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

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.

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: INM005; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 242
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma de Buenos Aire, Argentina
    • Centro Gallego de Buenos Aires
  • Ciudad Autonoma de Buenos Aire, Argentina
    • Clinica Adventista Belgrano
  • Ciudad Autonoma de Buenos Aire, Argentina
    • Clínica Pasteleros
  • Ciudad Autonoma de Buenos Aire, Argentina
    • Clínica Zabala
  • Ciudad Autonoma de Buenos Aire, Argentina
    • Fundacion 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 Corazon
  • Ciudad Autonoma de Buenos Aires, Argentina, C1180AAD
    • Sanatorio Guemes
  • Ciudad Autonoma de Buenos Aires, Argentina, C1199ABH
    • Hospital Italiano de Buenos Aires
  • Ciudad Autonoma de Buenos Aires, Argentina, C1282AEN
    • Hospital Muñiz
  • Ciudad Autonoma de Buenos Aires, Argentina, C1428
    • Hospital Pirovano
  • Buenos Aires
    • Cañuelas, Buenos Aires, Argentina, B1814
      • Hospital de Cuenca Alta
    • Florencio Varela, Buenos Aires, Argentina
      • Hospital Alta Complejidad "El Cruce" Dr. Néstor Carlos Kirchner
    • Florida, Buenos Aires, Argentina
      • Hospital Prof. Dr. Bernardo A. Houssay
    • La Plata, Buenos Aires, Argentina, B1900AVG
      • Instituto Medico Platense
    • La Plata, Buenos Aires, Argentina
      • Hospital Italiano de La Plata
    • San Antonio de Areco, Buenos Aires, Argentina
      • Hospital Municipal Emilio Zerboni
    • San Martín, Buenos Aires, Argentina
      • Hospital Municipal Dr. Diego E. Thompson
  • Jujuy
    • San Salvador De Jujuy, Jujuy, Argentina
      • Hospital Pablo Soria
  • Neuquen
    • Neuquén, Neuquen, Argentina
      • Hospital Provincial Neuquén "Dr. Eduardo Castro Rendón"
  • Tucuman
    • San Miguel De Tucumán, Tucuman, Argentina
      • Hospital Centro de Salud Zenón J. Santillán

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics evaluation of INM005	INM005 product concentration in serum at different time points after dosing	1 week
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
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
Discharge	Proportion of patients discharged at 28 days	up to 4 weeks
Intensive care unit (ICU) hospitalization	Proportion of patients who require ICU hospitalization	up to 4 weeks
Mechanical ventilation assistance (MVA)	Proportion of patients who require MVA	up to 4 weeks
Mortality	Proportion of patients who die due to complications from COVID19	up to 4 weeks
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti SARS-CoV2 antibodies levels	Measurement of anti SARS-CoV2 antibodies titer levels. IgG (0, 21 days)	3 weeks
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
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
Changes in Ferritin levels	Changes in Ferritin levels will be evaluated at 7 and 21 days as a measurement of disease progression	3 weeks
Changes in LDH levels	Changes in LDH levels will be evaluated at 7 and 21 days as a measurement of disease progression	3 weeks
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
Immunogenicity	Measurement of anti-INM005 antibodies: baseline and 21 days	3 weeks

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2020
• Primary Completion (Actual): November 23, 2020
• Study Completion (Actual): December 30, 2020

Study Registration Dates

• First Submitted: July 29, 2020
• First Submitted That Met QC Criteria: July 30, 2020
• First Posted (Actual): July 31, 2020

Study Record Updates

• Last Update Posted (Actual): February 11, 2021
• Last Update Submitted That Met QC Criteria: February 9, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: CT-INM005-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No