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Efficacy and Safety Study of IV Ravulizumab in Patients With COVID-19 Severe Pneumonia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04369469
Recruitment Status : Terminated (Met futility bar at interim analysis)
First Posted : April 30, 2020
Results First Posted : May 24, 2022
Last Update Posted : May 24, 2022
Sponsor:
Information provided by (Responsible Party):
Alexion

Study Description
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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.

Condition or disease Intervention/treatment Phase
COVID-19 Severe Pneumonia Acute Lung Injury Acute Respiratory Distress Syndrome Pneumonia, Viral Biological: Ravulizumab Other: BSC Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 202 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 10, 2020
Actual Primary Completion Date : February 8, 2021
Actual Study Completion Date : April 8, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Ravulizumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Group 1 - Ravulizumab + BSC Biological: Ravulizumab
Weight-based doses of ravulizumab were administered intravenously on Days 1, 5, 10, and 15.
Other Names:
  • Ultomiris
  • ALXN1210

Other: BSC
Participants received medications, therapies, and interventions per standard hospital treatment protocols.
Group 2 - BSC alone Other: BSC
Participants received medications, therapies, and interventions per standard hospital treatment protocols.


Outcome Measures
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Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Number Of Days Free Of Mechanical Ventilation At Day 29 [ Time Frame: Day 29 ]
    The number of days free of mechanical ventilation was defined as the total number of days from Day 1 to Day 29 without invasive or non-invasive mechanical ventilation.

  2. Number of Days the Participants Were Alive and Not in ICU [ Time Frame: Day 1 through Day 29 ]
    The number of days that the participants were alive and not in the ICU from Day 1 through Day 29 are presented.

  3. Change From Baseline In Sequential Organ Failure Assessment (SOFA) At Day 29 [ Time Frame: Baseline, Day 29 ]
    Baseline was defined as the last available assessment on or before Day 1 for all participants. Participants were evaluated using the SOFA score, an assessment tool that included a review of 6 organ systems: respiratory, renal, hepatic, cardiac, coagulation, and central nervous system. Each organ system was scored from 0 to 4 points using the worst value observed within the previous 24 hours. The total score ranged from 0 to 24, with a higher score indicating a worse condition.

  4. Change From Baseline In Peripheral Capillary Oxygen Saturation/Fraction Of Inspired Oxygen (SpO2/FiO2) At Day 29 [ Time Frame: Baseline, Day 29 ]
    Oxygenation was measured using the SpO2 and the amount of supplemental oxygen as measured by the FiO2 received by taking the ratio of these 2 measures at the same time point.

  5. Number of Days the Participants Were Alive and Not in the Hospital [ Time Frame: Day 1 through Day 29 ]
    The number of days that the participants were alive and not in the hospital from Day 1 through Day 29 are presented.

  6. Estimated Number of Participants Alive At Up To Day 60 and At Up To Day 90 [ Time Frame: Up to Day 60 and Up to Day 90 ]
    For this analysis, 2 participants in Group 1 (Ravulizumab + BSC) and 1 participant in Group 2 (BSC Alone) were censored at Day 90. The estimated number of participants alive for this analysis was calculated using the method of Kaplan and Meier (KM) and compared using a log-rank test stratified by intubated or not intubated on Day 1 as a sensitivity analysis. This Outcome Measure was designed to project an estimate of how many participants would be alive and not the actual number of alive participants. All-Cause Mortality data is provided in the Adverse Events Section.

  7. Serum Ravulizumab Concentrations Prior to Dosing on Day 1 and Day 29 [ Time Frame: Day 1 and Day 29 ]
    Results are reported in micrograms/milliliter (μg/mL).

  8. Change From Baseline In Serum Free Complement Component 5 Concentrations At Day 29 [ Time Frame: Baseline, Day 29 ]
  9. Change From Baseline In Terminal Complement Complex C5b-9 At Day 29 [ Time Frame: Baseline, Day 29 ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or female participants ≥ 18 years of age and ≥ 40 kilograms at the time of providing informed consent.
  2. 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.
  3. 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.
  4. 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).
  5. 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:

  1. Participant was not expected to survive for more than 24 hours.
  2. Participant was on invasive mechanical ventilation with intubation for more than 48 hours prior to Screening.
  3. Severe pre-existing cardiac disease (that is, New York Heart Association Class 3 or Class 4, acute coronary syndrome or persistent ventricular tachyarrhythmias).
  4. Participant had an unresolved Neisseria meningitidis infection.

  5. Used the following medications and therapies:

    • Current treatment with a complement inhibitor or
    • Intravenous immunoglobulin within 4 weeks prior to randomization on Day 1

  6. 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-19.
    • Investigational antiviral therapies (such as remdesivir) were allowed even if received as part of a clinical study.
  7. Female participants who were breastfeeding or who have a positive pregnancy test result at Screening.
  8. History of hypersensitivity to any ingredient contained in the study drug, including hypersensitivity to murine proteins.
  9. Participant who was not currently vaccinated against Neisseria meningitidis, unless the participant agrees to receive prophylactic treatment with appropriate antibiotics for at least 8 months after the last infusion of study drug or until at least 2 weeks after the participant receives vaccination against Neisseria meningitidis.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04369469


Locations
Show Show 39 study locations
Sponsors and Collaborators
Alexion
  Study Documents (Full-Text)

Documents provided by Alexion:
Study Protocol  [PDF] June 9, 2020
Statistical Analysis Plan  [PDF] July 31, 2020

More Information
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Publications of Results:

Other Publications:
WHO. Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected. Interim guidance, 28 January 2020.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Alexion
ClinicalTrials.gov Identifier: NCT04369469    
Other Study ID Numbers: ALXN1210-COV-305
First Posted: April 30, 2020    Key Record Dates
Results First Posted: May 24, 2022
Last Update Posted: May 24, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.
Supporting Materials: Study Protocol
Clinical Study Report (CSR)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alexion:
acute lung injury
acute respiratory distress syndrome
antibodies, monoclonal, humanized
COVID-19
hospitalization
pneumonia
severe pneumonia
 severe acute respiratory syndrome
severe acute respiratory syndrome coronavirus 2
randomized controlled study
ravulizumab
respiratory distress syndrome, adult
Ultomiris
viral
Additional relevant MeSH terms:
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COVID-19
Pneumonia
Pneumonia, Viral
Respiratory Distress Syndrome
Respiratory Distress Syndrome, Newborn
Acute Lung Injury
Lung Injury
Syndrome
Disease
Pathologic Processes
Respiratory Tract Infections
Infections
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
 Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Wounds and Injuries
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Thoracic Injuries
Ravulizumab
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs