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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Clarassance, Inc.
ClinicalTrials.gov Identifier:
NCT01473264
First received: November 14, 2011
Last updated: November 16, 2011
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Respiratory Distress Syndrome in Premature Infant
Bronchopulmonary Dysplasia
Drug: recombinant human CC10 (rhCC10)
Drug: placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Safety and Tolerability of Recombinant Human Clara Cell 10kDa Protein (rhCC10) Delivered Intratracheally to Premature Neonates With Respiratory Distress Syndrome

Resource links provided by NLM:


Further study details as provided by Clarassance, Inc.:

Primary Outcome Measures:
  • Number and type of adverse events [ Time Frame: Adverse events were monitored through 36 wks post-menstrual age (PMA) or hospital discharge ] [ Designated as safety issue: Yes ]
    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:
  • Assessment of pulmonary inflammatory markers [ Time Frame: Days 0-7 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Through 36 wks postmenstrual age or discharge ] [ Designated as safety issue: No ]
  • Hospitalization at 36 weeks PMA [ Time Frame: Through 36 wks postmenstrual age or discharge ] [ Designated as safety issue: No ]
  • Chronic Respiratory Morbidity [ Time Frame: 6 & 12 months postmenstrual age ] [ Designated as safety issue: No ]
    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.


Enrollment: 22
Study Start Date: January 2000
Study Completion Date: December 2003
Primary Completion Date: June 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Control 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.
Experimental: High dose rhCC10
5 mg/kg study drug (rhCC10)
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.
Other Names:
  • rhCC10
  • CC10
  • uteroglobin
  • Clara cell secretory protein
  • Clara cell 10 kDa protein
Experimental: Low Dose rhCC10
1.5 mg/kg study drug (rhCC10)
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
Other Names:
  • rhCC10
  • CC10
  • uteroglobin
  • Clara cell secretory protein
  • Clara cell 10 kDa protein

  Eligibility

Ages Eligible for Study:   24 Weeks to 29 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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);

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01473264

Locations
United States, Delaware
Christiana HealthCare Systems
Wilmington, Delaware, United States, 19899
United States, Maryland
University of Maryland School of Medicine
Baltimore, Maryland, United States, 21201
Mercy Medical Center
Baltimore, Maryland, United States, 21202
United States, New York
Winthrop-University Hospital, SUNY Stony Brook School of Medicine
Mineola, New York, United States, 11501
Sponsors and Collaborators
Clarassance, Inc.
Investigators
Principal Investigator: 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
  More Information

Publications:
Responsible Party: Clarassance, Inc.
ClinicalTrials.gov Identifier: NCT01473264     History of Changes
Other Study ID Numbers: CC10-2000-001, 9R44HL066965-02
Study First Received: November 14, 2011
Last Updated: November 16, 2011
Health Authority: United States: Food and Drug Administration
United States: NIH, National Heart, Lung, and Blood Institute (NHLBI)

Keywords provided by Clarassance, Inc.:
CC10
BPD
Bronchopulmonary dysplasia
premature infants
neonates
pulmonary inflammation
lung function
RDS

Additional relevant MeSH terms:
Bronchopulmonary Dysplasia
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Ventilator-Induced Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Respiration Disorders

ClinicalTrials.gov processed this record on July 29, 2014