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

Covid19 Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04494984
• Other study ID #: CT-INM005-01
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 27, 2020
• Est. completion date: December 30, 2020

Study information

• Verified date: February 2021
• Source: Inmunova S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 242
• Est. completion date: December 30, 2020
• Est. primary completion date: November 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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.

Related Conditions & MeSH terms

• Covid19

Intervention

Drug:
• INM005
The IMP dose to be studied will be 4 mg of protein/kg of subject's weight. The IMP will be added to the 100 mL infusion bag of saline solution. Doses will be administered as an infusion at 2.0 mL/min over 50 min with an interval of 48 h between doses.
• Placebo
Placebo substance will be added to the 100 mL infusion bag of saline solution. Doses will be administered as an infusion at 2.0 mL/min over 50 min with an interval of 48 h between doses.

Locations

Country	Name	City	State
Argentina	Hospital de Cuenca Alta	Cañuelas	Buenos Aires
Argentina	Centro Gallego de Buenos Aires	Ciudad Autonoma de Buenos Aire
Argentina	Clínica Adventista Belgrano	Ciudad Autonoma de Buenos Aire
Argentina	Clínica Pasteleros	Ciudad Autonoma de Buenos Aire
Argentina	Clínica Zabala	Ciudad Autonoma de Buenos Aire
Argentina	Fundación Favaloro	Ciudad Autonoma de Buenos Aire
Argentina	Hospital Español de Buenos Aires	Ciudad Autonoma de Buenos Aire
Argentina	Hospital G. A. Carlos G. Durand	Ciudad Autonoma de Buenos Aire
Argentina	Sanatorio Agote	Ciudad Autonoma de Buenos Aire
Argentina	Sanatorio Sagrado Corazón	Ciudad Autonoma de Buenos Aire
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autonoma de Buenos Aires
Argentina	Hospital Muñiz	Ciudad Autonoma de Buenos Aires
Argentina	Hospital Pirovano	Ciudad Autonoma de Buenos Aires
Argentina	Sanatorio Guemes	Ciudad Autonoma de Buenos Aires
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 Italiano de La Plata	La Plata	Buenos Aires
Argentina	Instituto Medico Platense	La Plata	Buenos Aires
Argentina	Hospital Provincial Neuquén "Dr. Eduardo Castro Rendón"	Neuquén	Neuquen
Argentina	Hospital Municipal Emilio Zerboni	San Antonio de Areco	Buenos Aires
Argentina	Hospital Municipal Dr. Diego E. Thompson	San Martín	Buenos Aires
Argentina	Hospital Centro de Salud Zenón J. Santillán	San Miguel De Tucumán	Tucuman
Argentina	Hospital Pablo Soria	San Salvador De Jujuy	Jujuy

Sponsors (1)

Lead Sponsor	Collaborator
Inmunova S.A.

Country where clinical trial is conducted

Argentina, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Anti SARS-CoV2 antibodies levels	Measurement of anti SARS-CoV2 antibodies titer levels. IgG (0, 21 days)	3 weeks
Other	Changes in Troponin T levels	Changes in Troponin T levels will be evaluated at 7 and 21 days as a measurement of disease progression	3 weeks
Other	Changes in D-dimer levels	Changes in D-dimer levels will be evaluated at 7 and 21 days as a measurement of disease progression	3 weeks
Other	Changes in Ferritin levels	Changes in Ferritin levels will be evaluated at 7 and 21 days as a measurement of disease progression	3 weeks
Other	Changes in LDH levels	Changes in LDH levels will be evaluated at 7 and 21 days as a measurement of disease progression	3 weeks
Other	Changes in C-reactive protein levels	Changes in C-reactive protein levels will be evaluated at 7 and 21 days as a measurement of disease progression	3 weeks
Other	Immunogenicity	Measurement of anti-INM005 antibodies: baseline and 21 days	3 weeks
Primary	Clinical changes in COVID-19 symptoms	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.	4 weeks
Secondary	Pharmacokinetics evaluation of INM005	INM005 product concentration in serum at different time points after dosing	1 week
Secondary	Time to progression of disease	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).	4 weeks
Secondary	Disease progression	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.	up to 2 weeks
Secondary	Discharge	Proportion of patients discharged at 28 days	up to 4 weeks
Secondary	Intensive care unit (ICU) hospitalization	Proportion of patients who require ICU hospitalization	up to 4 weeks
Secondary	Mechanical ventilation assistance (MVA)	Proportion of patients who require MVA	up to 4 weeks
Secondary	Mortality	Proportion of patients who die due to complications from COVID19	up to 4 weeks
Secondary	Changes in viral load	Change in viral load from baseline to 7 and 21 days after the start of the treatment.	up to 3 weeks