Poractant Alfa - Curosurf and SARS-COV-19 ARDS (Covid-19)

• ClinicalTrials.gov Identifier: NCT04502433
• Recruitment Status: Terminated
• First Posted: August 6, 2020
• Last Update Posted: April 6, 2022
• Sponsor: Chiesi Farmaceutici S.p.A.
• Information provided by (Responsible Party): Chiesi Farmaceutici S.p.A.

Tracking Information

• First Submitted Date: August 3, 2020
• First Posted Date: August 6, 2020
• Last Update Posted Date: April 6, 2022
• Actual Study Start Date: January 6, 2021
• Actual Primary Completion Date: March 18, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 3, 2021)

Number of days alive and ventilator-free days [ Time Frame: up to 21 days ]

The primary outcome variable will be the number of days alive and ventilator-free days, defined as the number of days the patient is not receiving mechanical ventilation during the 21 days following randomisation.

Original Primary Outcome Measures (submitted: August 5, 2020)

number of ventilator-free days [ Time Frame: up to 21 days ]

The primary outcome variable will be the number of ventilator-free days, defined as the number of days the patient is not receiving mechanical ventilation during the 21 days following randomisation.

Current Secondary Outcome Measures (submitted: August 3, 2021)

• Number of days alive and free from invasive ventilation [ Time Frame: at Day 21 day and at Day 28 ]
• Number of alive and free days from non-invasive ventilation (NIV) [ Time Frame: at Day 21 day and at Day 28 ]
• Change from baseline in PaO2/FiO2 ratio measured at 6 hours and 12 hours following administration of each dose in the treated group and at the similar time points in the control group [ Time Frame: 6, 12, 30, 36, 54 and 60 hours after randomisation ]
• Change from baseline in PaO2/FiO2 ratio at additional timepoints [ Time Frame: every 24 hours after treatment/randomisation until the patient is discharged from the ICU . Up to 28 days ]
• Length of ICU stay (days) [ Time Frame: up to 28 days ]
• Change from baseline in ventilatory parameter (Tidal volume- TV) [ Time Frame: up to 28 days ]
• Delta Sequential Organ Failure Assessment (SOFA) Score and sub-component measure [ Time Frame: Day3, and Day 28 or discharge whichever comes first ]
  min score 0 max score 24
• Incidence of all the AEs, AEs related to poractant alfa (treated cohort) (ADRs), serious AEs (SAEs) and AEs leading to death [ Time Frame: up to 28 days ]
• Change from baseline in blood gas analysis acid-base balance parameters (pH) [ Time Frame: up to 28 days ]
  Measured at 6-12-24h after each poractant alfa administration up to 72 hours and at similar timepoints in the control group (6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation) and then every 24 hours till the patient is discharged from the ICU
• Percentage of patients alive and with PaO2/ FiO2 improvement of >20% following administration of each dose in the treated group and at similar timepoints in the control group [ Time Frame: at 6 and 12 hours following administration each dose in the treated group and at similar timepoints in the control group = up to 60 hours after the randomization ]
• Percentage of patients alive and with PaO2/ FiO2 improvement of >20% following at the additional timepoints administration of each dose in the treated group and at similar time points in the control group [ Time Frame: through study completion, up to 28 days ]
• Change from baseline in FiO2 [ Time Frame: (6, 12, 30, 36, 54 and 60 hours after randomisation + every 24 hours after treatment/randomisation until the patient is discharged from the ICU = up to 28 days ]
• Change from baseline in ventilatory parameter (respiratory rate (RR)) [ Time Frame: up to 28 days ]
• Change from baseline in ventilatory parameter (dynamic compliance (Cdyn)) [ Time Frame: up to 28 days ]
• Change from baseline in ventilatory parameter (static compliance (Cstat)) [ Time Frame: up to 28 days ]
• Change from baseline in ventilatory parameter (positive end-expiratory pressure (PEEP) [ Time Frame: up to 28 days ]
• Change from baseline in ventilatory parameter (peak inspiratory pressure (PIP)) [ Time Frame: up to 28 days ]
• Change from baseline in ventilatory parameter (plateau pressure (Pplat)) [ Time Frame: up to 28 days ]
• Change from baseline in blood gas analysis acid-base balance parameter (pCO2) [ Time Frame: up to 28 days ]
• Change from baseline in blood gas analysis acid-base balance parameter (pO2) [ Time Frame: up to 28 days ]
• Change from baseline in blood gas analysis acid-base balance parameter (HCO3) [ Time Frame: up to 28 days ]
• Change from baseline in blood gas analysis acid-base balance parameter (lactate) [ Time Frame: up to 28 days ]
• Mortality [ Time Frame: up to day 28 ]
• Percentage of patients with improvement in severity status defined as a decrease in the severity score [ Time Frame: up to day 28 or discharge, whichever comes first ]
• Percentage of patients alive and out of ICU [ Time Frame: Day 28 ]
• Percentage of patients alive and free of organ failure [ Time Frame: at day 28 or discharge whichever comes first ]
• Percentage of patients alive and free of respiratory failure [ Time Frame: at Day 28 ]
• Number of days alive and ventilatory-free [ Time Frame: at day 28 ]

Original Secondary Outcome Measures (submitted: August 5, 2020)

• Number of free days from invasive ventilation [ Time Frame: up to 21 days ]
• Number of free days from non-invasive ventilation (NIV) [ Time Frame: up to 21 days ]
• Change from baseline in PaO2/FiO2 ratio measured at 6 hours and 12 hours following administration of each dose in the treated group and at the similar timepoints in the control group [ Time Frame: 6, 12, 30, 36, 54 and 60 hours after randomisation ]
• Change from baseline in PaO2/FiO2 ratio at additional timepoints [ Time Frame: every 24 hours after treatment/randomisation until the patient is discharged from the ICU . Up to 28 days ]
• Length of ICU stay (days) [ Time Frame: up to 28 days ]
• Mortality at Day 28 [ Time Frame: Day 28 ]
• Change from baseline in ventilatory parameter (Tidal volume (TV)) [ Time Frame: up to 28 days ]
• Delta Sequential Organ Failure Assessment (SOFA) Score [ Time Frame: up to 28 days ]
  min score 0 max score 24
• Incidence of all the AEs, AEs related to poractant alfa (treated cohort) (ADRs), serious AEs (SAEs) and AEs leading to death [ Time Frame: up to 28 days ]
• Change from baseline in blood gas analysis acid-base balance parameter (pH) [ Time Frame: up to 28 days ]
• Percentage of patients with PaO2/ FiO2 improvement of >20% following administration of each dose in the treated group and at similar timepoints in the control group [ Time Frame: at 6 and 12 hours following administration each dose in the treated group and at similar timepoints in the control group = up to 60 hours after the randomization ]
• Number of Extracorporeal Membrane Oxygenation (ECMO)-free days- (only for cohort 2 of patients in ECMO) [ Time Frame: 21 days after randomization ]
• Change from baseline in FiO2 [ Time Frame: (6, 12, 30, 36, 54 and 60 hours after randomisation + every 24 hours after treatment/randomisation until the patient is discharged from the ICU = up to 28 days ]
• Change from baseline in ventilatory parameter (respiratory rate (RR)) [ Time Frame: up to 28 days ]
• Change from baseline in ventilatory parameter (dynamic compliance (Cdyn)) [ Time Frame: up to 28 days ]
• Change from baseline in ventilatory parameter (static compliance (Cstat)) [ Time Frame: up to 28 days ]
• Change from baseline in ventilatory parameter (positive end-expiratory pressure (PEEP) [ Time Frame: up to 28 days ]
• Change from baseline in ventilatory parameter (peak inspiratory pressure (PIP)) [ Time Frame: up to 28 days ]
• Change from baseline in ventilatory parameter (plateau pressure (Pplat)) [ Time Frame: up to 28 days ]
• Change from baseline in blood gas analysis acid-base balance parameter (pCO2) [ Time Frame: up to 28 days ]
• Change from baseline in blood gas analysis acid-base balance parameter (pO2) [ Time Frame: up to 28 days ]
• Change from baseline in blood gas analysis acid-base balance parameter (HCO3) [ Time Frame: up to 28 days ]
• Change from baseline in blood gas analysis acid-base balance parameter (lactate) [ Time Frame: up to 28 days ]

Current Other Pre-specified Outcome Measures (submitted: August 3, 2021)

• Change from baseline in lowest and dynamic surface tensions (mN/m) from Tracheal Aspirate (TA) samples [ Time Frame: at 12, 24, 48, 72 and 96 hrs after start of treatment (first dose in the poractant alfa group) or after randomisation (in the control group) ]
  exploratory endpoint for UK patients only
• Change from baseline in concentrations of surfactant phospholipids (mg/ml) from TA samples [ Time Frame: at 12, 24, 48, 72 and 96 hrs after start of treatment (first dose in the poractant alfa group) or after randomisation (in the control group) ]
  exploratory endpoint for UK patients only
• Change from baseline in concentrations of proteins (ng/ml) from TA samples [ Time Frame: at 12, 24, 48, 72 and 96 hrs after start of treatment (first dose in the poractant alfa group) or after randomisation (in the control group) ]
  exploratory endpoint for UK patients only
• Change from baseline in inflammatory indices such as cellular and cytokine (pg/ml) inflammatory markers (e.g. IL-1, IL-6, TNF alpha, IFN gamma, and lymphocyte markers) from TA and blood samples [ Time Frame: at 12, 24, 48, 72 and 96 hrs after start of treatment (first dose in the poractant alfa group) or after randomisation (in the control group) ]
  exploratory endpoint for UK patients only

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Poractant Alfa - Curosurf and SARS-COV-19 ARDS (Covid-19)
• Official Title: Multicenter, Open-label, Randomised Trial to Assess the Efficacy and Tolerability of Poractant Alfa(Porcine Surfactant, Curosurf®) in Hospitalized Patients With SARS-COV-19 Acute Respiratory Distress Syndrome (ARDS)
• Brief Summary: The purpose of this Phase II -Proof of Concept study is to evaluate the efficacy and safety of poractant alfa (Curosurf®), administered by endotracheal (ET) instillation in adult hospitalized patients with SARS-COV-19 acute respiratory distress syndrome (ARDS)

Detailed Description

This is a multicentre, open-label, randomized phase II proof of concept study. The efficacy and safety of poractant alfa will be evaluated in terms of ventilatory free days during the 21 days after randomization, in adult patients with ARDS due to SARS-COV-19 infection.

Each patient randomized to the study treatment will receive three administrations of Curosurf ® with a 24 hours dosing interval.

The assessment collection will last until day 28 when the evaluation will occur at the ICU, or by phone call if the patient has been discharged before.

Seventy patients will be randomized in the study with a ratio 3:2 (i.e. 42 patients in the poractant alfa arm and 28 in the control arm).

The control arm population is treated as per Standard of Care (SoC).

This study will be conducted in UK, US and Italy.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Seventy patients will be randomized in the study with a ratio 3:2 (i.e. 42 patients in the poractant alfa arm and 28 in the control arm).

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Acute Respiratory Distress Syndrome

Intervention

Drug: CUROSURF® (poractant alfa)

Three administrations with a 24 hours dosing interval.

Each ET administration 1, 2, and 3 will consist of poractant alfa bolus:

30mg /kg (Lean Body Weight-LBW) = 0.375ml /kg LBW. Dilution with normal saline up to 2ml /kg LBW

Study Arms

• No Intervention: Control cohort

  Approximately 28 patients will be included in this main control cohort.

  The above-mentioned control cohort population will continue receiving the SoC

• Experimental: Poractant alfa treated cohort
  42 patients will be treated with CUROSURF® (poractant alfa).
  Intervention: Drug: CUROSURF® (poractant alfa)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 28, 2022): 22
• Original Estimated Enrollment (submitted: August 5, 2020): 85
• Actual Study Completion Date: March 18, 2022
• Actual Primary Completion Date: March 18, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Participants are eligible to be included in the study if the following criteria apply:

1. Male or female ≥18 and ≤ 80 years of age
2. Informed consent for participation in the study (refer to section 15 for detailed inform consent procedure)
3. Positive 2019-nCoV rt-PCR before randomisation
4. PaO2/FiO2 ratio < 150 mmHg
5. Lung compliance ≤45 ml/cmH20
6. Intubated and artificially ventilated less than 48 hours before the first poractant alfa administration

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

1. Any contraindications to surfactant administration e.g., pulmonary hemorrhage and pneumothorax)
2. Weight < 40kg
3. Stage 4 severe chronic kidney disease (i.e., eGFR < 30)
4. Pregnancy
5. Administration of any nebulized surfactant in the 48 hours before the first poractant alfa administration

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy, United Kingdom, United States

Administrative Information

• NCT Number: NCT04502433
• Other Study ID Numbers: CLI-050000-04; 2020-002632-75 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Chiesi Farmaceutici S.p.A.
• Study Sponsor: Chiesi Farmaceutici S.p.A.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Clark Howard, Prof. /MD; University College, London

• PRS Account: Chiesi Farmaceutici S.p.A.
• Verification Date: March 2022