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

• ClinicalTrials.gov Identifier: NCT04610502
• Recruitment Status: Completed
• First Posted: October 30, 2020
• Last Update Posted: March 19, 2021
• Sponsor: Caja Costarricense de Seguro Social
• Collaborators: Universidad de Costa Rica; Ministry of Health Costa Rica
• Information provided by (Responsible Party): Caja Costarricense de Seguro Social

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Covid19	Biological: Administration of Equine immunoglobulin anti SARS-CoV-2	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: September 6, 2020
• Actual Primary Completion Date: October 6, 2020
• Actual Study Completion Date: December 6, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. To evaluate the efficacy and safety of two formulations of equine anti-SARS-CoV-2 immunoglobulins ("S" and "M"). [ Time Frame: 2,3,4,5,7,10,14 Days ]
   Change in clinical status (days requiring supplemental oxygen) between the two treatment groups.
2. To evaluate safety of two formulations of equine anti-SARS-CoV-2 immunoglobulins ("S" and "M"). [ Time Frame: 3 months ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

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

San José, Costa Rica

Sponsors and Collaborators

Caja Costarricense de Seguro Social

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

More Information

• Responsible Party: Caja Costarricense de Seguro Social
• ClinicalTrials.gov Identifier: NCT04610502
• Other Study ID Numbers: R020-SABI-00259
• First Posted: October 30, 2020
• Last Update Posted: March 19, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Caja Costarricense de Seguro Social:

COVID-19; Anti-SARS-CoV-2 Equine Immunoglobulin; Passive Immunotherapy; Neutralizing Equine Antibodies.

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Immunoglobulins; Immunoglobulins, Intravenous; Antibodies; Immunologic Factors; Physiological Effects of Drugs