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

Clarassance

Status and phase: Completed; Phase 2; Phase 1

Conditions: Respiratory Distress Syndrome in Premature Infant; Bronchopulmonary Dysplasia

Treatments: Drug: placebo; Drug: recombinant human CC10 (rhCC10)

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT01473264

9R44HL066965-02 (U.S. NIH Grant/Contract)

CC10-2000-001

Details and patient eligibility

About

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.

Enrollment: 22 patients

Sex: All

Ages: 24 to 29 weeks old

Volunteers: No Healthy Volunteers

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);

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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22 participants in 3 patient groups, including a placebo group

Control

Placebo Comparator group

Treatment:

Drug: placebo

High dose rhCC10

Experimental group

Description:

5 mg/kg study drug (rhCC10)

Treatment:

Drug: recombinant human CC10 (rhCC10)

Drug: recombinant human CC10 (rhCC10)

Low Dose rhCC10

Experimental group

Description:

1.5 mg/kg study drug (rhCC10)

Treatment:

Drug: recombinant human CC10 (rhCC10)

Drug: recombinant human CC10 (rhCC10)