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

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Date

2021-04-11

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Abstract

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. The primary endpoint was improvement in at least two categories in the 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). The median age was 54 years old, 65.1% were male, and 61% had moderate disease at baseline. The median time from symptom onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups regarding the primary endpoint (risk difference [95% CI]: 5.28% [-3.95; 14.50]; p = 0.15). The rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. The 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% in the INM005 group and 11.4% in the placebo group (risk difference [95% CI]: 0.57 [0.24 to 1.37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. INTERPRETATION: Although not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

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Fil: Lopardo G. Hospital Municipal Dr. Bernardo Houssay. Provincia de Buenos Aires, Argentina. Fundación del Centro de Estudios Infectológicos (FUNCEI); Ciudad Autónoma de Buenos Aires; Argentina
Fil: Belloso WH. Department of Research, Hospital Italiano de Buenos Aires; Ciudad Autónoma de Buenos Aires; Argentina
Fil: Nannini E. Departamento de Enfermedades Infecciosas, Sanatorio Británico; Rosario, Santa Fé; Argentina.
Fil: Colonna M. Inmunova S.A; Villa Lynch, Gral. San Martín; Buenos Aires; Argentina
Fil: Sanguineti S. Inmunova S.A; Villa Lynch, Gral. San Martín; Buenos Aires; Argentina
Fil: Zylberman V. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. Inmunova S.A; Villa Lynch, Gral. San Martín; Buenos Aires; Argentina
Fil: Muñoz L. Inmunova S.A; Villa Lynch, Gral. San Martín; Buenos Aires; Argentina
Fil: Dobarro M. Sanatorio Sagrado Corazón (OSECAC); Ciudad Autónoma de Buenos Aires; Argentina
Fil: Lebersztein G. Sanatorio Sagrado Corazón (OSECAC); Ciudad Autónoma de Buenos Aires; Argentina
Fil: Farina J. Hospital de Alta Complejidad Cuenca Alta S.A.M.I.C. Dr. Néstor Carlos Kirchner; Florencio Varela; Provincia de Buenos Aires; Argentina
Fil: Vidiella G. Sanatorio Agote; Ciudad Autónoma de Buenos Aires; Argentina
Fil: Bertetti A. Sanatorio Güemes; Ciudad Autónoma de Buenos Aires; Argentina
Fil: Crudo F. Hospital Municipal Emilio Zerboni; San Antonio de Areco; Provincia de Buenos Aires; Argentina
Fil: Alzogaray MF. Instituto Medico Platense; La Plata; Provincia de Buenos Aires; Argentina
Fil: Barcelona L. Hospital Municipal Dr. Bernardo Houssay; Florida; Provincia de Buenos Aires; Argentina
Fil: Teijeiro R. Hospital General de Agudos Dr. Ignacio Pirovano; Ciudad Autónoma de Buenos Aires; Argentina
Fil: Lambert S. Hospital de Alta Complejidad Cuenca Alta S.A.M.I.C. Dr. Néstor Carlos Kirchner; Florencio Varela; Provincia de Buenos Aires; Argentina
Fil: Scublinsky D. Clínica Zabala; Ciudad Autónoma de Buenos Aires; Argentina
Fil: Iacono M. Hospital Provincial Neuquén Dr. Castro Rendón; Neuquén; Argentina
Fil: Stanek V. Sección de Infectología, Servicio de Medicina Interna, Hospital Italiano de Buenos Aires; Ciudad Autónoma de Buenos Aires; Argentina
Fil: Solari R. Hospital de Infecciosas Francisco Javier Muñiz; Ciudad Autónoma de Buenos Aires; Argentina
Fil: Cruz P. Centro Gallego de Buenos Aires; Ciudad Autónoma de Buenos Aires; Argentina
Fil: Casas MM. Clínica Adventista Belgrano; Ciudad Autónoma de Buenos Aires; Argentina
Fil: Abusamra L. Hospital Municipal Dr. Diego Thompson; Villa Lynch; Gral. San Martín; Argentina
Fil: Luciardi HL. Hospital Centro de Salud Zenón J. Santillán; San Miguel de Tucumán; Tucumán; Argentina
Fil: Cremona A. Hospital Italiano La Plata; La Plata; Provincia de Buenos Aires; Argentina
Fil: Caruso D. Hospital Español; Ciudad Autónoma de Buenos Aires; Argentina
Fil: de Miguel B. mAbxience; Madrid; España
Fil: Lloret SP. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Argentina
Fil: Millán S. mAbxience; Madrid; España
Fil: Kilstein Y. PHV LATAM, AES; Ciudad Autónoma de Buenos Aires; Argentina
Fil: Pereiro A. Fundación Mundo Sano; Ciudad Autónoma de Buenos Aires; Argentina
Fil: Sued O. Fundación Huésped; Ciudad Autónoma de Buenos Aires; Argentina
Fil: Cahn P. Fundación Huésped; Ciudad Autónoma de Buenos Aires; Argentina
Fil: Spatz L. Inmunova S.A.; Villa Lynch, Gral. San Martín; Buenos Aires; Argentina
Fil: Goldbaum F. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Argentina

Keywords

COVID-19, Inmunoterapia

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URI

https://repositorio.huesped.org.ar/handle/123456789/953

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Articulos científicos