Study Stopped
Met futility bar at interim analysis
Efficacy and Safety Study of IV Ravulizumab in Patients With COVID-19 Severe Pneumonia
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
1 other identifier
interventional
202
5 countries
39
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started May 2020
Shorter than P25 for phase_3
39 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 28, 2020
CompletedFirst Posted
Study publicly available on registry
April 30, 2020
CompletedStudy Start
First participant enrolled
May 10, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 8, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
April 8, 2021
CompletedResults Posted
Study results publicly available
May 24, 2022
CompletedMay 24, 2022
May 1, 2022
9 months
April 28, 2020
February 15, 2022
May 4, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Survival (Based On All-Cause Mortality) in Participants in the ITT Population At 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.
Day 29
Secondary Outcomes (9)
Number Of Days Free Of Mechanical Ventilation At Day 29
Day 29
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
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
- +4 more secondary outcomes
Study Arms (2)
Group 1 - Ravulizumab + BSC
EXPERIMENTALGroup 2 - BSC alone
OTHERInterventions
Weight-based doses of ravulizumab were administered intravenously on Days 1, 5, 10, and 15.
Participants received medications, therapies, and interventions per standard hospital treatment protocols.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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-19.
- Investigational antiviral therapies (such as remdesivir) were allowed even if received as part of a clinical study.
- Female participants who were breastfeeding or who have a positive pregnancy test result at Screening.
- History of hypersensitivity to any ingredient contained in the study drug, including hypersensitivity to murine proteins.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (39)
Central Arkansas Veterans Healthcare System
Little Rock, Arkansas, 72205, United States
LAC/USC Health Center
Los Angeles, California, 90033, United States
UC Irvine Medical Center
Orange, California, 92868, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
University of Florida
Jacksonville, Florida, 32209, United States
Mayo Clinic Florida
Jacksonville, Florida, 32224, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Norton Healthcare
Louisville, Kentucky, 40241, United States
Baltimore VA Medical Center
Baltimore, Maryland, 21201, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Boston Medical Center
Boston, Massachusetts, 02118, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Mayo Clinic Health System
Mankato, Minnesota, 56001, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
NYU Langone Health Center
New York, New York, 10016, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
Westchester Medical Center
Valhalla, New York, 10595, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Baptist Memorial Hospital
Memphis, Tennessee, 38120, United States
Houston Methodist Hospital
Houston, Texas, 77030, United States
Mayo Clinic Health System in Eau Claire
Eau Claire, Wisconsin, 54703, United States
Mayo Clinic Health System
La Crosse, Wisconsin, 54601, United States
Hôpital Raymond Poincaré
Garches, Hauts De Seine, 92380, France
Hôpital Henri Mondor
Créteil, Val De Marne, 94000, France
Hôpital Bicêtre
Le Kremlin-Bicêtre, Val De Marne, 94275, France
Jikei University Hospital
Minato-Ku, Tokyo, 105-8471, Japan
Tokyo Medical University Hospital
Shinjuku-Ku, Tokyo, 160-0023, Japan
Medical Hospital, Tokyo Medical and Dental University
Bunkyō City, Tokyo-To, 113-8519, Japan
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907, Spain
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
Hospital Universitario Ramon y Cajal
Madrid, 28034, Spain
King's College Hospital
London, Greater London, SE5 9RS, United Kingdom
Hammersmith Hospital
London, Greater London, W12 0HS, United Kingdom
Royal Liverpool University Hospital
Liverpool, Merseyside, L7 8XP, United Kingdom
Queen Elizabeth Hospital
Birmingham, West Midlands, B15 2TH, United Kingdom
St James's University Hospital
Leeds, West Yorkshire, LS9 7TF, United Kingdom
Related Publications (6)
WHO. Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected. Interim guidance, 28 January 2020.
BACKGROUNDMcEneny-King AC, Monteleone JPR, Kazani SD, Ortiz SR. Pharmacokinetic and Pharmacodynamic Evaluation of Ravulizumab in Adults with Severe Coronavirus Disease 2019. Infect Dis Ther. 2021 Jun;10(2):1045-1054. doi: 10.1007/s40121-021-00425-7. Epub 2021 Apr 7.
PMID: 33826106RESULTSmith K, Pace A, Ortiz S, Kazani S, Rottinghaus S. 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: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jul 13;21(1):639. doi: 10.1186/s13063-020-04548-z.
PMID: 32660611RESULTAnnane D, Pittock SJ, Kulkarni HS, Pickering BW, Khoshnevis MR, Siegel JL, Powell CA, Castro P, Fujii T, Dunn D, Smith K, Mitter S, Kazani S, Kulasekararaj A. Intravenous ravulizumab in mechanically ventilated patients hospitalised with severe COVID-19: a phase 3, multicentre, open-label, randomised controlled trial. Lancet Respir Med. 2023 Dec;11(12):1051-1063. doi: 10.1016/S2213-2600(23)00082-6. Epub 2023 Mar 20.
PMID: 36958364DERIVEDKreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
PMID: 34473343DERIVEDJava A, Apicelli AJ, Liszewski MK, Coler-Reilly A, Atkinson JP, Kim AH, Kulkarni HS. The complement system in COVID-19: friend and foe? JCI Insight. 2020 Aug 6;5(15):e140711. doi: 10.1172/jci.insight.140711.
PMID: 32554923DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
Enrollment of participants was paused on 13-Jan-2021. At that time, 202 participants had been randomized. An interim analysis for efficacy and futility was conducted on data from the first 122 participants who completed the Primary Evaluation Period. The analysis showed that the study met the prespecified stopping criteria for futility. After review of all participant data, Alexion terminated the study on 01-Sep-2021.
Results Point of Contact
- Title
- Alexion Pharmaceuticals, Inc.
- Organization
- Alexion Pharmaceuticals, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 28, 2020
First Posted
April 30, 2020
Study Start
May 10, 2020
Primary Completion
February 8, 2021
Study Completion
April 8, 2021
Last Updated
May 24, 2022
Results First Posted
May 24, 2022
Record last verified: 2022-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, CSR
Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.