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

NCT01473264 | Completed Phase 1 DMC

• 2 other identifiers: CC10-2000-0019R44HL066965-02
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Assessment of pulmonary inflammatory markers

  Days 0-7

• 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

Study Arms (3)

Control

PLACEBO COMPARATOR

Drug: placebo

High dose rhCC10

EXPERIMENTAL

5 mg/kg study drug (rhCC10)

Drug: recombinant human CC10 (rhCC10)

Low Dose rhCC10

EXPERIMENTAL

1.5 mg/kg study drug (rhCC10)

Drug: recombinant human CC10 (rhCC10)

Interventions

recombinant human CC10 (rhCC10) 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.

Also known as: rhCC10, CC10, uteroglobin, Clara cell secretory protein, Clara cell 10 kDa protein

High dose rhCC10

placebo 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.

Control

Eligibility Criteria

• Age: 24 Weeks - 29 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• Major congenital abnormalities (chromosomal, genetic, cardiac, pulmonary, or renal);

Sponsors & Collaborators

• Clarassance, Inc.: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (4)

Christiana HealthCare Systems

Wilmington, Delaware, 19899, United States

Location

University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Winthrop-University Hospital, SUNY Stony Brook School of Medicine

Mineola, New York, 11501, United States

Location

Related 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 syndrome. Pediatr Res. 2005 Jul;58(1):15-21. doi: 10.1203/01.PDR.0000156371.89952.35. Epub 2005 Mar 17.

  PMID: 15774846 RESULT

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Premature Birth; Pneumonia

Interventions

Uteroglobin

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Respiratory Tract Infections; Infections

Intervention Hierarchy (Ancestors)

Secretoglobins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Jonathan M Davis, MD

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

  PRINCIPAL INVESTIGATOR

• Ira Gewolb, M.D.

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2011
• First Posted: November 17, 2011
• Study Start: January 1, 2000
• Primary Completion: June 1, 2002
• Study Completion: December 1, 2003
• Last Updated: November 17, 2011

Record last verified: 2011-11

Locations

US (4)