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

Bronchopulmonary Dysplasia Clinical Trial

Official title:

Safety and Tolerability of Recombinant Human Clara Cell 10kDa Protein (rhCC10) Delivered Intratracheally to Premature Neonates With Respiratory Distress Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01473264
• Other study ID #: CC10-2000-001
• Secondary ID: 9R44HL066965-02
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 14, 2011
• Last updated: November 16, 2011
• Start date: January 2000
• Est. completion date: December 2003

Study information

• Verified date: November 2011
• Source: Clarassance, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: NIH, National Heart, Lung, and Blood Institute (NHLBI)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: December 2003
• Est. primary completion date: June 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 24 Weeks to 29 Weeks

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Premature Birth
• Respiratory Distress Syndrome in Premature Infant
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

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.
• 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
• 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.

Locations

Country	Name	City	State
United States	Mercy Medical Center	Baltimore	Maryland
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	Winthrop-University Hospital, SUNY Stony Brook School of Medicine	Mineola	New York
United States	Christiana HealthCare Systems	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
Clarassance, Inc.	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 s — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and type of adverse events	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).	Adverse events were monitored through 36 wks post-menstrual age (PMA) or hospital discharge	Yes
Secondary	Assessment of pulmonary inflammatory markers	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	Days 0-7	No
Secondary	Total number of days on mechanical ventilation		Through 36 wks postmenstrual age or discharge	No
Secondary	Hospitalization at 36 weeks PMA		Through 36 wks postmenstrual age or discharge	No
Secondary	Chronic Respiratory Morbidity	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.	6 & 12 months postmenstrual age	No