CompletedNCT01941745Updated Sep 10, 2019Results posted

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

A Phase 2 interventional study of Half normal saline and Low Dose rhCC10 in Respiratory Distress Syndrome in Premature Infant and Bronchopulmonary Dysplasia, sponsored by Tufts Medical Center. Completed at 3 sites in United States. Open to participants aged 24 Weeks to 29 Weeks. Per ClinicalTrials.gov, last updated 2019-09-10.

Sponsored by Tufts Medical Center · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 88
Allocation: Randomized
Ages: 24 Weeks to 29 Weeks
Sex: All

Study 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).

Read the detailed description

Recombinant human CC10 protein (rhCC10) is a novel therapeutic agent used to prevent the development of chronic respiratory morbidity (CPIP; repeated respiratory infections, asthma, re-hospitalizations) in preterm infants. Native CC10 is a natural anti-inflammatory and immunomodulatory factor produced by Clara Cells in the lung and is the most abundant protein in respiratory mucosa. Animal data demonstrate that a single intratracheal dose of rhCC10 administered shortly after birth reduces lung inflammation (important biomarkers linked to lung injury in preterm infants), promotes normal lung development, preserves lung architecture, improves pulmonary function, suppresses the response to endotoxin and enhances resistance to pulmonary infections. In preterm infants who die or develop lung inflammation and subsequent bronchopulmonary dysplasia (BPD), both the concentration and activity of CC10 are significantly reduced indicating that CC10 is essential for preventing lung injury and promoting normal lung development. In a small phase I study, rhCC10 significantly decreased several indices of pulmonary inflammation in the lungs of premature infants who were at risk of developing BPD and associated CPIP. The drug appeared to be safe, well-tolerated, and reduce risk of re-hospitalization due to respiratory illness for 9-10 months after a single intratracheal dose at the time of birth (0/11 rhCC10-treated infants vs. 3/6 placebo-treated). This supports the protective role of rhCC10 against damage from hyperoxia, mechanical ventilation, inflammation, and infection in the immature lung. A more normal airway epithelium will produce significantly more endogenous CC10, with both factors contributing to enhanced resistance to infections, less asthma, and improved long-term respiratory outcome. We propose to conduct a Phase 2 clinical trial to evaluate rhCC10 in extremely premature infants (\<29 weeks gestation) for the prevention of BPD and CPIP. This will be a randomized, double-blind, placebo-controlled dose escalation study in 88 premature infants. A single intratracheal dose of study drug (rhCC10 or placebo) will be administered to preterm infants receiving surfactant and mechanical ventilation for treatment of RDS. Infants will be followed to evaluate safety, pharmacokinetics, and short and long term efficacy of this approach. Safety will be evaluated through serious adverse event (SAE) and adverse event monitoring and by Bayley neurodevelopmental assessments at 18 months corrected gestational age (CGA). Efficacy measurements will include the primary combined endpoint of alive without evidence of CPIP through 12 months CGA (defined by parental diaries and pulmonary questionnaires) comparing rhCC10 treated to placebo controls. The availability of a therapy which prevents lung injury, promotes lung development, and prevents serious respiratory infections and asthma in high risk preterm infants would be a highly significant advancement in care.

Conditions studied

Respiratory Distress Syndrome in Premature Infant
Bronchopulmonary Dysplasia

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Bronchopulmonary Dysplasia 344

In context

Bronchopulmonary Dysplasia

344 studies on the registry are indexed under Bronchopulmonary Dysplasia; 81 are open to participants now.

This study's enrollment of 88 is above the median of 70 across 230 interventional studies indexed under Bronchopulmonary Dysplasia.

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Lead sponsor

Tufts Medical Center is the lead sponsor of 200 studies on the registry; 28 are open to participants now.

Of its 32 completed or terminated interventional studies of FDA-regulated products, 16 (50%) have results posted.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 24 Weeks to 29 Weeks
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Care provider, Investigator)
Enrollment: 88 participants (actual)

Study arms

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

Interventions

DrugHalf normal saline
2 ml/kg
DrugLow Dose rhCC10
1.5 mg/kg study drug (rhCC10)
DrugHigh dose rhCC10
5 mg/kg in 2 ml/kg

What researchers measure

Primary outcomes

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).
Time frame: 12 Months Corrected Gestational Age (*no imputation for missing data)

Secondary outcomes

Long Term Efficacy - Survival Without Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 6 Months Corrected Gestational Age (CGA)
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).
Time frame: 6 months Corrected Gestational Age
Safety and Efficacy - Number of Participants With Adverse Events
The safety of the study drug was assessed by accounting the number of participants with Adverse Events (AEs) in the treatment and placebo groups.
Time frame: 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
Short term efficacy evaluations involve number of neonates with oxygen requirement at 36 weeks post menstrual age.
Time frame: 36 weeks post-menstrual age

Results

Posted Sep 10, 2019

Participant flow

Recruitment spanned October 2013 - August 2017 at ICUs at Tufts Medical Center (Boston, MA), Brigham and Women's Hospital (Boston, MA), and BayState Medical Center (Springfield, MA). Three hospital sites in Poland were later added for the second high-dose/high dose placebo cohort of 44 neonates.

Participant flow — Overall Study
Milestone	Placebo (Associated w/ Low Dose Cohort)	Low Dose (rhCC10)	Placebo (Associated w/ High Dose Cohort)	High Dose (rhCC10)
Started	22	22	21	23
Completed	22	22	21	23
Not completed	0	0	0	0

Outcome measures

PrimarySurvival 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).

Time frame:: 12 Months Corrected Gestational Age (*no imputation for missing data)
Reported as:: Number · Number of events

Survival Without Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 12 Months Corrected Gestational Age (CGA)
Number of events	Placebo (Associated w/ Low Dose Cohort)	Low Dose (rhCC10)	Placebo (Associated w/ High Dose Cohort)	High Dose (rhCC10)
Survived with no CPIP-DV (Medical/ER visits)	8	2	6	6
Survived with no CPIP-RH	20	12	11	10
Survived with no CPIP-SS (Respiratory Symptoms)	2	3	6	5
Survived with no CPIP-RM (Respiratory Medications	10	7	6	5
Survived with no CPIP events (-DV, -RH, -SS, -RM)	1	1	3	3

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

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).

Time frame:: 6 months Corrected Gestational Age
Reported as:: Number · Number of Events

Long Term Efficacy - Survival Without Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 6 Months Corrected Gestational Age (CGA)
Number of Events	Placebo (Associated w/ Low Dose Cohort)	Low Dose (rhCC10)	Placebo (Associated w/ High Dose Cohort)	High Dose (rhCC10)
Survived without 1 CPIP component	4	3	7	4
Survived without 2 CPIP components	10	6	8	7
Survived without 3 CPIP components	15	11	10	10
Survived without 4 CPIP components	21	16	17	14

SecondarySafety and Efficacy - Number of Participants With Adverse Events

The safety of the study drug was assessed by accounting the number of participants with Adverse Events (AEs) in the treatment and placebo groups.

Time frame:: Adverse events are monitored through 36 wks post-menstrual age (PMA)
Reported as:: Count of participants · Participants

Safety and Efficacy - Number of Participants With Adverse Events
Participants	Placebo (Associated w/ Low Dose Cohort)	Low Dose (rhCC10)	Placebo (Associated w/ High Dose Cohort)	High Dose (rhCC10)
Safety and Efficacy - Number of Participants With Adverse Events	22	22	21	23

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

Short term efficacy evaluations involve number of neonates with oxygen requirement at 36 weeks post menstrual age.

Time frame:: 36 weeks post-menstrual age
Reported as:: Count of participants · Participants

Short Term Efficacy - Number of Neonates With Oxygen Requirement at 36 Weeks Post Menstrual Age
Participants	Placebo (Associated w/ Low Dose Cohort)	Low Dose rhCC10	Placebo (Associated w/ High Dose Cohort)	High Dose rhCC10
Short Term Efficacy - Number of Neonates With Oxygen Requirement at 36 Weeks Post Menstrual Age	8	10	8	4

Adverse events

Collected over A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Placebo (Associated w/ Low Dose Cohort)	0/22 (0%)	16/22 (72.7%)	22/22 (100%)
Low Dose (rhCC10)	2/22 (9.1%)	17/22 (77.3%)	22/22 (100%)
Placebo (Associated w/ High Dose Cohort)	2/21 (9.5%)	17/21 (81%)	21/21 (100%)
High Dose (rhCC10)	5/23 (21.7%)	19/23 (82.6%)	23/23 (100%)

Most frequent serious events

Showing 10 of 15

Most frequent serious events
Event	Placebo (Associated w/ Low Dose Cohort)	Low Dose (rhCC10)	Placebo (Associated w/ High Dose Cohort)	High Dose (rhCC10)
Respiratory InfectionsInfections and infestations	5/22	3/22	9/21	9/23
ROP Stage 3Eye disorders	5/22	1/22	3/21	4/23
ApneaRespiratory, thoracic and mediastinal disorders	4/22	5/22	1/21	0/23
SepsisInfections and infestations	1/22	3/22	3/21	5/23
IVH grade 3-4Nervous system disorders	0/22	1/22	4/21	4/23
Respiratory DistressRespiratory, thoracic and mediastinal disorders	1/22	2/22	0/21	4/23
PVLNervous system disorders	0/22	0/22	3/21	0/23
NEC Stage II-IIIGastrointestinal disorders	3/22	1/22	2/21	2/23
PDACongenital, familial and genetic disorders	0/22	1/22	2/21	3/23
Pulmonary HemorrhageRespiratory, thoracic and mediastinal disorders	1/22	1/22	2/21	2/23

Most frequent other events

Showing 10 of 32

Most frequent other events
Event	Placebo (Associated w/ Low Dose Cohort)	Low Dose (rhCC10)	Placebo (Associated w/ High Dose Cohort)	High Dose (rhCC10)
ApneaRespiratory, thoracic and mediastinal disorders	22/22	17/22	10/21	11/23
AnemiaBlood and lymphatic system disorders	10/22	8/22	16/21	18/23
HyperbilirubinemiaHepatobiliary disorders	15/22	11/22	11/21	15/23
PDA +ASDCongenital, familial and genetic disorders	7/22	9/22	13/21	14/23
IVH Grades I-IVNervous system disorders	3/22	7/22	9/21	11/23
HyperglycemiaMetabolism and nutrition disorders	4/22	3/22	10/21	8/23
Metabolic AcidosisMetabolism and nutrition disorders	8/22	4/22	6/21	9/23
HypotensionVascular disorders	2/22	2/22	5/21	9/23
PneumoniaInfections and infestations	3/22	1/22	8/21	4/23
ROP Stages I-IVEye disorders	7/22	2/22	6/21	8/23

Baseline characteristics

Baseline populations were recruited from Tufts Medical Center and Brigham and Women's Hospital. Sites with a second high-dose cohort include BayState Medical Center, Ginekologiczno-Położniczy Szpital Kliniczny UM, Instytut Centrum Zdrowia Matki Polski and Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie (US, Poland).

Age, Customized
Age, Customized(weeks)	Placebo (Associated w/ Low Dose Cohort)	Low Dose (rhCC10)	Placebo (Associated w/ High Dose Cohort)	High Dose (rhCC10)	Total
Mean	26.1 ± 1.3	26.5 ± 1.1	27.0 ± 1.3	26.6 ± 1.2	26.6 ± 1.2

Sex: Female, Male
Sex: Female, Male(Participants)	Placebo (Associated w/ Low Dose Cohort)	Low Dose (rhCC10)	Placebo (Associated w/ High Dose Cohort)	High Dose (rhCC10)	Total
Female	12	8	8	12	40
Male	10	14	13	11	48

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Placebo (Associated w/ Low Dose Cohort)	Low Dose (rhCC10)	Placebo (Associated w/ High Dose Cohort)	High Dose (rhCC10)	Total
Hispanic or Latino	5	7	5	5	22
Not Hispanic or Latino	0	0	0	0	0
Unknown or Not Reported	17	15	16	18	66

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Placebo (Associated w/ Low Dose Cohort)	Low Dose (rhCC10)	Placebo (Associated w/ High Dose Cohort)	High Dose (rhCC10)	Total
American Indian or Alaska Native	0	0	0	0	0
Asian	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	0	0	0	0	0
White	9	12	15	18	54
More than one race	0	0	0	0	0
Unknown or Not Reported	13	10	6	5	34

Region of Enrollment
Region of Enrollment(participants)	Placebo (Associated w/ Low Dose Cohort)	Low Dose (rhCC10)	Placebo (Associated w/ High Dose Cohort)	High Dose (rhCC10)	Total
United States	22	22	10	11	65
Poland	0	0	11	12	22

Mean birth weight
Mean birth weight(grams)	Placebo (Associated w/ Low Dose Cohort)	Low Dose (rhCC10)	Placebo (Associated w/ High Dose Cohort)	High Dose (rhCC10)	Total
Mean	877.4 ± 170.9	859.3 ± 140.9	885.5 ± 173.9	867.2 ± 187.2	874.5 ± 168.2

Median 5 min APGAR score
Median 5 min APGAR score(Scores on a scale)	Placebo (Associated w/ Low Dose Cohort)	Low Dose (rhCC10)	Placebo (Associated w/ High Dose Cohort)	High Dose (rhCC10)	Total
Median	8 (7 to 8)	7 (6 to 8)	7 (7 to 8)	7 (6 to 8)	7 (7 to 8)

Study locations

3 sites

Tufts Medical Center
Boston, Massachusetts 02111, United States
Brigham and Women's Hospital
Boston, Massachusetts 02115, United States
Baystate Medical Center
Springfield, Massachusetts 01199, United States

References and documents

Study documents

Protocol and statistical analysis plan · Oct 1, 2015

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 10, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01941745
Lead sponsor: Tufts Medical Center
Collaborators: Brigham and Women's Hospital, Therabron Therapeutics, Inc., Baystate Medical Center, Poznan University of Medical Sciences, SP ZOZ Szpital Uniwersytecki w Krakowie Oddizat Neonatologii, Instytut Centrum Zdrowia Matki Polki Klinika Neonatologii
Responsible party: Sponsor
First posted: Sep 13, 2013
Start date: Oct 2013
Primary completion: Aug 25, 2017
Completion: Aug 25, 2017
Results posted: Sep 10, 2019
Last update: Sep 10, 2019

Study contacts

Jonathan Davis, MD

principal investigator · Tufts Medical Center

Richard Parad, MD/MPH

principal investigator · Brigham and Women's Hospital

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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