Back to resultsA Double Blind, Randomized, Controlled Study to Evaluate CHF 5633 (Synthetic Surfactant) and Poractant Alfa in Neonates With Respiratory Distress Syndrome (RDS) (POC)
Primary Purpose
Respiratory Distress Syndrome, Newborn
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CHF5633
Poractant alfa
Sponsored by
About this trial
This is an interventional treatment trial for Respiratory Distress Syndrome, Newborn focused on measuring neonates, pulmonary surfactant
Eligibility Criteria
Inclusion Criteria:
- Written informed consent obtained by parents/legal representative (according to local regulation) prior to any study-related procedures
- Inborn preterm neonates of either sex with a gestational age of 24+0 weeks up to 29+6 weeks
- Clinical course consistent with RDS
- Requirement of endotracheal surfactant administration within 24 hours from birth
- Fraction of inspired oxygen (FiO2) ≥0.30 for babies 24+0 to 26+6 weeks and FiO2 ≥0.35 for babies 27+0 to 29+6 weeks to maintain SpO2 between 88-95%
Exclusion Criteria:
- Use of surfactant prior to study entry and need for intratracheal administration of any other treatment (e.g. nitric oxide)
- Known genetic or chromosomal disorders, major congenital anomalies (cardiac malformations, myelomeningocele etc)
- Maternal drug abuse (heroin, methadone, methamphetamine, or cocaine) or significant alcohol consumption during pregnancy
- Mothers with prolonged rupture of the membranes (>21 days duration)
- Strong suspicion of congenital pneumonia/infection, sepsis
- Presence of air leaks prior to study entry
- Evidence of severe birth asphyxia
- Neonatal seizures prior to study entry
- Any condition that, in the opinion of the Investigator, would place the neonate at undue risk
- Participation in another clinical trial of any placebo, drug or biological substance conducted under the provisions of a protocol.
Sites / Locations
- University of South Alabama - USA Children's and Women's Hospital
- LAC + USC Medical Center, Keck School of Medicine
- UC Irvine Medical Center
- Sharp Mary Birch Hospital
- Connecticut Children's Medical Center
- Plantation General Hospital (Sheridan Clinical Research, Inc.)
- Jatinder Bhatia
- Indiana University School of Medicine
- Memorial Hospital of South Bend
- University of Louisville Research Foundation, Inc.
- Floating Hospital for Children at Tufts Medical Center
- Baystate Children's Hospital / Baystate Medical Center
- Winthrop University Hospital
- Kings County Hospital Center
- Sergio G. Golombek
- Martha Naylor
- Cincinnati Children's Hospital Medical Center
- Case Western Reserve University
- Krishnamurthy Sekar
- Hahnemann University Hospital
- Texas Tech University Health Sciences Center
- MultiCare Institute for Research & Innovation
- West Virginia University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
CHF5633
Poractant alfa
Arm Description
Single dose within 24 hours from birth
Single dose within 24 hours from birth
Outcomes
Primary Outcome Measures
Oxygen Requirement and Ventilatory Support -- SpO2/FiO2 Ratio
SpO2/FiO2 ratio
The oxygen requirement and ventilatory support were assessed through arterial oxygen saturation, measured by pulse oximetry (SpO2 [%]) and ventilator settings, by measuring fraction of inspired oxygen (FiO2[%]) and SpO2/FiO2. Results are shown as change from baseline, summarized at post-treatment timepoints.
Definitions:
SpO2=Arterial Oxygen saturation by pulse oximetry; FiO2=Fraction of inspired oxygen; Baseline=The last pre-dose measurement taken on Day -1.
Fraction of Inspired Oxygen (FiO2) (Percent) During the First 24 h and up to Day 7
Fraction of inspired oxygen (FiO2) (percent) during the first 24 h and up to Day 7.
Fraction of inspired oxygen (FiO2 [percent]). Results are shown as change from baseline, summarized at post-treatment time points.
Definitions:
FiO2=Fraction of inspired oxygen (percent); Baseline=The last pre-dose measurement taken on Day -1;
Number of Patients With Bronchopulmonary Dysplasia and Mortality
Bronchopulmonary dysplasia and mortality.
Results summarize the following items:
Number of patients who died and the number of patients who had bronchopulmonary dysplasia (BPD) were assessed by treatment, at 36 weeks post menstrual age (PMA).
Number of patients who died by Day 28 post-natal age (PNA).
Number of patients with respiratory distress syndrome (RDS)-associated mortality by Day 14 post-natal age (PNA).
Definitions:
BPD=Bronchopulmonary dysplasia; Mortality/BPD incidence=The incidence of neonates dead within 36-week PMA or alive at 36-week PMA with a diagnosis of BPD; PMA=Post menstrual age; PNA=Post-natal age; RDS=Respiratory distress syndrome;
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02452476
Brief Title
A Double Blind, Randomized, Controlled Study to Evaluate CHF 5633 (Synthetic Surfactant) and Poractant Alfa in Neonates With Respiratory Distress Syndrome (RDS) (POC)
Official Title
A DOUBLE BLIND, RANDOMIZED, CONTROLLED STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF SYNTHETIC SURFACTANT (CHF 5633) IN COMPARISON TO PORCINE SURFACTANT (PORACTANT ALFA, CUROSURF®) IN THE TREATMENT OF PRETERM NEONATES WITH RESPIRATORY DISTRESS SYNDROME
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
January 21, 2016 (Actual)
Primary Completion Date
May 24, 2018 (Actual)
Study Completion Date
May 24, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chiesi Farmaceutici S.p.A.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A multicenter, double blind, randomized, single dose, active-controlled study to investigate the efficacy and safety of synthetic surfactant (CHF 5633) in comparison to porcine surfactant (Poractant alfa, Curosurf ®) in the treatment of preterm neonates with respiratory distress syndrome. Main objectives of this study are to investigate the short term efficacy profile of CHF 5633 vs. porcine surfactant (Poractant Alfa, Curosurf®) in terms of reduced oxygen requirement and ventilatory support and to evaluate the mid-term efficacy profile in terms of reduced incidence of bronchopulmonary dysplasia (BPD) and mortality/BPD rate at 36 weeks post menstrual age (PMA), mortality rate at 28 days and 36 weeks PMA, RDS-associated mortality through 14 days of age and other major co-morbidities of prematurity.
Inclusion criteria are: Written parental informed consent, inborn preterm neonates of either sex with a gestational age of 24+0 weeks up to 29+6 weeks, clinical course consistent with RDS, requirement of endotracheal surfactant administration within 24 hours from birth, fraction of inspired oxygen (FiO2) ≥0.30 for babies 24+0 to 26+6 weeks and FiO2 ≥0.35 for babies 27+0 to 29+6 weeks to maintain arterial oxygen saturation by pulse oximetry (SpO2) between 88-95%.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Respiratory Distress Syndrome, Newborn
Keywords
neonates, pulmonary surfactant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
123 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CHF5633
Arm Type
Experimental
Arm Description
Single dose within 24 hours from birth
Arm Title
Poractant alfa
Arm Type
Active Comparator
Arm Description
Single dose within 24 hours from birth
Intervention Type
Drug
Intervention Name(s)
CHF5633
Intervention Description
Rescue treatment (if needed)
Intervention Type
Drug
Intervention Name(s)
Poractant alfa
Intervention Description
Rescue treatment (if needed)
Primary Outcome Measure Information:
Title
Oxygen Requirement and Ventilatory Support -- SpO2/FiO2 Ratio
Description
SpO2/FiO2 ratio
The oxygen requirement and ventilatory support were assessed through arterial oxygen saturation, measured by pulse oximetry (SpO2 [%]) and ventilator settings, by measuring fraction of inspired oxygen (FiO2[%]) and SpO2/FiO2. Results are shown as change from baseline, summarized at post-treatment timepoints.
Definitions:
SpO2=Arterial Oxygen saturation by pulse oximetry; FiO2=Fraction of inspired oxygen; Baseline=The last pre-dose measurement taken on Day -1.
Time Frame
Post-treatment Day 1: 30 min, at 1h, 3h, 6h, 12h, 18h, 24 h; Day 2, 3, 5, and 7
Title
Fraction of Inspired Oxygen (FiO2) (Percent) During the First 24 h and up to Day 7
Description
Fraction of inspired oxygen (FiO2) (percent) during the first 24 h and up to Day 7.
Fraction of inspired oxygen (FiO2 [percent]). Results are shown as change from baseline, summarized at post-treatment time points.
Definitions:
FiO2=Fraction of inspired oxygen (percent); Baseline=The last pre-dose measurement taken on Day -1;
Time Frame
Post-treatment Day 1: 30 min, at 1h, 3h, 6h, 12h, 18h, 24 h; Day 2, 3, 5, and 7
Title
Number of Patients With Bronchopulmonary Dysplasia and Mortality
Description
Bronchopulmonary dysplasia and mortality.
Results summarize the following items:
Number of patients who died and the number of patients who had bronchopulmonary dysplasia (BPD) were assessed by treatment, at 36 weeks post menstrual age (PMA).
Number of patients who died by Day 28 post-natal age (PNA).
Number of patients with respiratory distress syndrome (RDS)-associated mortality by Day 14 post-natal age (PNA).
Definitions:
BPD=Bronchopulmonary dysplasia; Mortality/BPD incidence=The incidence of neonates dead within 36-week PMA or alive at 36-week PMA with a diagnosis of BPD; PMA=Post menstrual age; PNA=Post-natal age; RDS=Respiratory distress syndrome;
Time Frame
36 weeks post menstrual age, Day 14 Post-Natal Age, Day 28 Post-Natal Age
Other Pre-specified Outcome Measures:
Title
Number of Patients With Normal Breathing (Room Air) Within 24 Hours
Description
Normal breathing (room air) within 24 hours
The number of patients with at least one reading of FiO2 equal to 21% (i.e. corresponding to room air for oxygen concentration) within 24 hours from first dose of surfactant was evaluated.
Time Frame
Post-treatment up to 24 h
Title
Number of Patients With the Need for Re-dosing (Use of Rescue Surfactant)
Description
Number of patients with the need for re-dosing (use of rescue surfactant).
The number of patients requiring at least one surfactant rescue dose (i.e. re-dosing with the study drug) at any time during the study was evaluated.
Time Frame
Day 1 to Day 7
Title
Time to Reach Normal Breathing (Room Air) Within 24 Hours
Description
Time to reach normal breathing (room air) within 24 hours.
The median time to reach normal breathing (room air) within 24 hours from first dose of surfactant was evaluated. These are the patients who contributed to the results in the outcome measure 'Normal Breathing (room air) within 24 hours'.
Time Frame
Post-treatment Day 1: up to 24 h
Title
Concentration of Biomarkers of Inflammation in Tracheal Aspirates
Description
The inflammatory status of the patients was assessed (in a subgroup of babies who required endotracheal intubation for mechanical ventilation, when feasible). This was performed by measuring the concentration of specific biomarkers of inflammation in tracheal aspirates. The biomarkers measured were: Interleukin 1β, Interleukin 6, Interleukin 8, Myeloperoxidase, and Tumor Necrosis Factor-Alpha.
The total protein content in tracheal aspirates was measured as an endogenous marker of dilution to calculate the extent to which epithelial lining fluid (ELF) was diluted during the tracheal aspirate procedure. To adjust for variation during the collection of tracheal aspirates, the measured cytokines values were normalized to the total protein. Results are presented as change from baseline in pg/mg total protein and were evaluated by descriptive statistics.
Definition:
Baseline=The last pre-dose measurement taken on Day -1;
Time Frame
Post-treatment Day 1 (24 h), Day 2 (48 h)
Title
Immunogenicity: Assessment of Antibodies to Surfactant Protein B (SP-B) Analogue (CHF 5736.03) and to Surfactant Protein C (SP-C) Analogue (CHF 4902.03)
Description
Immunogenicity was assessed by measuring antibodies to SP-B analogue (CHF 5736.03) and to SP-C analogue (CHF 4902.03), contained in CHF 5633.
Results are expressed as the titre (i.e. serum dilution) at which the sample had an absorbance of 0.069 (background) for SP-C Analogue (CHF 4902.03) CHF or an absorbance of 0.05 for SP-B Analogue (CHF 5736.03) in a microplate reader. The positive control serum was diluted in buffer solution and the maximum binding for the positive control was determined at dilutions < 1/12.5 for SPC and <1/100 for SPB. Test samples for immunogenicity were analyzed by using negative and positive controls. By definition, titer <12.5 for CHF-4902.03 and <100 for CHF-5736.02 show that the test serum had an absorbance equal to background at the same dilution at which the positive control had the maximum binding, implying absence of antibodies.
Time Frame
At approximately 5 weeks after the administration of study drug (with a range from 3 to 6 weeks).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Hour
Maximum Age & Unit of Time
24 Hours
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent obtained by parents/legal representative (according to local regulation) prior to any study-related procedures
Inborn preterm neonates of either sex with a gestational age of 24+0 weeks up to 29+6 weeks
Clinical course consistent with RDS
Requirement of endotracheal surfactant administration within 24 hours from birth
Fraction of inspired oxygen (FiO2) ≥0.30 for babies 24+0 to 26+6 weeks and FiO2 ≥0.35 for babies 27+0 to 29+6 weeks to maintain SpO2 between 88-95%
Exclusion Criteria:
Use of surfactant prior to study entry and need for intratracheal administration of any other treatment (e.g. nitric oxide)
Known genetic or chromosomal disorders, major congenital anomalies (cardiac malformations, myelomeningocele etc)
Maternal drug abuse (heroin, methadone, methamphetamine, or cocaine) or significant alcohol consumption during pregnancy
Mothers with prolonged rupture of the membranes (>21 days duration)
Strong suspicion of congenital pneumonia/infection, sepsis
Presence of air leaks prior to study entry
Evidence of severe birth asphyxia
Neonatal seizures prior to study entry
Any condition that, in the opinion of the Investigator, would place the neonate at undue risk
Participation in another clinical trial of any placebo, drug or biological substance conducted under the provisions of a protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rangasamy Ramanathan, MD
Organizational Affiliation
Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center and Good Samaritan Hospital, Keck School of Medicine of USC, Los Angeles, CA, USA
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of South Alabama - USA Children's and Women's Hospital
City
Mobile
State/Province
Alabama
Country
United States
Facility Name
LAC + USC Medical Center, Keck School of Medicine
City
Los Angeles
State/Province
California
Country
United States
Facility Name
UC Irvine Medical Center
City
Orange
State/Province
California
Country
United States
Facility Name
Sharp Mary Birch Hospital
City
San Diego
State/Province
California
Country
United States
Facility Name
Connecticut Children's Medical Center
City
Hartford
State/Province
Connecticut
Country
United States
Facility Name
Plantation General Hospital (Sheridan Clinical Research, Inc.)
City
Plantation
State/Province
Florida
Country
United States
Facility Name
Jatinder Bhatia
City
Augusta
State/Province
Georgia
Country
United States
Facility Name
Indiana University School of Medicine
City
Indianapolis
State/Province
Indiana
Country
United States
Facility Name
Memorial Hospital of South Bend
City
South Bend
State/Province
Indiana
Country
United States
Facility Name
University of Louisville Research Foundation, Inc.
City
Louisville
State/Province
Kentucky
Country
United States
Facility Name
Floating Hospital for Children at Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Baystate Children's Hospital / Baystate Medical Center
City
Springfield
State/Province
Massachusetts
Country
United States
Facility Name
Winthrop University Hospital
City
Mineola
State/Province
New York
Country
United States
Facility Name
Kings County Hospital Center
City
New York
State/Province
New York
Country
United States
Facility Name
Sergio G. Golombek
City
Valhalla
State/Province
New York
Country
United States
Facility Name
Martha Naylor
City
Greenville
State/Province
North Carolina
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
Country
United States
Facility Name
Krishnamurthy Sekar
City
Oklahoma City
State/Province
Oklahoma
Country
United States
Facility Name
Hahnemann University Hospital
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
Texas Tech University Health Sciences Center
City
El Paso
State/Province
Texas
Country
United States
Facility Name
MultiCare Institute for Research & Innovation
City
Tacoma
State/Province
Washington
Country
United States
Facility Name
West Virginia University
City
Morgantown
State/Province
West Virginia
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32553868
Citation
Ramanathan R, Biniwale M, Sekar K, Hanna N, Golombek S, Bhatia J, Naylor M, Fabbri L, Varoli G, Santoro D, Del Buono D, Piccinno A, Dammann CE. Synthetic Surfactant CHF5633 Compared with Poractant Alfa in the Treatment of Neonatal Respiratory Distress Syndrome: A Multicenter, Double-Blind, Randomized, Controlled Clinical Trial. J Pediatr. 2020 Oct;225:90-96.e1. doi: 10.1016/j.jpeds.2020.06.024. Epub 2020 Jun 14. Erratum In: J Pediatr. 2020 Nov 10;: J Pediatr. 2022 May;244:262.
Results Reference
result
Learn more about this trial
A Double Blind, Randomized, Controlled Study to Evaluate CHF 5633 (Synthetic Surfactant) and Poractant Alfa in Neonates With Respiratory Distress Syndrome (RDS) (POC)
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