RBD-specific polyclonal F(ab´) 2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial.

Autor:	Lopardo G; Hospital Municipal Dr. Bernardo Houssay, Pte Hipólito Yrigoyen 1757, Florida, Provincia de Buenos Aires, Argentina.; Fundación del Centro de Estudios Infectológicos (FUNCEI), French 3085, Ciudad Autónoma de Buenos Aires, Buenos Aires C1425, Argentina., Belloso WH; Department of Research, Hospital Italiano de Buenos Aires. Pres. Tte. Gral. Juan Domingo Perón 4190, Ciudad Autónoma de Buenos Aires, Buenos Aires C1199, Argentina., Nannini E; Departamento de Enfermedades Infecciosas, Sanatorio Británico, Paraguay 40, Rosario, Santa Fé S2000 CVB, Argentina.; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina., Colonna M; Inmunova S.A., 25 de mayo 1021, Villa Lynch, Gral. San Martín, Buenos Aires CP B1650HMP, Argentina., Sanguineti S; Inmunova S.A., 25 de mayo 1021, Villa Lynch, Gral. San Martín, Buenos Aires CP B1650HMP, Argentina., Zylberman V; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.; Inmunova S.A., 25 de mayo 1021, Villa Lynch, Gral. San Martín, Buenos Aires CP B1650HMP, Argentina., Muñoz L; Inmunova S.A., 25 de mayo 1021, Villa Lynch, Gral. San Martín, Buenos Aires CP B1650HMP, Argentina., Dobarro M; Sanatorio Sagrado Corazón (OSECAC), Bartolomé Mitre 1955, Ciudad Autónoma de Buenos Aires, Buenos Aires CP1039, Argentina., Lebersztein G; Sanatorio Sagrado Corazón (OSECAC), Bartolomé Mitre 1955, Ciudad Autónoma de Buenos Aires, Buenos Aires CP1039, Argentina., Farina J; Hospital de Alta Complejidad Cuenca Alta S.A.M.I.C. Dr. Néstor Carlos Kirchner, RP6, Cañuelas, Provincia de Buenos Aires, Argentina., Vidiella G; Sanatorio Agote. Dr. Luis Agote 2477, Ciudad Autónoma de Buenos Aires, Buenos Aires C1425 EOE, Argentina., Bertetti A; Sanatorio Güemes, Francisco Acuña de Figueroa 1240, Ciudad Autónoma de Buenos Aires, Buenos Aires C1180, Argentina., Crudo F; Hospital Municipal Emilio Zerboni, Moreno 90, San Antonio de Areco, Provincia de Buenos Aires B2760, Argentina.; Universidad Nacional de San Antonio de Areco, Av. Güiraldes 689, San Antonio de Areco, Provincia de Buenos Aires, Argentina., Alzogaray MF; Instituto Medico Platense. Av. 51 315, La Plata, Provincia de Buenos Aires B1900 AVG, Argentina., Barcelona L; Hospital Municipal Dr. Bernardo Houssay, Pte Hipólito Yrigoyen 1757, Florida, Provincia de Buenos Aires, Argentina., Teijeiro R; Hospital General de Agudos Dr. Ignacio Pirovano, Av. Monroe 3555, Ciudad Autónoma de Buenos Aires, Buenos Aires C1428, Argentina., Lambert S; Hospital de Alta Complejidad El Cruce Néstor Kirchner, Av. Calchaquí 5401, Florencio Varela, Provincia de Buenos Aires, Argentina., Scublinsky D; Clínica Zabala. Av. Cabildo 1295, Ciudad Autónoma de Buenos Aires, Buenos Aires C1426 AAM, Argentina., Iacono M; Hospital Provincial Neuquén Dr. Castro Rendón, Buenos Aires 450, Neuquén Q8300, Argentina., Stanek V; Sección de Infectología, Servicio de Medicina Interna, Hospital Italiano de Buenos Aires. Pres. Tte. Gral. Juan Domingo Perón 4190, Ciudad Autónoma de Buenos Aires, Buenos Aires C1199, Argentina., Solari R; Hospital de Infecciosas Francisco Javier Muñiz, Uspallata 2272, Ciudad Autónoma de Buenos Aires, Buenos Aires C1282, Argentina., Cruz P; Centro Gallego de Buenos Aires, Av. Belgrano 2199, Ciudad Autónoma de Buenos Aires, Buenos Aires C1096, Argentina., Casas MM; Clínica Adventista Belgrano. Estomba 1710, Ciudad Autónoma de Buenos Aires, Buenos Aires C1430 EGF, Argentina., Abusamra L; Hospital Municipal Dr. Diego Thompson, Avellaneda 33, Villa Lynch, Gral. San Martín, Buenos Aires B1650, Argentina., Luciardi HL; Hospital Centro de Salud Zenón J. Santillán, Av. Avellaneda 750, San Miguel de Tucumán, Tucumán T4000, Argentina., Cremona A; Hospital Italiano La Plata, Av. 51, La Plata, Provincia de Buenos Aires B1900, Argentina., Caruso D; Hospital Español, Av. Belgrano 2975, Ciudad Autónoma de Buenos Aires, Buenos Aires C1209, Argentina., de Miguel B; mAbxience, Manuel Pombo Angulo 28, 3rd floor, Madrid 28050, Spain., Lloret SP; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.; Departamento de Docencia e Investigación, Facultad de Ciencias Médicas, Universidad Católica Argentina, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.; Universidad Abierta Interamericana, Centro de Altos Estudios en Ciencias Humanas y de la Salud (UAI-CAECIHS), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. San Juan 951, Ciudad Autónoma de Buenos Aires, Buenos Aires C1147 AAH, Argentina., Millán S; mAbxience, Manuel Pombo Angulo 28, 3rd floor, Madrid 28050, Spain., Kilstein Y; PHV LATAM, AES, Amenábar 3851, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina., Pereiro A; Fundación Mundo Sano, Paraguay 1535, Ciudad Autónoma de Buenos Aires, Buenos Aires C1061ABC, Argentina., Sued O; Fundación Huésped, Pasaje Ángel Peluffo 3932PB, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina., Cahn P; Fundación Huésped, Pasaje Ángel Peluffo 3932PB, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina., Spatz L; Inmunova S.A., 25 de mayo 1021, Villa Lynch, Gral. San Martín, Buenos Aires CP B1650HMP, Argentina., Goldbaum F; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.; Inmunova S.A., 25 de mayo 1021, Villa Lynch, Gral. San Martín, Buenos Aires CP B1650HMP, Argentina.; Fundación Instituto Leloir, IIBBA-CONICET. Av. Patricias Argentinas 435, Buenos Aires C1405BWE, Argentina.; CRIP - Centro de Rediseño e Ingeniería de Proteínas UNSAM Campus Miguelete. 25 de Mayo y Francia Villa Lynch, Gral. San Martín, Buenos Aires B1650HMK, Argentina.
Jazyk:	angličtina
Zdroj:	EClinicalMedicine [EClinicalMedicine] 2021 Apr; Vol. 34, pp. 100843. Date of Electronic Publication: 2021 Apr 11.
DOI:	10.1016/j.eclinm.2021.100843
Abstrakt:	Background: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. Methods: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). Findings: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 ( n  = 118) or placebo ( n  = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; p  = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. Interpretation: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease. Competing Interests: MC, SS, VZ, LM, LS, FG received grants from Ministries of Science and Production of Argentina. MD, JF, GV, AB, FC, MFA, LB, RT, SL, DS, MI, VS, RS, PC, MMC, LA, HLL, AC, DC declare reimbursement for conduction of clinical trial as investigator of the study. PC, OS, YK report other funds from Inmunova S.A. EN, GL, WHB, SPLL report personal fees from Inmunova S.A. SM reports non-financial support from Inmunova S.A. AP, B de M, Gabriel L declare no competing interests. SPLL declare personal fees from Movement Disorders Society, Laboratorio Elea and Merck pharmaceuticals. MC, SS, VZ, LM, LS are employed by Inmunova S.A. (© 2021 The Author(s).)
Databáze:	MEDLINE
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