REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19.

Adult Antibodies, Monoclonal, Humanized / adverse effects Antibodies, Neutralizing / adverse effects COVID-19 / diagnosis Double-Blind Method Drug Combinations Female Humans Immunologic Factors / adverse effects Least-Squares Analysis Male Middle Aged Outpatients Reverse Transcriptase Polymerase Chain Reaction SARS-CoV-2 / genetics Viral Load / drug effects COVID-19 Drug Treatment

Journal

The New England journal of medicine

ISSN: 1533-4406

Titre abrégé: N Engl J Med

Pays: United States

ID NLM: 0255562

Informations de publication

Date de publication:
21 01 2021

Historique:

pubmed: 18 12 2020

medline: 4 2 2021

entrez: 17 12 2020

Statut: ppublish

Résumé

Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads. In this ongoing, double-blind, phase 1-3 trial involving nonhospitalized patients with Covid-19, we investigated two fully human, neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, used in a combined cocktail (REGN-COV2) to reduce the risk of the emergence of treatment-resistant mutant virus. Patients were randomly assigned (1:1:1) to receive placebo, 2.4 g of REGN-COV2, or 8.0 g of REGN-COV2 and were prospectively characterized at baseline for endogenous immune response against SARS-CoV-2 (serum antibody-positive or serum antibody-negative). Key end points included the time-weighted average change in viral load from baseline (day 1) through day 7 and the percentage of patients with at least one Covid-19-related medically attended visit through day 29. Safety was assessed in all patients. Data from 275 patients are reported. The least-squares mean difference (combined REGN-COV2 dose groups vs. placebo group) in the time-weighted average change in viral load from day 1 through day 7 was -0.56 log In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group. (Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.).

Sections du résumé

BACKGROUND

Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads.

METHODS

In this ongoing, double-blind, phase 1-3 trial involving nonhospitalized patients with Covid-19, we investigated two fully human, neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, used in a combined cocktail (REGN-COV2) to reduce the risk of the emergence of treatment-resistant mutant virus. Patients were randomly assigned (1:1:1) to receive placebo, 2.4 g of REGN-COV2, or 8.0 g of REGN-COV2 and were prospectively characterized at baseline for endogenous immune response against SARS-CoV-2 (serum antibody-positive or serum antibody-negative). Key end points included the time-weighted average change in viral load from baseline (day 1) through day 7 and the percentage of patients with at least one Covid-19-related medically attended visit through day 29. Safety was assessed in all patients.

RESULTS

Data from 275 patients are reported. The least-squares mean difference (combined REGN-COV2 dose groups vs. placebo group) in the time-weighted average change in viral load from day 1 through day 7 was -0.56 log

CONCLUSIONS

In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group. (Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.).

Identifiants

DOI: 10.1056/NEJMoa2035002 PMID: 33332778 PMC: PMC7781102

pubmed: 33332778

doi: 10.1056/NEJMoa2035002

pmc: PMC7781102

doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0

Antibodies, Neutralizing 0

Drug Combinations 0

Immunologic Factors 0

casirivimab and imdevimab drug combination 0

Banques de données

ClinicalTrials.gov

['NCT04425629']

Types de publication

Clinical Trial, Phase I Clinical Trial, Phase II Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

238-251

Subventions

Organisme : U.S. Department of Health and Human Services

ID : HHSO100201700020C

Pays : International

Investigateurs

Dario Altamirano (D)

Ximena Graber (X)

Dickson Ellington (D)

Anita Kohli (A)

Vicki McIntyre (V)

Yessica Sachdeva (Y)

Mezgebe Berhe (M)

Haley Clinton (H)

Uriel Sandkovsky (U)

Emma Dishner (E)

Rahaf Al Masri (R)

Erin Duhaime (E)

Robinson Koilpillai (R)

Stephanie Cassady (S)

Jennifer Cox (J)

Eduardo Torres (E)

Faisal A Fakih Faisal (FA)

M Fakih (M)

Fernando Alvarado (F)

Daniel Layish (D)

Jose Diaz (J)

Augusto Focil (A)

Griselda Rosas (G)

Stevan Correa (S)

Michael Bogseth (M)

Roxana Stoici (R)

Gualberto Perez (G)

Joseph Pica (J)

Enrique Villareal (E)

Suraj Saggar (S)

Thomas Birch (T)

Benjamin De La Rosa (B)

Karyna Neyra (K)

Erina Kunwar (E)

Jeffrey Kingsley (J)

April Pixler (A)

Eric Meissner (E)

Andrew Goodwin (A)

Deeksha Jandhyala (D)

Nandita Nadig (N)

Godson Oguchi (G)

DeAndrea Duffus (D)

Moti Ramgopal (M)

Brenda Jacobs (B)

Lisa Cason (L)

Angela Trodglen (A)

Terence Chang (T)

Robbyn Traylor (R)

Lenee Gordon (L)

John McDivitt (J)

Jennifer Killion (J)

Rupal Amin (R)

Shauna Basener (S)

Timothy Lowry (T)

Kevin Cannon (K)

Mesha Chadwick (M)

Jazila Mantis (J)

Margaret Kemeny (M)

Merjona Saliaj (M)

Edward Cordasco (E)

Brian Zeno (B)

Heather Holmes (H)

Manuel Gordillo (M)

Rishi Bhattacharyya (R)

Sudha Tallapragada (S)

Annette Artau (A)

Julie Larkin (J)

Roberto Mercado (R)

Michael Milam (M)

Natan Kraitman (N)

Sarah Temple (S)

Lenka Offner (L)

Rabih Loutfi (R)

Kirk Voelker (K)

Michael Lowry (M)

Carl Dukes (C)

Robert Bass (R)

Larry Lothringer (L)

Leonel Reyes (L)

Adil Fatakia (A)

Marissa Miller (M)

Kristen Clinton (K)

Gary Reiss (G)

David Diemert (D)

Afsoon Roberts (A)

David Parenti (D)

Hana Akselrod (H)

Marc Siegel (M)

Andrew Meltzer (A)

Elissa Malkin (E)

Julie Philley (J)

Megan Devine (M)

Richard Yates (R)

Steven Hickerson (S)

Olayemi Osiyemi (O)

Jose A Menajovsky-Chaves (JA)

Christina Campbell (C)

Gerard Acloque (G)

Agustin Martinez (A)

Thomas Campbell (T)

Martin Krsak (M)

Steven Johnson (S)

Hillary Dunlevy (H)

Joseph Bocchini (J)

Clint Wilson (C)

Achint Chani (A)

Adebiyi Adepoju (A)

Adnan Mahmood (A)

Aisha Mortagy (A)

Ajla Dupljak (A)

Alison Brown (A)

Alpana Waldron (A)

Amanda Cook (A)

Amy Froment (A)

Andrea Hooper (A)

Andrea Margiotta (A)

Andrew Bombardier (A)

Anne Smith (A)

Aswani Bathula (A)

Bari Kowal (B)

Barry Siliverstein (B)

Benjamin Horel (B)

Bret Musser (B)

Brian Bush (B)

Brian Head (B)

Bryan Zhu (B)

Camille Debray (C)

Careta Phillips (C)

Carol Lee (C)

Caryn Trbovic (C)

Catherine Elliott (C)

Chad Fish (C)

Charlie Ni (C)

Charlotte Lyon (C)

Christina Perry (C)

Christine Enciso (C)

Christopher Caira (C)

Christopher Chamak (C)

Christopher Powell (C)

Cliff Baum (C)

Colby Burk (C)

Cynthia Pan (C)

David Liu (D)

David Stein (D)

Daya Gulabani (D)

Deborah Leonard (D)

Denise Bonhomme (D)

Denise Kennedy (D)

Derrick Bramble (D)

Dhanalakshmi Barron (D)

Diana Rofail (D)

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Dona Bianco (D)

Donna Gambaccini (D)

Eduardo Forleo Neto (E)

Edward Jean-Baptiste (E)

Ehsan Bukhari (E)

Elizabeth Bucknam (E)

Emily Nanna (E)

Esther Huffman O'Keefe (E)

Evelyn Gasparino (E)

Georgia Bellingham (G)

Giane Sumner (G)

Grainne Moggan (G)

Grainne Power (G)

Haitao Gao (H)

Haixia Zeng (H)

Heath Gonzalez (H)

Helen Kang (H)

Hibo Noor (H)

Ian Minns (I)

James Donohue (J)

Janice Austin (J)

Janie Parrino (J)

Jeannie Yo (J)

Jenna McDonnell (J)

Jennifer Hamilton (J)

Jessica Boarder (J)

Jing Xiao (J)

Jingchun Yu (J)

Joanne Malia (J)

Joanne Tucciarone (J)

John Strein (J)

Jonathan Cohen (J)

Jordan Ursino (J)

Joseph Im (J)

Joseph Wolken (J)

Karen Browning (K)

Karen Yau (K)

Kenneth Turner (K)

Kimberly Dornheim (K)

Kit Chiu (K)

Kristina McGuire (K)

Kristy Macci (K)

Kurt Ringleben (K)

Kyle Foster (K)

Lacey Douthat (L)

Latora Knighton (L)

Lisa Boersma (L)

Lisa Hersh (L)

Lisa Purcell (L)

Lisa Sherpinsky (L)

Lori Geissler (L)

Marc Dickens (M)

Marco Mancini (M)

Martha Simpkins (M)

Meagan O'Brien (M)

Michael Batchelder (M)

Michael Partridge (M)

Michal Rozanski (M)

Michel Tarabocchia (M)

Michelle Wong (M)

Mivianisse Rodriguez (M)

Moetaz Albizem (M)

Muriel O'Byrne (M)

Nagendher Burra (N)

Neena Sarkar (N)

Nicholas Moore (N)

Nicole Memblatt (N)

Nikki Miocevic (N)

Nirav Shah (N)

Nitin Kumar (N)

Olga Herrera (O)

Patrick Floody (P)

Paul D'Ambrosio (P)

Qin Li (Q)

Rafia Bhore (R)

Rakiyya Ali (R)

Ramya Iyer (R)

Ravikanth Chava (R)

Rinol Alaj (R)

Romana Hosain (R)

Ruchin Gorawala (R)

Ryan Yu (R)

Rylee Fogarty (R)

S Balachandra Dass (SB)

Sagarika Bollini (S)

Samit Ganguly (S)

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Sara Hamon (S)

Sarah Cassimaty (S)

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Wilson Caldwell (W)

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Yasmin Khan (Y)

Commentaires et corrections

Type : CommentIn

Informations de copyright

Références

N Engl J Med. 2021 Feb 25;384(8):693-704

pubmed: 32678530

JAMA. 2020 May 26;323(20):2052-2059

pubmed: 32320003

Ann Intern Med. 2020 Sep 1;173(5):362-367

pubmed: 32491919

Science. 2020 Aug 21;369(6506):1014-1018

pubmed: 32540904

Clin Infect Dis. 2021 Dec 6;73(11):e4400-e4408

pubmed: 32897368

Science. 2020 Nov 27;370(6520):1110-1115

pubmed: 33037066

N Engl J Med. 2019 Dec 12;381(24):2293-2303

pubmed: 31774950

Clin Infect Dis. 2021 Dec 6;73(11):e4197-e4205

pubmed: 32603425

JAMA. 2020 Aug 4;324(5):460-470

pubmed: 32492084

Cell. 2020 May 28;181(5):1036-1045.e9

pubmed: 32416070

Nature. 2020 Aug;584(7821):425-429

pubmed: 32604404

MMWR Morb Mortal Wkly Rep. 2020 Jul 31;69(30):993-998

pubmed: 32730238

J Clin Virol. 2020 Sep;130:104542

pubmed: 32707511

Science. 2020 Aug 21;369(6506):1010-1014

pubmed: 32540901

N Engl J Med. 2020 Jun 11;382(24):2302-2315

pubmed: 32289214

JAMA Intern Med. 2020 Nov 01;180(11):1447-1452

pubmed: 32780793

N Engl J Med. 2020 Feb 20;382(8):727-733

pubmed: 31978945

N Engl J Med. 2021 Jan 21;384(3):229-237

pubmed: 33113295

N Engl J Med. 2020 Apr 30;382(18):1708-1720

pubmed: 32109013

Nature. 2020 May;581(7809):465-469

pubmed: 32235945

N Engl J Med. 2020 Jun 11;382(24):2372-2374

pubmed: 32302078