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

• ClinicalTrials.gov Identifier: NCT04502433
• Recruitment Status: Recruiting
• First Posted: August 6, 2020
• Last Update Posted: January 20, 2021
• 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: January 20, 2021
• Actual Study Start Date: January 6, 2021
• Estimated Primary Completion Date: July 31, 2021 (Final data collection date for primary outcome measure)

Current 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.

• Original Primary Outcome Measures: Same as current

Current 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 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• 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 UK 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.

The same evaluation is planned in a separate cohort of patients under extracorporeal membrane oxygenation (vvECMO) in terms of ECMO free days during the 21 days after randomization.

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). An additional exploratory cohort of 15 patients in ECMO will be randomised by 3 sites with a ratio 3:2 (i.e. 9 patients in the poractant alfa arm and 6 in the control arm).

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

• 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). An additional exploratory cohort of 15 patients in ECMO will be randomized by 3 sites with a ratio 3:2 (i.e. 9 patients in the poractant alfa arm and 6 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. An additional exploratory cohort of 6 patients in ECMO will be enrolled by 3 sites. 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). An additional exploratory cohort of 9 patients in ECMO will be randomised by 3 sites and treated with the poractant alfa
  Intervention: Drug: CUROSURF® (poractant alfa)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 5, 2020): 85
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 31, 2021
• Estimated Primary Completion Date: July 31, 2021 (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

   Additional inclusion criterion for ECMO-cohort:

7. Supported with vvECMO less than 48 hours before the first poractant alfa administration - for the ECMO-cohort substudy cohort only

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
6. Extracorporeal membrane oxygenation* * [Exclusion criterion NOT applicable for patients eligible for the ECMO-cohort]

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Chiesi Clinical trial Info; +39 0521 2791; clinicaltrials_info@chiesi.com

• Listed Location Countries: United Kingdom

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

• IPD Sharing Statement: Not Provided
• 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: January 2021