Clinical trial NCT04913779: Safety and Effectiveness of an Immunobiological Drug in CoViD-19
Official title: Study to Evaluate the Safety and Effectiveness of an Immunobiological Drug (Anti SARS-CoV-2) in the Treatment of Coronavirus Disease 2019 (CoViD-19)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: COVID-19 Pneumonia
COVID-19 Respiratory Infection
Covid19
Keywords: Anti-SARS-CoV-2
Purified F(ab')2 Fragments
Passive immunotherapy
Equine Serum
Lead sponsor: Administracion Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran
Sponsor class: OTHER_GOV
First posted: 2021-06-04
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in time needed to clinical improvement
timeFrame: Reached each day between day 1 and 28 post-inclusion in the study
Secondary outcomes:
measure: Change in the number of patients in each World Health Organization (WHO) Ordinal Scale Category (0 to 8 being 0 better and 8 worse)
timeFrame: days 7, 14 and 21 post-inclusion
measure: Change in Mortality rate
timeFrame: 28 days post-inclusion
measure: Change in Mechanical Ventilation Requirement rate
timeFrame: 28 days post-inclusion
measure: Change in duration of oxygen treatment requirement
timeFrame: 28 days post-inclusion
measure: Change in Length of Hospitalization
timeFrame: 28 days post-inclusion
measure: Change in frequency of nosocomial infection
timeFrame: 28 days post-inclusion
measure: Change in Lymphocyte cell count
timeFrame: 28 days post-inclusion
measure: Change in viral RNA Negativization rate on nasopharyngeal swab test
timeFrame: 7, 14, 21, and 28 days post-inclusion
measure: Description of adverse events type and frequency
timeFrame: 28 days post-inclusion
measure: Requirement of additional treatments for Adverse Drug reactions
timeFrame: 28 days post-inclusion
measure: Describe the AUC of purified F(ab')2 Anti-SARS-CoV-2
timeFrame: Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days
measure: Describe the Cmax of purified F(ab')2 Anti-SARS-CoV-2
timeFrame: Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days
measure: Describe the t1/2 of purified F(ab')2 Anti-SARS-CoV-2
timeFrame: Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days
measure: Describe the Ke of purified F(ab')2 Anti-SARS-CoV-2
timeFrame: Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days
Other outcomes:
Locations:
city: Ciudad Autónoma De Buenos Aires
country: Argentina
facility: Hospital General de Agudos Donación Francisco J. Santojanni
Study officials:
affiliation: INPB - ANLIS Malbrán
name: Guillermo A Keller, PhD
role: PRINCIPAL_INVESTIGATOR
References: