Astegolimab or Efmarodocokin Alfa in Patients With Severe COVID-19 Pneumonia: A Randomized, Phase 2 Trial*

Critical Care Medicine - Tập 51 Số 1 - Trang 103-116 - 2023
Michael R. Waters1, James A. McKinnell2,3, André C. Kalil4, Greg S. Martin5, Timothy G. Buchman6, Wiebke Theess7, Xiaoying Yang8, Annemarie Lekkerkerker9, Tracy Staton9, Carrie M. Rosenberger10, Rajita Pappu11, Yehong Wang12,2, Wenhui Zhang12,2, Logan Brooks12,2, Dorothy Cheung7, Joshua Galanter3,13, Hubert Chen7, Divya Mohan7, Melicent C. Peck7
1Velocity Clinical Research, Chula Vista, CA.
2David Geffen School of Medicine, Harbor-UCLA Medical Center, Torrance, CA.
3Milefchik-Rand Medical Group, Torrance Memorial Medical Center, Torrance, CA.
4Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE
5Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, and Grady Health System, Atlanta, GA.
6Department of Surgery, Emory University School of Medicine, Atlanta, GA
7Early Clinical Development, Genentech, Inc., South San Francisco, CA.
8Product Development Data Sciences, Genentech, Inc., South San Francisco, CA.
9Biomarker Development, Genentech, Inc., South San Francisco, CA.
10Biomarker Discovery, Genentech, Inc., South San Francisco, CA.
11Immunology Discovery, Genentech, Inc., South San Francisco, CA.
12Clinical Pharmacology, Genentech, Inc., South San Francisco, CA.
13Product Development Safety, Genentech, Inc., South San Francisco, CA.

Tóm tắt

OBJECTIVES: Severe cases of COVID-19 pneumonia can lead to acute respiratory distress syndrome (ARDS). Release of interleukin (IL)-33, an epithelial-derived alarmin, and IL-33/ST2 pathway activation are linked with ARDS development in other viral infections. IL-22, a cytokine that modulates innate immunity through multiple regenerative and protective mechanisms in lung epithelial cells, is reduced in patients with ARDS. This study aimed to evaluate safety and efficacy of astegolimab, a human immunoglobulin G2 monoclonal antibody that selectively inhibits the IL-33 receptor, ST2, or efmarodocokin alfa, a human IL-22 fusion protein that activates IL-22 signaling, for treatment of severe COVID-19 pneumonia. DESIGN: Phase 2, double-blind, placebo-controlled study (COVID-astegolimab-IL). SETTING: Hospitals. PATIENTS: Hospitalized adults with severe COVID-19 pneumonia. INTERVENTIONS: Patients were randomized to receive IV astegolimab, efmarodocokin alfa, or placebo, plus standard of care. The primary endpoint was time to recovery, defined as time to a score of 1 or 2 on a 7-category ordinal scale by day 28. MEASUREMENTS AND MAIN RESULTS: The study randomized 396 patients. Median time to recovery was 11 days (hazard ratio [HR], 1.01 d; p = 0.93) and 10 days (HR, 1.15 d; p = 0.38) for astegolimab and efmarodocokin alfa, respectively, versus 10 days for placebo. Key secondary endpoints (improved recovery, mortality, or prevention of worsening) showed no treatment benefits. No new safety signals were observed and adverse events were similar across treatment arms. Biomarkers demonstrated that both drugs were pharmacologically active. CONCLUSIONS: Treatment with astegolimab or efmarodocokin alfa did not improve time to recovery in patients with severe COVID-19 pneumonia.

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Critical Care Medicine

Tập 51 Số 1

103-116

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