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

NCT ID: NCT01473264

Last Updated: 2011-11-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-01-31
• Study Completion Date: 2003-12-31

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.

Conditions

Respiratory Distress Syndrome in Premature Infant; Bronchopulmonary Dysplasia

Keywords

CC10; BPD; Bronchopulmonary dysplasia; premature infants; neonates; pulmonary inflammation; lung function; RDS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Control

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

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.

High dose rhCC10

5 mg/kg study drug (rhCC10)

Group Type: EXPERIMENTAL

recombinant human CC10 (rhCC10)

Intervention Type: DRUG

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.

Low Dose rhCC10

1.5 mg/kg study drug (rhCC10)

Group Type: EXPERIMENTAL

recombinant human CC10 (rhCC10)

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

rhCC10; CC10; uteroglobin; Clara cell secretory protein; Clara cell 10 kDa protein; rhCC10; CC10; uteroglobin; Clara cell secretory protein; Clara cell 10 kDa protein

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);

• Minimum Eligible Age: 24 Weeks
• Maximum Eligible Age: 29 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Clarassance, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan M Davis, MD

Role: PRINCIPAL_INVESTIGATOR

Dept of pediatrics, Winthrop University Hospital, SUNY Stony Brook School of Medicine

Ira Gewolb, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Locations

Christiana HealthCare Systems

Wilmington, Delaware, United States

University of Maryland School of Medicine

Baltimore, Maryland, United States

Mercy Medical Center

Baltimore, Maryland, United States

Winthrop-University Hospital, SUNY Stony Brook School of Medicine

Mineola, New York, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 15774846 (View on PubMed)

Other Identifiers

9R44HL066965-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CC10-2000-001

Identifier Type: -

Identifier Source: org_study_id