A Study to Investigate the Pharmacokinetics, Efficacy and Safety of INM005 in Patients With COVID-19.

Phase 2

Completed

• Conditions: Covid19
• Interventions: Drug: Placebo; Drug: INM005

• Registration Number: NCT04494984
• Lead Sponsor: Inmunova S.A.

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.

Study Timeline

• Study Start: 2020-07-27
• Study First Submitted: 2020-07-29
• Study First Submitted QC: 2020-07-30
• Study First Posted: 2020-07-31
• Primary Completion: 2020-11-23
• Study Completion: 2020-12-30
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-09
• Last Update Posted: 2021-02-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 242

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Subjects will receive a 1st intravenous dose of Placebo and a 2nd intravenous dose of Placebo. Each dose will be separated by 48 h (± 2 h).
Active	INM005	Subjects will receive a 1st intravenous dose of 4 mg/kg INM005 (Anti-SARS-CoV-2 hyperimmune equine immunoglobulin F\[ab'\]2 fragments) and a 2nd intravenous dose of 4 mg/kg of INM005. Each dose will be separated by 48 h (± 2 h).

Primary Outcome Measures

Name	Time	Method
Clinical changes in COVID-19 symptoms	4 weeks	The primary endpoint will be the proportion of patients who show a change in symptoms 28 days after the administration of the first dose. A responding subject is defined as a subject with improvement in at least 2 categories on the 8-point World Health Organization (WHO) ordinal scale of clinical status or a subject who is discharged.

Secondary Outcome Measures

Name	Time	Method
Disease progression	up to 2 weeks	Proportion of patients who present change in at least 2 categories on the 8-point WHO ordinal scale of clinical status at 7 and 14 days after the start of the treatment.
Mechanical ventilation assistance (MVA)	up to 4 weeks	Proportion of patients who require MVA
Time to progression of disease	4 weeks	Time to achieve a change in at least 2 categories on the 8-point WHO ordinal scale of clinical status.; Time to discharge (days). Time to intensive care unit (ICU) discharge (days).
Discharge	up to 4 weeks	Proportion of patients discharged at 28 days
Pharmacokinetics evaluation of INM005	1 week	INM005 product concentration in serum at different time points after dosing
Intensive care unit (ICU) hospitalization	up to 4 weeks	Proportion of patients who require ICU hospitalization
Mortality	up to 4 weeks	Proportion of patients who die due to complications from COVID19
Changes in viral load	up to 3 weeks	Change in viral load from baseline to 7 and 21 days after the start of the treatment.

Trial Locations

Locations (23)

Hospital de Cuenca Alta; 🇦🇷 Cañuelas, Buenos Aires, Argentina

Clínica Pasteleros; 🇦🇷 Ciudad Autonoma de Buenos Aire, Argentina

Hospital G. A. Carlos G. Durand; 🇦🇷 Ciudad Autonoma de Buenos Aire, Argentina

Sanatorio Sagrado Corazón; 🇦🇷 Ciudad Autonoma de Buenos Aire, Argentina

Hospital Alta Complejidad "El Cruce" Dr. Néstor Carlos Kirchner; 🇦🇷 Florencio Varela, Buenos Aires, Argentina

Hospital Prof. Dr. Bernardo A. Houssay; 🇦🇷 Florida, Buenos Aires, Argentina

Hospital Municipal Emilio Zerboni; 🇦🇷 San Antonio de Areco, Buenos Aires, Argentina

Instituto Medico Platense; 🇦🇷 La Plata, Buenos Aires, Argentina

Hospital Municipal Dr. Diego E. Thompson; 🇦🇷 San Martín, Buenos Aires, Argentina

Hospital Pablo Soria; 🇦🇷 San Salvador De Jujuy, Jujuy, Argentina

Hospital Provincial Neuquén "Dr. Eduardo Castro Rendón"; 🇦🇷 Neuquén, Neuquen, Argentina

Clínica Zabala; 🇦🇷 Ciudad Autonoma de Buenos Aire, Argentina

Hospital Italiano de La Plata; 🇦🇷 La Plata, Buenos Aires, Argentina

Sanatorio Guemes; 🇦🇷 Ciudad Autonoma de Buenos Aires, Argentina

Hospital Centro de Salud Zenón J. Santillán; 🇦🇷 San Miguel De Tucumán, Tucuman, Argentina

Hospital Italiano de Buenos Aires; 🇦🇷 Ciudad Autonoma de Buenos Aires, Argentina

Centro Gallego de Buenos Aires; 🇦🇷 Ciudad Autonoma de Buenos Aire, Argentina

Clínica Adventista Belgrano; 🇦🇷 Ciudad Autonoma de Buenos Aire, Argentina

Hospital Muñiz; 🇦🇷 Ciudad Autonoma de Buenos Aires, Argentina

Hospital Pirovano; 🇦🇷 Ciudad Autonoma de Buenos Aires, Argentina

Fundación Favaloro; 🇦🇷 Ciudad Autonoma de Buenos Aire, Argentina

Sanatorio Agote; 🇦🇷 Ciudad Autonoma de Buenos Aire, Argentina

Hospital Español de Buenos Aires; 🇦🇷 Ciudad Autonoma de Buenos Aire, Argentina