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

NCT ID: NCT04369469

Last Updated: 2022-05-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 202 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-10
• Study Completion Date: 2021-04-08

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1 - Ravulizumab + BSC

Group Type: EXPERIMENTAL

Ravulizumab

Intervention Type: BIOLOGICAL

Weight-based doses of ravulizumab were administered intravenously on Days 1, 5, 10, and 15.

BSC

Intervention Type: OTHER

Participants received medications, therapies, and interventions per standard hospital treatment protocols.

Group 2 - BSC alone

Group Type: OTHER

BSC

Intervention Type: OTHER

Participants received medications, therapies, and interventions per standard hospital treatment protocols.

Interventions

Ravulizumab

Weight-based doses of ravulizumab were administered intravenously on Days 1, 5, 10, and 15.

Intervention Type: BIOLOGICAL

BSC

Participants received medications, therapies, and interventions per standard hospital treatment protocols.

Intervention Type: OTHER

Other Intervention Names

Ultomiris; ALXN1210

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Central Arkansas Veterans Healthcare System

Little Rock, Arkansas, United States

LAC/USC Health Center

Los Angeles, California, United States

UC Irvine Medical Center

Orange, California, United States

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

University of Florida

Jacksonville, Florida, United States

Mayo Clinic Florida

Jacksonville, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

Norton Healthcare

Louisville, Kentucky, United States

Baltimore VA Medical Center

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Boston Medical Center

Boston, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

Mayo Clinic Health System

Mankato, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

NYU Langone Health Center

New York, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Westchester Medical Center

Valhalla, New York, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Baptist Memorial Hospital

Memphis, Tennessee, United States

Houston Methodist Hospital

Houston, Texas, United States

Mayo Clinic Health System in Eau Claire

Eau Claire, Wisconsin, United States

Mayo Clinic Health System

La Crosse, Wisconsin, United States

Hôpital Raymond Poincaré

Garches, Hauts De Seine, France

Hôpital Henri Mondor

Créteil, Val De Marne, France

Hôpital Bicêtre

Le Kremlin-Bicêtre, Val De Marne, France

Jikei University Hospital

Minato-Ku, Tokyo, Japan

Tokyo Medical University Hospital

Shinjuku-Ku, Tokyo, Japan

Medical Hospital, Tokyo Medical and Dental University

Bunkyō City, Tokyo-To, Japan

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

King's College Hospital

London, Greater London, United Kingdom

Hammersmith Hospital

London, Greater London, United Kingdom

Royal Liverpool University Hospital

Liverpool, Merseyside, United Kingdom

Queen Elizabeth Hospital

Birmingham, West Midlands, United Kingdom

St James's University Hospital

Leeds, West Yorkshire, United Kingdom

Countries

United States; France; Japan; Spain; United Kingdom

References

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

Reference Type: BACKGROUND

McEneny-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.

Reference Type: RESULT

PMID: 33826106 (View on PubMed)

Smith 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.

Reference Type: RESULT

PMID: 32660611 (View on PubMed)

Annane 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.

Reference Type: DERIVED

PMID: 36958364 (View on PubMed)

Kreuzberger 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.

Reference Type: DERIVED

PMID: 34473343 (View on PubMed)

Java 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.

Reference Type: DERIVED

PMID: 32554923 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ALXN1210-COV-305

Identifier Type: -

Identifier Source: org_study_id