Efficacy of Recombinant Human Clara Cell 10 Protein (rhCC10) Administered to Premature Neonates With Respiratory Distress Syndrome
Condition: Respiratory Distress Syndrome in Premature Infant; Bronchopulmonary Dysplasia
MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Bronchopulmonary Dysplasia; Premature Birth; Syndrome
Intervention: Half normal saline; Low Dose rhCC10; High dose rhCC10
Intervention description: 2 ml/kg; 1.5 mg/kg study drug (rhCC10); 5 mg/kg in 2 ml/kg
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 88.0
Sex: All
Minimum age: 24 Weeks
Maximum age: 29 Weeks
Healthy volunteers: No

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 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).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age less than or equal to 24 hours;

          -  Birth weight 600 - 1250 grams;

          -  Gestational age 24-29 weeks (not less than 24 weeks); at birth based on best estimate
             using obstetrical sonography (first or second trimester), solid dating criteria, or
             Ballard examination;

          -  Birth weight appropriate for gestational age;

          -  5 minute Apgar score >5;

          -  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 (prophylaxis or rescue); and

          -  Written informed consent is obtained from at least one of the infant's parents or
             legal guardians (see section 6.2) prior to enrollment of the subject. The parent(s) or
             legal guardian(s) must agree to all study-related procedures and evaluations.

        Exclusion Criteria:

          -  5 minute Apgar score of ≤ 5;

          -  Major congenital anomaly (chromosomal, renal, cardiac, hepatic, neurologic, or
             pulmonary malformations; minor anomalies such as cleft lip/palate are permitted);

          -  Evidence of severe neonatal depression (as defined by cord blood acid-base balance
             (pH) ≤ 7.00 and/or an Apgar score of < 4 at 10 minutes);

          -  Evidence of congenital infection;

          -  Requires a major surgical procedure prior to administration of Study drug

          -  Enrollment in any other study involving administration of another investigational
             drug;

          -  Any condition which could preclude receiving study drug or performing any
             study-related procedures;

          -  Use of postnatal corticosteroids prior to administration of r-hCC10, except as
             specified in the protocol;

          -  Use of inhaled nitric oxide prior to administration of r-hCC10;

          -  Mother is known to be seropositive for HIV (per maternal medical records);

          -  Parent or guardian is unable or unwilling to complete the study diary;

          -  Parent or guardian is unable to bring the infant back to the study center for
             follow-up evaluations.