A Phase 3 Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Intravenously Administered Ravulizumab Compared With Best Supportive Care in Patients With COVID-19 Severe Pneumonia, Acute Lung Injury, or Acute Respiratory Distress Syndrome

Alexion Pharmaceuticals, Inc.38 sites in 5 countries202 target enrollmentMay 10, 2020

ConditionsCOVID-19 Severe Pneumonia Acute Lung Injury Acute Respiratory Distress Syndrome Pneumonia, Viral

Overview

Phase: Phase 3
Intervention: Not specified
Conditions: COVID-19 Severe Pneumonia
Sponsor: Alexion Pharmaceuticals, Inc.
Enrollment: 202
Locations: 38
Primary Endpoint: Survival (Based On All-Cause Mortality) in Participants in the ITT Population At Day 29
Status: Terminated
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This study evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of ravulizumab administered in adult participants with coronavirus disease 2019 (COVID-19) severe pneumonia, acute lung injury, or acute respiratory distress syndrome. Participants were randomly assigned to receive ravulizumab in addition to best supportive care (BSC) (2/3 of the participants) or BSC alone (1/3 of the participants). BSC consisted of medical treatment and/or medical interventions per routine hospital practice.

Registry

clinicaltrials.gov

Start Date

May 10, 2020

End Date

April 8, 2021

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Alexion Pharmaceuticals, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Males or female participants ≥ 18 years of age and ≥ 40 kilograms at the time of providing informed consent.
•Confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 infection (for example, via polymerase chain reaction and/or antibody test) presenting as severe COVID-19 requiring hospitalization.
•Severe pneumonia, acute lung injury, or acute respiratory distress syndrome confirmed by computed tomography or X-ray at Screening or within the 3 days prior to Screening, as part of the participant's routine clinical care.
•Respiratory distress requiring mechanical ventilation, which can be either invasive (requiring endotracheal intubation) or noninvasive (with continuous positive airway pressure or bilevel positive airway pressure).
•Female participants of childbearing potential and male participants with female partners of childbearing potential must follow protocol specified contraception guidance for avoiding pregnancy for 8 months after treatment with the study drug.

Exclusion Criteria

•Participant was not expected to survive for more than 24 hours.
•Participant was on invasive mechanical ventilation with intubation for more than 48 hours prior to Screening.
•Severe pre-existing cardiac disease (that is, New York Heart Association Class 3 or Class 4, acute coronary syndrome or persistent ventricular tachyarrhythmias).
•Participant had an unresolved Neisseria meningitidis infection.
•Used the following medications and therapies:
•Current treatment with a complement inhibitor or
•Intravenous immunoglobulin within 4 weeks prior to randomization on Day 1
•Treatment with investigational therapy in a clinical study within 30 days before randomization, or within 5 half-lives of that investigational therapy, whichever was greater. Exceptions:
•Investigational therapies were allowed if received as part of BSC through an expanded access protocol or emergency approval for the treatment of COVID-
•Investigational antiviral therapies (such as remdesivir) were allowed even if received as part of a clinical study.

Outcomes

Primary Outcomes

Survival (Based On All-Cause Mortality) in Participants in the ITT Population At Day 29

Time Frame: Day 29

Survival (based on all-cause mortality) in Participants in the ITT Population at Day 29 was analyzed. The result for the survival was estimated survival combined over all imputations.

Secondary Outcomes

Number Of Days Free Of Mechanical Ventilation At Day 29(Day 29)
Change From Baseline In Peripheral Capillary Oxygen Saturation/Fraction Of Inspired Oxygen (SpO2/FiO2) At Day 29(Baseline, Day 29)
Number of Days the Participants Were Alive and Not in the Hospital(Day 1 through Day 29)
Estimated Number of Participants Alive At Up To Day 60 and At Up To Day 90(Up to Day 60 and Up to Day 90)
Number of Days the Participants Were Alive and Not in ICU(Day 1 through Day 29)
Change From Baseline In Sequential Organ Failure Assessment (SOFA) At Day 29(Baseline, Day 29)
Serum Ravulizumab Concentrations Prior to Dosing on Day 1 and Day 29(Day 1 and Day 29)
Change From Baseline In Terminal Complement Complex C5b-9 At Day 29(Baseline, Day 29)
Change From Baseline In Serum Free Complement Component 5 Concentrations At Day 29(Baseline, Day 29)