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A randomized double-blind placebo-controlled trial of intravenous plasma-purified alpha-1 antitrypsin for severe COVID-19 illness.

Trial Profile

A randomized double-blind placebo-controlled trial of intravenous plasma-purified alpha-1 antitrypsin for severe COVID-19 illness.

Status: Recruiting
Phase of Trial: Phase II

Latest Information Update: 28 Apr 2020

At a glance

  • Drugs Alpha 1-antitrypsin (Primary)
  • Indications COVID 2019 infections; Respiratory distress syndrome
  • Focus Adverse reactions
  • Most Recent Events

    • 26 Apr 2020 Status changed from planning to recruiting.
    • 30 Mar 2020 New trial record
    • 25 Mar 2020 According to a Grifols media release, the company will is collaborating with certain hospitals in the design of this study.

Trial Overview

Purpose

The aim of the study is to conduct a clinical trial of IV AAT as a prospective anti-inflammatory therapy for severely ill COVID-19 patients with ARDS requiring ICU admission. The primary objective is to demonstrate a biological effect of IV Prolastin administered weekly at 120mg per kilogram of ideal body weight in patients with severe COVID-19 illness requiring intubation and mechanical ventilation for ARDS by reducing circulating levels of IL-6 as measured by plasma ELISA. The study sample size is sufficient to demonstrate a significant difference in patients receiving Prolastin versus patients receiving placebo.

Primary Endpoints

The primary effectiveness outcome measure, a continuous variable, is IL-6 in plasma as measured by ELISA.

Timepoint: day 2 , day 7, day 14, day 21 and day 28

Other Endpoints

Safety and tolerability of IMP in the respective groups, as defined by the number of SEAs and AEs, binary variable
• PaO2/FiO2 ratio, continuous variable
• Respiratory compliance, continuous variable
• Sequential organ failure assessment (SOFA) score, continuous variable
• Mortality, binary variable
• Time on ventilator in days, continuous variable
• Circulating AAT levels as measured by nephelometry, continuous variable
• Plasma levels of IL-1β as measured by ELISA, continuous variable
• Plasma levels of IL-8 as measured by ELISA, continuous variable
• Plasma levels of IL-10 as measured by ELISA, continuous variable
• Plasma levels levels of soluble TNF receptor 1 (sTNFR1, a surrogate marker for TNF-α) as measured by ELISA, continuous variable
• Development of shock, defined for the purpose of this study as life-threatening organ dysfunction caused by a dysregulated response to infection, with critical reduction in tissue perfusion and acute failure of multiple organs, including the lungs, kidneys, and liver, binary variable
• Acute kidney injury defined as an abrupt sustained rise in urea and creatinine, binary variable
• Need for renal replacement therapy, binary variable
• Clinical relapse, as defined by the need for readmission to the ICU or a marked decline in PaO2/FiO2 or development of shock or mortality following a period of sustained clinical improvement, binary variable
• Secondary bacterial pneumonia as defined by the combination of radiographic findings and sputum/airway secretion microscopy and culture, binary variable
Timepoint: day 2 , day 7, day 14, day 21 and day 28 [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -
Respiratory distress syndrome treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 36

  • Sex male & female
  • Age Group ≥ 18 years; adult; elderly

Patient Inclusion Criteria

1. Laboratory-confirmed diagnosis of COVID-19 infection2. Moderate to severe ARDS with a PaO2/FiO2 ratio <200 and a requirement for vasopressors (0.05-0.1μg/kg/min)3. >18 years of age

Patient Exclusion Criteria

1. Not receiving invasive mechanical ventilation2. More than 96 hours from the onset of ARDS3. Age < 18 years4. Known to be pregnant or breastfeeding5. Participation in a clinical trial of an investigational medicinal product within 30 days6. Major trauma in the prior 5 days7. Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last year8. WHO Class III or IV pulmonary hypertension9. Pulmonary embolism within past 3 months10. Currently receiving extracorporeal life support (ECLS)11. Currently receiving renal replacement therapy12. Severe chronic liver disease with Child-Pugh score > 1213. DNAR (Do Not Attempt Resuscitation) order in place14. Treatment withdrawal imminent within 24 hours15. Prisoners16. Non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available.17. Enrolled in a concomitant clinical trial of a medicinal product18. IgA deficiency19. AAT phenotype other than Pi*MM as assessed by isoelectric focusing of plasma

Trial Details

Identifiers

Identifier Owner
EudraCT2020-001391-15 European Clinical Trials Database
V1Mar2020 -

Organisations

  • Affiliations Grifols

Trial Dates

  • Initiation Dates

    Actual : 24 Apr 2020

  • End Dates

    Planned : 24 Aug 2020

Other Details

  • Design double-blind; parallel; prospective; randomised
  • Phase of Trial Phase II
  • Location Ireland
  • Focus Adverse reactions

Interventions

Drugs Route Formulation
Alpha 1-antitrypsinPrimary Drug Intravenous Infusion

INN-Proposed INN: HUMAN ALPHA1-PROTEINASE INHIBITOR
Investigational Medicinal Product Trade Name: Prolastin
Name of the Marketing Authorisation Holder: Grifols Deutschland GmbH
Country which granted the Marketing Authorisation: Germany
Pharmaceutical Form: Powder and solvent for solution for infusion
IMP Routes of Administration: Intravenous use
Active Substance CAS number: 9041-92-3
Active Substance other descriptive name: HUMAN ALPHA1-PROTEINASE INHIBITOR
EV Substance code: SUB130886
Active Substance INN: HUMAN ALPHA1-PROTEINASE INHIBITOR
Chemical Origin Active Substance: yes

Number Of treatment arms In the trial: 3

Is placebo used in this trial?: yes

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Mandy Jackson
RCSI Smurfit Building
dublin
Postcode: county dub
Ireland
Telephone: +353852147569
mandyjackson@Rcsi.ie
show details
Royal College of Surgeons Ireland Ireland

Centres

Centre Name Location Trial Centre Country
Royal College of Surgeons Ireland Dublin Ireland

Trial History

Event Date Event Type Comment
28 Apr 2020 Other trial event New source identified and integrated European Clinical Trials Database (EudraCT2020-001391-15). Updated 28 Apr 2020
26 Apr 2020 Status change - recruiting Status changed from planning to recruiting. Updated 28 Apr 2020
30 Mar 2020 New trial record New trial record Updated 30 Mar 2020
25 Mar 2020 Other trial event According to a Grifols media release, the company will is collaborating with certain hospitals in the design of this study. Updated 30 Mar 2020

References

  1. European Clinical Trials Database. Trial-Reg 2016;.

    Available from: URL: https://www.clinicaltrialsregister.eu
  2. Grifols. Grifols Announces Formal Collaboration with US Government to Produce the First Treatment Specifically Targeting COVID-19. Media-Rel 2020;.

    Media Release
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