
• Study Completion: 2003-12
• Status Verified: 2011-11
• Study First Submitted: 2011-11-14
• Study First Submitted QC: 2011-11-16
• Last Update Submitted: 2011-11-16
• Study First Posted: 2011-11-17
• Last Update Posted: 2011-11-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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);

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	placebo	-
High dose rhCC10	recombinant human CC10 (rhCC10)	5 mg/kg study drug (rhCC10)
Low Dose rhCC10	recombinant human CC10 (rhCC10)	1.5 mg/kg study drug (rhCC10)

Primary Outcome Measures

Name	Time	Method
Number and type of adverse events	Adverse events were monitored through 36 wks post-menstrual age (PMA) or hospital discharge	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).

Secondary Outcome Measures

Name	Time	Method
Assessment of pulmonary inflammatory markers	Days 0-7	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	Through 36 wks postmenstrual age or discharge
Hospitalization at 36 weeks PMA	Through 36 wks postmenstrual age or discharge
Chronic Respiratory Morbidity	6 & 12 months postmenstrual age	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.

Trial Locations

Locations (4)

Winthrop-University Hospital, SUNY Stony Brook School of Medicine; 🇺🇸 Mineola, New York, United States

University of Maryland School of Medicine; 🇺🇸 Baltimore, Maryland, United States

Christiana HealthCare Systems; 🇺🇸 Wilmington, Delaware, United States

Mercy Medical Center; 🇺🇸 Baltimore, Maryland, United States