Safety and Effectiveness of an Immunobiological Drug in CoViD-19

NCT ID: NCT04913779

Last Updated: 2021-09-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-01
• Study Completion Date: 2021-12-31

Brief Summary

The aims of this study is to analyze the efficacy and safety of a passive immunotherapy strategy using hyperimmune equine serum known as Anti-SARS-CoV-2 elaborated by the National Institute for the Production of Biologicals (ANLIS-Malbrán) as an addition to the standard therapeutic approach for hospitalized patients with COVID-19, in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection aged 18 to 80 years.

Detailed Description

This is an adaptive phase II/III study that aims to analyze the efficacy and safety of a immunobiological drug (Anti SARS-CoV-2) in the treatment of CoViD-19. This treatment is a passive immunotherapy strategy developed as a purified F(ab')2 fraction of equine hyperimmune serum (Anti-SARS-CoV-2). The equine serum was generated from antigenic stimulation with the SARS-CoV-2 receptor binding domain (RBD) purified protein.

This type of product (equine hyperimmune serum F(ab')2) has been widely used in our country in the last 100 years with satisfactory results and an acceptable safety profile in the treatment of accidents with poisonous animals such as anti-loxosceles, anti -latrodectus, anti-scorpionic, and anti-phoneutria, anti-bothropic, anti-micrurus, and anti-crotalic sera, all developed by the National Institute of Biological Production (ANLIS-Malbrán) and distributed free of charge in public hospitals in the country .

In the present study, evaluates the effect and safety of this immunobiological treatment in patients with COVID-19 that require hospitalization.

Conditions

COVID-19 Pneumonia; COVID-19 Respiratory Infection; Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Anti-SARS-CoV-2

Administration of 10 ml of a concentrated equine hyperimmune serum solution with neutralizing activity of SARS-CoV-2 not less than1/5120, administered in slow intravenous infusion (10 ml diluted in100 ml of physiological solution, administered over 50 to 60 minutes in slow drip), produced by ANLIS-Malbrán, administered twice (time 0 when incorporated into the study -initial dose- and at 48 hours -second dose-).

Group Type: ACTIVE_COMPARATOR

Anti-SARS-CoV-2

Intervention Type: DRUG

Purified F(ab')2 Fragments of Equine hyperimmune Serum with anti-SARS-CoV-2 neutralizing activity (titer 1/5120 or higher)

Placebo

Administration of 10 ml of a control-solution with no-neutralizing activity of SARS-CoV-2, administered in slow intravenous infusion (10ml diluted in 100 ml of physiological solution, administered over 50 to60 minutes in slow drip), produced by ANLIS-Malbrán, administered twice (time 0when incorporated into the study -initial dose- and at 48 hours -second dose-).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Administration of 10 ml of a control-solution without neutralizing activity against SARS-CoV-2, administered in slow intravenous infusion (10 ml diluted in 100 ml of saline solution, administered over 50 to 60 minutes in slow drip), produced by ANLIS-Malbrán, administered twice (time 0 when incorporated into the study -initial dose- and at 48 hours -second dose-).

Interventions

Anti-SARS-CoV-2

Purified F(ab')2 Fragments of Equine hyperimmune Serum with anti-SARS-CoV-2 neutralizing activity (titer 1/5120 or higher)

Intervention Type: DRUG

Placebo

Administration of 10 ml of a control-solution without neutralizing activity against SARS-CoV-2, administered in slow intravenous infusion (10 ml diluted in 100 ml of saline solution, administered over 50 to 60 minutes in slow drip), produced by ANLIS-Malbrán, administered twice (time 0 when incorporated into the study -initial dose- and at 48 hours -second dose-).

Intervention Type: DRUG

Other Intervention Names

Purified F(ab')2 Fragments of Equine hyperimmune Serum; F(ab')2 Fragments; Passive Immunotherapy; Equine F(ab')2 Fragments; Hyperimmune Equine Serum; Treatment Group; Control Group

Eligibility Criteria

Inclusion Criteria

1. Subjects over 18 years old and under 80 years old.

2. Positive results by RT-PCR for SARS CoV-2

3. Clinical picture compatible with respiratory compromise in the form of pneumonia attributed to COVID-19 (Stage 3, 4 or 5 according to the WHO scale), lasting up to 72 hours from the onset of symptoms to their evaluation to be incorporated into the study.

4. Patient with good disposition towards the study and that signs the informed consent.

Exclusion Criteria

1. Patients with clinical disease corresponding to mild / asymptomatic forms (Absence of radiological infiltrate and risk factors, with normal auscultation and arterial saturation of oxygen (SatO2) greater than 95%)

2. Patients with clinical disease corresponding to severe forms (Severe pneumonia: presence of severity criteria (ATS / IDSA), one of two major or three minor criteria.)

3. Patients who have received other therapeutic strategies in the framework of an experimental study that make it difficult to evaluate the results obtained, including (but not limited to): convalescent plasma, lopinavir / ritonavir, hydroxychloroquine, and azithromycin.

4. Pregnant or lactating women.

5. Women of childbearing potential not using an effective contraceptive method (withdrawal, intrauterine device, or oral contraceptives).

6. History of severe anaphylactic reaction with the administration of equine plasma.

7. Patients with comorbidities that justify a risk of high mortality from causes independent of SARS-CoV-2 infection (eg, stage IV cancer)

8. Patient who does not consent to participate.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Administracion Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran

OTHER_GOV

Sponsor Role: lead

Responsible Party

Guillermo Alberto Keller

Physician. Specialist in internal medicine and clinical pharmacology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Guillermo A Keller, PhD

Role: PRINCIPAL_INVESTIGATOR

INPB - ANLIS Malbrán

Locations

Hospital General de Agudos Donación Francisco J. Santojanni

Buenos Aires, , Argentina

Site Status: RECRUITING

Countries

Argentina

Central Contacts

Guillermo A Keller, MD PhD

Role: CONTACT

gkeller@anlis.gob.ar

011-4961-0943

Claudio Bonel, PhD

Role: CONTACT

cbonel@anlis.gob.ar

011-4303-1801

Facility Contacts

Guillermo A Keller, MD PhD

Role: primary

gkeller@anlis.gob.ar

01149610943

Claudio Bonel, PhD

Role: backup

cbonel@anlis.gob.ar

011-4303-2492

Other Identifiers

PRIISA.BA 2578

Identifier Type: REGISTRY

Identifier Source: secondary_id

RENIS IS003268

Identifier Type: REGISTRY

Identifier Source: secondary_id

DI-2021-2196-APN-ANMAT#MS

Identifier Type: OTHER

Identifier Source: secondary_id

INPB001

Identifier Type: -

Identifier Source: org_study_id