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

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.

Timeline

Start

2020-05-10

Primary completion

2021-02-08

Completion

2021-04-08

Outcome

Missed primary endpoint

Stopped: “Met futility bar at interim analysis”

registry analysis (other test); Group 1 - Ravulizumab + BSC vs Group 2 - BSC Alone; p = 0.6059; Risk Difference (RD) -0.0205 (95% CI -0.1703 to 0.1293); NCT04369469 ↗

paper INTERPRETATION: Addition of ravulizumab to BSC did not improve survival or other secondary outcomes. PMID 36958364 ↗

Publications

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

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Ravulizumab	Monoclonal antibody	600 mg	Intravenous
Subject	Ravulizumab	Monoclonal antibody	900 mg	Intravenous
Subject	Ravulizumab	Monoclonal antibody	2400 mg	Intravenous
Subject	Ravulizumab	Monoclonal antibody	2700 mg	Intravenous
Subject	Ravulizumab	Monoclonal antibody	3000 mg	Intravenous

Indications