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

Sponsor

Inmunova S.A. (Other)

Overall Status

Completed

CT.gov ID

NCT04494984

Collaborator

(none)

242

Enrollment

Locations

Arms

5.1

Actual Duration (Months)

10.5

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Covid19	Drug: INM005 Drug: Placebo	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

242 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

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".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".

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

A Double-blind, Placebo-controlled, sealed-envelope based. Access to unblinded interim results will be limited to the DMC and unblinded statistician

Primary Purpose:

Treatment

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.

Actual Study Start Date :

Jul 27, 2020

Actual Primary Completion Date :

Nov 23, 2020

Actual Study Completion Date :

Dec 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active 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).	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 Comparator: 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).	Drug: 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.

Arm

Intervention/Treatment

Active Comparator: Active

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).

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 Comparator: 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).

Drug: 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.

Outcome Measures

Primary Outcome Measures

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

Pharmacokinetics evaluation of INM005 [1 week]
INM005 product concentration in serum at different time points after dosing
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).
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.
Discharge [up to 4 weeks]
Proportion of patients discharged at 28 days
Intensive care unit (ICU) hospitalization [up to 4 weeks]
Proportion of patients who require ICU hospitalization
Mechanical ventilation assistance (MVA) [up to 4 weeks]
Proportion of patients who require MVA
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.

Other Outcome Measures

Anti SARS-CoV2 antibodies levels [3 weeks]
Measurement of anti SARS-CoV2 antibodies titer levels. IgG (0, 21 days)
Changes in Troponin T levels [3 weeks]
Changes in Troponin T levels will be evaluated at 7 and 21 days as a measurement of disease progression
Changes in D-dimer levels [3 weeks]
Changes in D-dimer levels will be evaluated at 7 and 21 days as a measurement of disease progression
Changes in Ferritin levels [3 weeks]
Changes in Ferritin levels will be evaluated at 7 and 21 days as a measurement of disease progression
Changes in LDH levels [3 weeks]
Changes in LDH levels will be evaluated at 7 and 21 days as a measurement of disease progression
Changes in C-reactive protein levels [3 weeks]
Changes in C-reactive protein levels will be evaluated at 7 and 21 days as a measurement of disease progression
Immunogenicity [3 weeks]
Measurement of anti-INM005 antibodies: baseline and 21 days

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 79 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects of both sexes aged 18 to 79 years of age
SARS-CoV-2 infection confirmed by PCR for virus detection
Patients with moderate or severe disease by NIH definition, which requires hospitalization.
Acceptance to participate in the study by the signature of the informed consent by a subject or their relative, if applicable
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
Female patients of child-bearing age with negative pregnancy test

Exclusion Criteria:

Patients who have received treatment with plasma from COVID-19 convalescents.
Patients who are participating in other therapeutic clinical trials
Patients who require mechanical respiratory assistance or are hospitalized in the ICU at the time of the screening visit.
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.
Pregnant or breastfeeding women
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
Patients who are expected to be referred to another institution within 72 hours of enrollment, which prevents proper follow-up of that patient.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital de Cuenca Alta	Cañuelas	Buenos Aires	Argentina	B1814
2	Hospital Alta Complejidad "El Cruce" Dr. Néstor Carlos Kirchner	Florencio Varela	Buenos Aires	Argentina
3	Hospital Prof. Dr. Bernardo A. Houssay	Florida	Buenos Aires	Argentina
4	Instituto Medico Platense	La Plata	Buenos Aires	Argentina	B1900AVG
5	Hospital Italiano de La Plata	La Plata	Buenos Aires	Argentina
6	Hospital Municipal Emilio Zerboni	San Antonio de Areco	Buenos Aires	Argentina
7	Hospital Municipal Dr. Diego E. Thompson	San Martín	Buenos Aires	Argentina
8	Hospital Pablo Soria	San Salvador De Jujuy	Jujuy	Argentina
9	Hospital Provincial Neuquén "Dr. Eduardo Castro Rendón"	Neuquén	Neuquen	Argentina
10	Hospital Centro de Salud Zenón J. Santillán	San Miguel De Tucumán	Tucuman	Argentina
11	Sanatorio Guemes	Ciudad Autonoma de Buenos Aires		Argentina	C1180AAD
12	Hospital Italiano de Buenos Aires	Ciudad Autonoma de Buenos Aires		Argentina	C1199ABH
13	Hospital Muñiz	Ciudad Autonoma de Buenos Aires		Argentina	C1282AEN
14	Hospital Pirovano	Ciudad Autonoma de Buenos Aires		Argentina	C1428
15	Centro Gallego de Buenos Aires	Ciudad Autonoma de Buenos Aire		Argentina
16	Clínica Adventista Belgrano	Ciudad Autonoma de Buenos Aire		Argentina
17	Clínica Pasteleros	Ciudad Autonoma de Buenos Aire		Argentina
18	Clínica Zabala	Ciudad Autonoma de Buenos Aire		Argentina
19	Fundación Favaloro	Ciudad Autonoma de Buenos Aire		Argentina
20	Hospital Español de Buenos Aires	Ciudad Autonoma de Buenos Aire		Argentina
21	Hospital G. A. Carlos G. Durand	Ciudad Autonoma de Buenos Aire		Argentina
22	Sanatorio Agote	Ciudad Autonoma de Buenos Aire		Argentina
23	Sanatorio Sagrado Corazón	Ciudad Autonoma de Buenos Aire		Argentina

Sponsors and Collaborators

Inmunova S.A.

Investigators

Study Director: Santiago Sanguineti, Ph.D., Inmunova S.A.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Inmunova S.A.

ClinicalTrials.gov Identifier:

NCT04494984

Other Study ID Numbers:

CT-INM005-01

First Posted:

Jul 31, 2020

Last Update Posted:

Feb 11, 2021

Last Verified:

Feb 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

COVID-19

Study Results

No Results Posted as of Feb 11, 2021