Efficacy and Safety of Two Hyperimmune Equine Anti Sars-CoV-2 Serum in COVID-19 Patients (SECR-01)

Randomized, Controlled, Double-blind, Multicenter Clinical Study to Compare the Efficacy and Safety of the Administration of Two Hyperimmune Equine Anti-Sars-CoV-2 ("S" and "M") Serum Formulations in Hospitalized Patients With COVID-19

Reports of the use of plasma from convalescent patients and purified immunoglobulin preparations in respiratory infections by various viral agents and SARS-CoV-2 in severely ill patients suggest that specific neutralizing antibodies may benefit their clinical course. During the previous SARS-CoV epidemic in 2003, preparations of hyperimmune equine serum were produced and demonstrated in vitro viral neutralization. These preparations were also successful in several animal models. Taking advantage of the important trajectory of our country in the study and use of equine hyperimmune serums with neutralizing antibodies for snake venom, preparations of hyperimmune serums against recombinant proteins of SARS-CoV-2 were produced through repeated immunization of horses, a first group of animals was inoculated with the "S" (Spike) protein of the virus and the second group with a mixture "M" of the S1 (Spike) proteins, the N (Nucleoprotein) protein and a construct with epitopes of the S1, E (Envelope) and M (Membrane) proteins, generating two different pharmaceutical preparations.

Objective: Evaluate the efficacy and safety of two hyperimmune equine serum anti-Sars-CoV-2 ("S" and "M") formulations as an addition to the standard therapeutic approach for hospitalized patients with COVID-19 over 18 years of age with the presence of at least 2 risk factors and a symptom onset period not exceeding 10 days.

A total of 52 patients will be included and randomly divided into two balanced groups. On day 1, all participants from each group will receive an intravenous infusion containing 10ml (one vial) of hyperimmune equine anti-Sars-CoV-2 serum labeled as A or B.

Patients will be evaluated clinically, general laboratory, SARS-CoV-2 serologies, SARS-CoV-2 viral load and cytokines level as well as pulmonary ultrasound. Data will be collected for both groups on Days 0 to 7, 10 and 14 or discharge after completion of treatment. The study will end for each participant on the day of discharge from the hospital.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Biological: Administration of Equine immunoglobulin anti SARS-CoV-2

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Costa Rica
  • San José, Costa Rica
    • Centro Especializado de Atención COVID19 (CEACO)
  • San José, Costa Rica
    • Hospital Dr. Rafael Ángel Calderón Guardia
  • San José, Costa Rica
    • Hospital México
  • San José, Costa Rica
    • Hospital San Juan de Dios

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Agreement to participate in the study by signing the prior informed consent.
• Age over 18 years.
• Inpatient with RT-PCR confirmation of SARS-CoV-2.
• Period of onset of symptoms related to COVID-19 not greater than 10 days
• Presence of at least 2 documented risk factors
• Moderate and severe clinical presentation of the disease.

Exclusion Criteria:

• Patients who did not sign the Informed Consent.
• Critical patient.
• Patient previously bitten by a snake that was treated with equine hyperimmune serum.
• Patients with COVID-19 on an outpatient basis.
• Pregnant women.
• Patients in Hemodialysis program.
• Patients who have already received plasma from a convalescent COVID-19 patient.
• Patients who were classified prior to the diagnosis of COVID-19 by the treating physician as having a reserved prognosis with a short lifespan.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Equine immunoglobulin anti SARS-CoV-2 formulation S; Experimental equine Imunoglobulins antiSARSCov" Formuation S	Biological: Administration of Equine immunoglobulin anti SARS-CoV-2; The participants will receive premedication with Acetaminophen 500mg PO, Cimetidine300mg IV and Chlortrimeton 10mg IV. Then the investigators will do the Administration of Equine Imunoglobulin anti SARS Cov 2 on day 1 a vial of 10ml of the drug during 1 hour Intravenously. Then the hospitalized participants will be followed until they are discharged.
Experimental: Equine immunoglobulin anti SARS-CoV-2 formulation M; Experimental equine Imunoglobulins antiSARSCov" Formuation M	Biological: Administration of Equine immunoglobulin anti SARS-CoV-2; The participants will receive premedication with Acetaminophen 500mg PO, Cimetidine300mg IV and Chlortrimeton 10mg IV. Then the investigators will do the Administration of Equine Imunoglobulin anti SARS Cov 2 on day 1 a vial of 10ml of the drug during 1 hour Intravenously. Then the hospitalized participants will be followed until they are discharged.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the efficacy and safety of two formulations of equine anti-SARS-CoV-2 immunoglobulins ("S" and "M").	Change in clinical status (days requiring supplemental oxygen) between the two treatment groups.	2,3,4,5,7,10,14 Days
To evaluate safety of two formulations of equine anti-SARS-CoV-2 immunoglobulins ("S" and "M").	To identify the adverse effects of anti-Sars-CoV-2 type "S" or type "M" equine immunoglobulins administered to patients diagnosed as SARS-CoV-2 positive, with the presence of at least 2 risk factors and a symptom onset period of no more than 10 days.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral load	Change of viral load (number of copies of SARS Cov2 per ml)	Days 2,3,4,5,7,10,14
Mortality	Change in mortality between the two treatment groups.	days 14, 24
Hospital stay	Change in the overall hospital stay of patients between the two treatment groups.	Day 14, 24
ventilatory support	Change in duration of ventilation support in the two treatment groups	Day 24
blood levels of immunoglobulins against SARS-CoV-2	Change in titer of immunoglobulins blood levels (UA/ml) against SARS-CoV-2 between the two treatment groups.	Days 2,3,4,5,7,10,14
inflammatory markers	Rate of virologic clearance by nasopharyngeal swab at day 10	day 10
thrombotic marker levels	7. Difference in the decrease of thrombotic marker levels (D-dimer, fibrinogen, prothrombin time, TTP) on study days 2, 3, 4, 7, 10, and 14 or at discharge between the two treatment groups	days 2, 3, 4, 7, 10, and 14
negativization period of RT-PCR on nasopharyngeal swabbing (Reverse transcription polymerase chain reaction)	8. Difference in the number of days elapsed between two negative determinations separated by at least 24 hours in the COVID-19 test by RT-PCR on nasopharyngeal swabbing between the two treatment groups	1 month
SpFI (Partial saturation Oxigen/inspired fraction of Oxigen) gain	Improvement in SAFI (SatO2/FiO2) between the two treatment groups.	Days 2,3,4,5,7,10,14
Lung Ultrasound	Change in POCUS score between the two treatment groups. (Minimum: 0 = normal; Maximum: 32= Multiple Lungs Consolidations).	days 3,10
Adverse events	Number of adverse events as measured by CTCAE v. 5.0 between the two groups	days 2,3,4,5,6,7,10,14,24

Collaborators and Investigators

• Sponsor: Caja Costarricense de Seguro Social
• Collaborators: Universidad de Costa Rica; Ministry of Health Costa Rica
• Investigators: Principal Investigator: Alfredo Sanabria, PhD, Caja Costarricense de Seguro Social; Study Chair: Willem Bujan, MBA, UCR

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2020
• Primary Completion (Actual): October 6, 2020
• Study Completion (Actual): December 6, 2020

Study Registration Dates

• First Submitted: September 15, 2020
• First Submitted That Met QC Criteria: October 29, 2020
• First Posted (Actual): October 30, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2021
• Last Update Submitted That Met QC Criteria: March 18, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; Anti-SARS-CoV-2 Equine Immunoglobulin; Passive Immunotherapy; Neutralizing Equine Antibodies.
• 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; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous
• Other Study ID Numbers: R020-SABI-00259

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