Safety and Effectiveness of an Immunobiological Drug in CoViD-19

NCT04913779 | Unknown Phase 2 DMC

• 4 other identifiers: INPB001PRIISA.BA 2578RENIS IS003268DI-2021-2196-APN-ANMAT#MS
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Anti-SARS-CoV-2; Purified F(ab')2 Fragments; Passive immunotherapy; Equine Serum

Outcome Measures

Primary Outcomes (1)

• Change in time needed to clinical improvement

  In subjects admitted to the general ward for active infection by SARS-CoV-2 and a clinical picture of pneumonia who receive supportive treatment recommended by the guidelines of the Ministry of Health of the Argentine Nation (Population), if slow intravenous administration of Anti SARS-CoV-2 in two doses 48 hours apart (Intervention) added to supportive treatment, compared to supportive treatment alone (patients will receive slow intravenous administration of a placebo solution in two doses 48 hours apart to maintain the "blind" as Comparator), changes the time needed to clinical improvement (Outcome), during 28 days after the assignment (Time).

  Reached each day between day 1 and 28 post-inclusion in the study

Secondary Outcomes (14)

• Change in the number of patients in each World Health Organization (WHO) Ordinal Scale Category (0 to 8 being 0 better and 8 worse)

  days 7, 14 and 21 post-inclusion

• Change in Mortality rate

  28 days post-inclusion

• Change in Mechanical Ventilation Requirement rate

  28 days post-inclusion

• Change in duration of oxygen treatment requirement

  28 days post-inclusion

• Change in Length of Hospitalization

  28 days post-inclusion

Study Arms (2)

Anti-SARS-CoV-2

ACTIVE COMPARATOR

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-).

Drug: Anti-SARS-CoV-2

Placebo

PLACEBO COMPARATOR

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-).

Drug: Placebo

Interventions

Anti-SARS-CoV-2 DRUG

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

Also known as: 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

Anti-SARS-CoV-2

Placebo 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-).

Also known as: Control Group

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects over 18 years old and under 80 years old.
• Positive results by RT-PCR for SARS CoV-2
• 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.
• Patient with good disposition towards the study and that signs the informed consent.

You may not qualify if:

• 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%)
• Patients with clinical disease corresponding to severe forms (Severe pneumonia: presence of severity criteria (ATS / IDSA), one of two major or three minor criteria.)
• 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.
• Pregnant or lactating women.
• Women of childbearing potential not using an effective contraceptive method (withdrawal, intrauterine device, or oral contraceptives).
• History of severe anaphylactic reaction with the administration of equine plasma.
• Patients with comorbidities that justify a risk of high mortality from causes independent of SARS-CoV-2 infection (eg, stage IV cancer)
• Patient who does not consent to participate.

Sponsors & Collaborators

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

Study Sites (1)

Hospital General de Agudos Donación Francisco J. Santojanni

Buenos Aires, 1408, Argentina

RECRUITING

MeSH Terms

Conditions

COVID-19

Interventions

Immunization, Passive; Control Groups

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Epidemiologic Research Design; Epidemiologic Methods; Research Design; Methods

Study Officials

• Guillermo A Keller, PhD

  INPB - ANLIS Malbrán

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guillermo A Keller, MD PhD

CONTACT

011-4961-0943; gkeller@anlis.gob.ar

Claudio Bonel, PhD

CONTACT

011-4303-1801; cbonel@anlis.gob.ar

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician. Specialist in internal medicine and clinical pharmacology

Model Details: This is an adaptive phase 2/3, randomized, blinded, placebo-controlled study. 200 total patients (ratio 1:1) will be included with intermediate evaluations when reaching the initial 20 patients (initial analysis of safety and pharmacokinetics), 100 (analysis of safety and efficacy) and 200 (final analysis).

Study Record Dates

• First Submitted: June 1, 2021
• First Posted: June 4, 2021
• Study Start: June 1, 2021
• Primary Completion: November 30, 2021
• Study Completion: December 31, 2021
• Last Updated: September 17, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: After completion of the study.
• Access Criteria: By request to the Principal Investigator

Locations

AR (1)