Efficacy of Recombinant Human Clara Cell 10 Protein (rhCC10) Administered to Premature Neonates With Respiratory Distress Syndrome
|ClinicalTrials.gov Identifier: NCT01941745|
Recruitment Status : Completed
First Posted : September 13, 2013
Results First Posted : September 10, 2019
Last Update Posted : September 10, 2019
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 Pulmonary Insufficiency of Prematurity (CPIP; 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 CPIP 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)|
|Actual 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|
|Actual Study Start Date :||October 2013|
|Actual Primary Completion Date :||August 25, 2017|
|Actual Study Completion Date :||August 25, 2017|
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 Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 12 Months Corrected Gestational Age (CGA) [ Time Frame: 12 Months Corrected Gestational Age (*no imputation for missing data) ]
Number of events of survived participants without one or more of the CPIP components defined below:
- Medical/ER visits (CPIP-DV): At least one non-routine medical visit for respiratory causes.
- Respiratory re-hospitalizations (CPIP-RH): One or more re-hospitalizations for respiratory causes.
- Respiratory Symptoms (CPIP-SS): Evidence of respiratory symptoms (e.g. coughing and wheezing) or use of respiratory medications by parental diaries or pulmonary questionnaires.
- Respiratory Medications (CPIP-RM): Administration of respiratory medications (including oxygen).
CPIP is defined as the presence of one or more parent-reported outcomes at 12 months CGA, validated by Respiratory diaries (presence of wheezing, coughing, and/or respiratory medication use ≥2 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).
- Long Term Efficacy - Survival Without Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 6 Months Corrected Gestational Age (CGA) [ Time Frame: 6 months Corrected Gestational Age ]
Number of events of survived participants, graded as not having 1, 2, 3, or 4 of the CPIP components defined below:
Medical/ER visits (CPIP-DV): ≥1 non-routine medical visit(s) for respiratory causes.
Respiratory re-hospitalizations (CPIP-RH): ≥1 re-hospitalization(s) for respiratory causes Respiratory Symptoms (CPIP-SS): Parent-reported evidence of respiratory symptoms (e.g. coughing and wheezing) or use of respiratory medications Respiratory Medications (CPIP-RM): Administration of respiratory medications (including oxygen)
A participant graded without 4 CPIP components is considered in better health than a participant graded without 1 CPIP component. CPIP components were parent-validated via respiratory diaries (wheezing, coughing, and/or respiratory medication use ≥2 days/wk for 3 consecutive wks), and pulmonary questionnaires (decrease in respiratory illness requiring medications, unscheduled medical visits and/or ER or hospital admissions).
- Safety and Efficacy - Number of Participants With Adverse Events [ Time Frame: Adverse events are monitored through 36 wks post-menstrual age (PMA) ]The safety of the study drug was assessed by accounting the number of participants with Adverse Events (AEs) in the treatment and placebo groups.
- Short Term Efficacy - Number of Neonates With Oxygen Requirement at 36 Weeks Post Menstrual Age [ Time Frame: 36 weeks post-menstrual age ]Short term efficacy evaluations involve number of neonates with oxygen requirement at 36 weeks post menstrual age.
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|