Efficacy of Recombinant Human Clara Cell 10 Protein (rhCC10) Administered to Premature Neonates With Respiratory Distress Syndrome
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01941745|
Recruitment Status : Active, not recruiting
First Posted : September 13, 2013
Last Update Posted : October 12, 2017
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 is 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.
This study is funded by the FDA Office of Orphan Product Development (OOPD).
|Condition or disease||Intervention/treatment||Phase|
|Respiratory Distress Syndrome in Premature Infant Bronchopulmonary Dysplasia||Drug: Half normal saline Drug: Low Dose rhCC10 Drug: High dose rhCC10||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||88 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Efficacy of Recombinant Human Clara Cell Protein (rhCC10) Administered to Premature Neonates With Respiratory Distress Syndrome|
|Study Start Date :||October 2013|
|Estimated Primary Completion Date :||February 2018|
|Estimated Study Completion Date :||August 2018|
Placebo Comparator: half normal saline
Single dose of half normal saline at 2 ml/kg given intratracheally times one dose
Drug: Half normal saline
Experimental: Low Dose rhCC10
1.5 mg/kg study drug (rhCC10)in 2 ml/kg given intratracheally times one dose
Drug: Low Dose rhCC10
1.5 mg/kg study drug (rhCC10)
Experimental: High dose rhCC10
5 mg/kg of rhCC10 given in 2 ml/kg and administered intratracheally times one dose
Drug: High dose rhCC10
5 mg/kg in 2 ml/kg
- Survival without chronic respiratory morbidity (CRM) at 12 months corrected gestational age [ Time Frame: 12 Months Corrected Gestational Age ]The primary outcome of the study will be survival without chronic respiratory morbidity (CRM) through 12 months corrected gestational age (CGA) as measured by validated respiratory diaries (presence of wheezing, coughing, and/or respiratory medication use 2 or more days per week for 3 consecutive weeks) and pulmonary questionnaires (decrease in respiratory illness requiring medications, unscheduled medical visits and/or ER or hospital admissions) which have been shown to correlate more closely with abnormalities on pulmonary function testing. The 12 month CGA endpoint has been shown to be more predictive of respiratory morbidity than a diagnosis of BPD at 36 weeks post-menstrual in previous studies of recombinant human superoxide dismutase and high frequency oscillatory ventilation in preterm infants conducted by the clinical investigator's research groups.
- Long Term Efficacy [ Time Frame: 6 months corrected gestational age ]A secondary outcome of the study will be survival without CRM at 6 months CGA as measured by validated respiratory diaries (presence of wheezing, coughing, or respiratory medication use 2 or more days per week for 3 consecutive weeks) and pulmonary questionnaires (decrease in respiratory illness requiring medications and/or hospitalization) which have been shown to correlate closely with abnormalities on pulmonary function testing. Infants will be also be evaluated at 18 months CGA to evaluate growth and neurological development.
- Safety and Efficacy - Adverse Events [ Time Frame: Adverse events are monitored through 36 wks post-menstrual age (PMA) ]The safety of the study drug will continue to be assessed by comparing the incidence of adverse events and serious adverse events in the treatment and placebo groups as well as the historical incidence of the adverse events at each institution.
- Short term Efficacy [ Time Frame: 36 weeks post-menstrual age ]Short term efficacy evaluations will include time on mechanical ventilation, oxygen requirement at 36 weeks post menstrual age, and survival without BPD at 36 weeks post-menstrual age as measured by oxygen challenge testing.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01941745
|United States, Massachusetts|
|Tufts Medical Center|
|Boston, Massachusetts, United States, 02111|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Baystate Medical Center|
|Springfield, Massachusetts, United States, 01199|
|Principal Investigator:||Jonathan Davis, MD||Tufts Medical Center|
|Principal Investigator:||Richard Parad, MD/MPH||Brigham and Women's Hospital|