Efficacy of Recombinant Human Clara Cell 10 Protein (rhCC10) Administered to Premature Neonates With Respiratory Distress Syndrome

NCT01941745 | Completed Phase 2 Results DMC

• 2 other identifiers: rhCC10 Study 2013Grant #3899
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 3

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 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).

Conditions

Respiratory Distress Syndrome in Premature Infant; Bronchopulmonary Dysplasia

Outcome Measures

Primary Outcomes (1)

• Survival Without Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 12 Months Corrected Gestational Age (CGA)

  Number of events of survived participants without one or more of the CPIP components defined below: 1. Medical/ER visits (CPIP-DV): At least one non-routine medical visit for respiratory causes. 2. Respiratory re-hospitalizations (CPIP-RH): One or more re-hospitalizations for respiratory causes. 3. Respiratory Symptoms (CPIP-SS): Evidence of respiratory symptoms (e.g. coughing and wheezing) or use of respiratory medications by parental diaries or pulmonary questionnaires. 4. 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).

  12 Months Corrected Gestational Age (*no imputation for missing data)

Secondary Outcomes (3)

• Long Term Efficacy - Survival Without Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 6 Months Corrected Gestational Age (CGA)

  6 months Corrected Gestational Age

• Safety and Efficacy - Number of Participants With Adverse Events

  Adverse events are monitored through 36 wks post-menstrual age (PMA)

• Short Term Efficacy - Number of Neonates With Oxygen Requirement at 36 Weeks Post Menstrual Age

  36 weeks post-menstrual age

Study Arms (3)

half normal saline

PLACEBO COMPARATOR

Single dose of half normal saline at 2 ml/kg given intratracheally times one dose

Drug: Half normal saline

Low Dose rhCC10

EXPERIMENTAL

1.5 mg/kg study drug (rhCC10)in 2 ml/kg given intratracheally times one dose

Drug: Low Dose rhCC10

High dose rhCC10

EXPERIMENTAL

5 mg/kg of rhCC10 given in 2 ml/kg and administered intratracheally times one dose

Drug: High dose rhCC10

Interventions

Half normal saline DRUG

2 ml/kg

half normal saline

Low Dose rhCC10 DRUG

1.5 mg/kg study drug (rhCC10)

Low Dose rhCC10

High dose rhCC10 DRUG

5 mg/kg in 2 ml/kg

High dose rhCC10

Eligibility Criteria

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

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tufts Medical Center: lead
• Brigham and Women's Hospital: collaborator
• Therabron Therapeutics, Inc.: collaborator
• Baystate Medical Center: collaborator
• Poznan University of Medical Sciences: collaborator
• SP ZOZ Szpital Uniwersytecki w Krakowie Oddizat Neonatologii: collaborator
• Instytut Centrum Zdrowia Matki Polki Klinika Neonatologii: collaborator

Study Sites (3)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

MeSH Terms

Conditions

Bronchopulmonary Dysplasia

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

Results Point of Contact

• Title: Jonathan M. Davis, MD
• Organization: Tufts Medical Center | Division of Newborn Medicine

jdavis@tuftsmedicalcenter.org

(617) 636-5322

Study Officials

• Jonathan Davis, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

• Richard Parad, MD/MPH

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2013
• First Posted: September 13, 2013
• Study Start: October 1, 2013
• Primary Completion: August 25, 2017
• Study Completion: August 25, 2017
• Last Updated: September 10, 2019
• Results First Posted: September 10, 2019

Record last verified: 2019-08

Locations

US (3)