A Double Blind, Randomized, Controlled Study to Evaluate CHF 5633 (Synthetic Surfactant) and Poractant Alfa in Neonates With Respiratory Distress Syndrome (RDS) (POC)

Respiratory Distress Syndrome, Newborn Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02452476
• Other study ID #: CCD-05633AA1-02
• Status: Completed
• Phase: Phase 2
• Start date: January 21, 2016
• Est. completion date: May 24, 2018

Study information

• Verified date: July 2021
• Source: Chiesi Farmaceutici S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: May 24, 2018
• Est. primary completion date: May 24, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 24 Hours

Eligibility

Inclusion Criteria:

1. Written informed consent obtained by parents/legal representative (according to local regulation) prior to any study-related procedures

2. Inborn preterm neonates of either sex with a gestational age of 24+0 weeks up to 29+6 weeks

3. Clinical course consistent with RDS

4. Requirement of endotracheal surfactant administration within 24 hours from birth

5. 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:

1. Use of surfactant prior to study entry and need for intratracheal administration of any other treatment (e.g. nitric oxide)

2. Known genetic or chromosomal disorders, major congenital anomalies (cardiac malformations, myelomeningocele etc)

3. Maternal drug abuse (heroin, methadone, methamphetamine, or cocaine) or significant alcohol consumption during pregnancy

4. Mothers with prolonged rupture of the membranes (>21 days duration)

5. Strong suspicion of congenital pneumonia/infection, sepsis

6. Presence of air leaks prior to study entry

7. Evidence of severe birth asphyxia

8. Neonatal seizures prior to study entry

9. Any condition that, in the opinion of the Investigator, would place the neonate at undue risk

10. Participation in another clinical trial of any placebo, drug or biological substance conducted under the provisions of a protocol.

Related Conditions & MeSH terms

• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Drug:
• CHF5633
Rescue treatment (if needed)
• Poractant alfa
Rescue treatment (if needed)

Locations

Country	Name	City	State
United States	Jatinder Bhatia	Augusta	Georgia
United States	Floating Hospital for Children at Tufts Medical Center	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Texas Tech University Health Sciences Center	El Paso	Texas
United States	Martha Naylor	Greenville	North Carolina
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	LAC + USC Medical Center, Keck School of Medicine	Los Angeles	California
United States	University of Louisville Research Foundation, Inc.	Louisville	Kentucky
United States	Winthrop University Hospital	Mineola	New York
United States	University of South Alabama - USA Children's and Women's Hospital	Mobile	Alabama
United States	West Virginia University	Morgantown	West Virginia
United States	Kings County Hospital Center	New York	New York
United States	Krishnamurthy Sekar	Oklahoma City	Oklahoma
United States	UC Irvine Medical Center	Orange	California
United States	Hahnemann University Hospital	Philadelphia	Pennsylvania
United States	Plantation General Hospital (Sheridan Clinical Research, Inc.)	Plantation	Florida
United States	Sharp Mary Birch Hospital	San Diego	California
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Baystate Children's Hospital / Baystate Medical Center	Springfield	Massachusetts
United States	MultiCare Institute for Research & Innovation	Tacoma	Washington
United States	Sergio G. Golombek	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Chiesi Farmaceutici S.p.A.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Syn — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Patients With Normal Breathing (Room Air) Within 24 Hours	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.	Post-treatment up to 24 h
Other	Number of Patients With the Need for Re-dosing (Use of Rescue Surfactant)	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.	Day 1 to Day 7
Other	Time to Reach Normal Breathing (Room Air) Within 24 Hours	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'.	Post-treatment Day 1: up to 24 h
Other	Concentration of Biomarkers of Inflammation in Tracheal Aspirates	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 1ß, 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;	Post-treatment Day 1 (24 h), Day 2 (48 h)
Other	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)	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.	At approximately 5 weeks after the administration of study drug (with a range from 3 to 6 weeks).
Primary	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.	Post-treatment Day 1: 30 min, at 1h, 3h, 6h, 12h, 18h, 24 h; Day 2, 3, 5, and 7
Primary	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;	Post-treatment Day 1: 30 min, at 1h, 3h, 6h, 12h, 18h, 24 h; Day 2, 3, 5, and 7
Primary	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;	36 weeks post menstrual age, Day 14 Post-Natal Age, Day 28 Post-Natal Age