Clinical trial NCT04494984: A Study to Investigate the Pharmacokinetics, Efficacy and Safety of INM005 in Patients With COVID-19.
Official title: A Stage 2/3, Adaptive, Randomized, Controlled, Double-blind Study to Investigate the Pharmacokinetics, Efficacy and Safety of the Hyperimmune Equine Serum (INM005) in Adult Patients With Moderate to Severe Confirmed SARS-CoV2 Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Covid19
Lead sponsor: Inmunova S.A.
Sponsor class: OTHER
First posted: 2020-07-31
Enrollment: 242
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This study will be an adaptive phase 2/3 investigation. First, 12 subjects will be randomly assigned to receive 1 of the 2 treatment regimens (study drug or placebo) in a 1:1 ratio. After the first 6 subjects have been enrolled and have completed 24 hours post treatment of 2nd dose, the IDMC will review the safety data and will inform whether to continue with staggered enrollment. Randomization ratio for subjects in the following stage will be 1:1. The independent data monitoring committee (IDMC) will review safety data after 12, 24, 48 and 96 patients have been enrolled in each arm. The study will then enroll a total of 121 patients in each arm. An interim analysis will be performed after 80% of recruitment has been reached (n=194). The IDMC will analyze the rate of events in the group under "standard of care".
Primary purpose: TREATMENT

Brief summary: This study aims to analyze the efficacy and safety of passive immunotherapy by administering an equine hyperimmune serum (INM005) against the SARS-CoV2 RBD to Covid19 patients. Improvement of the clinical course 28 days after the start of treatment will be evaluated.

Detailed description: The pandemic caused by the new coronavirus has generated a situation unprecedented in recent history, with several million infected and hundreds of thousands of deaths. This disease is easily transmissible by air. Although a high percentage of cases present mild clinical presentation, approximately 15% of patients present moderate to severe cases and 5% require critical care, with respiratory assistance and a high risk of mortality. No effective therapies for the treatment or prevention of SARS.CoV2 have been identified yet. Preliminary evidence indicates that passive immunotherapy with convalescent plasma could alter the clinical course of this infection in a favorable manner. This strategy, even if confirmed as successful, requires voluntary donation by patients who have recovered, not all of whom are eligible as donors, since the antibody response varies in magnitude in different patients. This adaptive stage II/III study aims to analyze the efficacy and safety of passive immunotherapy by administering a purified Fab fraction of equine hyperimmune serum (INM005) generated from antigenic stimulation with the SARS-CoV2 RBD protein, with the objective of neutralizing the interaction of SARS-CoV-2 with its cellular receptor, thus preventing the multiplication of the virus. The safety of this type of equine hyperimmune sera has already been demonstrated in previous and ongoing protocols with a biologically equivalent product against the E. Coli shiga toxin to treat patients with Hemolytic Uremic Syndrome (CT-INM004-01 and CT-INM004-02). In the present study, eligible patients will with moderate to severe symptoms of COVID-19 that require hospitalization will receive two 4 mg/kg doses of INM005, two days apart, with the aim of improving the clinical course of COVID-19 28 days after the start of treatment with the study drug.

Eligibility criteria: Inclusion Criteria:

1. Subjects of both sexes aged 18 to 79 years of age
2. SARS-CoV-2 infection confirmed by PCR for virus detection
3. Patients with moderate or severe disease by NIH definition, which requires hospitalization.
4. Acceptance to participate in the study by the signature of the informed consent by a subject or their relative, if applicable
5. Be within 10 days of the onset of symptoms at the time of the Screening visit according to a case definition from the National Ministry of Health
6. Female patients of child-bearing age with negative pregnancy test

Exclusion Criteria:

1. Patients who have received treatment with plasma from COVID-19 convalescents.
2. Patients who are participating in other therapeutic clinical trials
3. Patients who require mechanical respiratory assistance or are hospitalized in the ICU at the time of the screening visit.
4. History of anaphylaxis, prior administration of equine serum (por example, anti-tetanus serum or anti-ophidic serum or anti-arachnid toxin serum) or allergic reaction due to contact or exposure to horses.
5. Pregnant or breastfeeding women
6. Patients who, at the doctor's discretion, are likely to die within the next 30 days due to a concomitant disease other than the study disease
7. Patients who are expected to be referred to another institution within 72 hours of enrollment, which prevents proper follow-up of that patient.

Primary outcomes:
measure: Clinical changes in COVID-19 symptoms
timeFrame: 4 weeks
Secondary outcomes:
measure: Pharmacokinetics evaluation of INM005
timeFrame: 1 week
measure: Time to progression of disease
timeFrame: 4 weeks
measure: Disease progression
timeFrame: up to 2 weeks
measure: Discharge
timeFrame: up to 4 weeks
measure: Intensive care unit (ICU) hospitalization
timeFrame: up to 4 weeks
measure: Mechanical ventilation assistance (MVA)
timeFrame: up to 4 weeks
measure: Mortality
timeFrame: up to 4 weeks
measure: Changes in viral load
timeFrame: up to 3 weeks
Other outcomes:
measure: Anti SARS-CoV2 antibodies levels
timeFrame: 3 weeks
measure: Changes in Troponin T levels
timeFrame: 3 weeks
measure: Changes in D-dimer levels
timeFrame: 3 weeks
measure: Changes in Ferritin levels
timeFrame: 3 weeks
measure: Changes in LDH levels
timeFrame: 3 weeks
measure: Changes in C-reactive protein levels
timeFrame: 3 weeks
measure: Immunogenicity
timeFrame: 3 weeks
Locations:
city: Cañuelas
country: Argentina
facility: Hospital de Cuenca Alta
state: Buenos Aires
city: Florencio Varela
country: Argentina
facility: Hospital Alta Complejidad "El Cruce" Dr. Néstor Carlos Kirchner
state: Buenos Aires
city: Florida
country: Argentina
facility: Hospital Prof. Dr. Bernardo A. Houssay
state: Buenos Aires
city: La Plata
country: Argentina
facility: Instituto Medico Platense
state: Buenos Aires
city: La Plata
country: Argentina
facility: Hospital Italiano de La Plata
state: Buenos Aires
city: San Antonio de Areco
country: Argentina
facility: Hospital Municipal Emilio Zerboni
state: Buenos Aires
city: San Martín
country: Argentina
facility: Hospital Municipal Dr. Diego E. Thompson
state: Buenos Aires
city: San Salvador De Jujuy
country: Argentina
facility: Hospital Pablo Soria
state: Jujuy
city: Neuquén
country: Argentina
facility: Hospital Provincial Neuquén "Dr. Eduardo Castro Rendón"
state: Neuquen
city: San Miguel De Tucumán
country: Argentina
facility: Hospital Centro de Salud Zenón J. Santillán
state: Tucuman
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Sanatorio Guemes
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Muñiz
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Pirovano
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Centro Gallego de Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Clínica Adventista Belgrano
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Clínica Pasteleros
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Clínica Zabala
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Fundación Favaloro
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Hospital Español de Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Hospital G. A. Carlos G. Durand
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Sanatorio Agote
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Sanatorio Sagrado Corazón
Study officials:
affiliation: Inmunova S.A.
name: Santiago Sanguineti, Ph.D.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Piechotta V, Iannizzi C, Chai KL, Valk SJ, Kimber C, Dorando E, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Estcourt LJ, Skoetz N. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 May 20;5(5):CD013600. doi: 10.1002/14651858.CD013600.pub4.
citation: Lopardo G, Belloso WH, Nannini E, Colonna M, Sanguineti S, Zylberman V, Munoz L, Dobarro M, Lebersztein G, Farina J, Vidiella G, Bertetti A, Crudo F, Alzogaray MF, Barcelona L, Teijeiro R, Lambert S, Scublinsky D, Iacono M, Stanek V, Solari R, Cruz P, Casas MM, Abusamra L, Luciardi HL, Cremona A, Caruso D, de Miguel B, Lloret SP, Millan S, Kilstein Y, Pereiro A, Sued O, Cahn P, Spatz L, Goldbaum F; INM005 Study Group. 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. EClinicalMedicine. 2021 Apr;34:100843. doi: 10.1016/j.eclinm.2021.100843. Epub 2021 Apr 11.