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

NCT04610502 | Completed Phase 2 DMC

• 1 other identifier: R020-SABI-00259
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 4

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.

Conditions

Covid19

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• Viral load

  Days 2,3,4,5,7,10,14

• Mortality

  days 14, 24

• Hospital stay

  Day 14, 24

• ventilatory support

  Day 24

• blood levels of immunoglobulins against SARS-CoV-2

  Days 2,3,4,5,7,10,14

Study Arms (2)

Equine immunoglobulin anti SARS-CoV-2 formulation S

EXPERIMENTAL

Experimental equine Imunoglobulins antiSARSCov" Formuation S

Biological: Administration of Equine immunoglobulin anti SARS-CoV-2

Equine immunoglobulin anti SARS-CoV-2 formulation M

EXPERIMENTAL

Experimental equine Imunoglobulins antiSARSCov" Formuation M

Biological: Administration of Equine immunoglobulin anti SARS-CoV-2

Interventions

Administration of Equine immunoglobulin anti SARS-CoV-2 BIOLOGICAL

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.

Equine immunoglobulin anti SARS-CoV-2 formulation M; Equine immunoglobulin anti SARS-CoV-2 formulation S

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Caja Costarricense de Seguro Social: lead
• Universidad de Costa Rica: collaborator
• Ministry of Health Costa Rica: collaborator

Study Sites (4)

Centro Especializado de Atención COVID19 (CEACO)

San José, Costa Rica

Location

Hospital Dr. Rafael Ángel Calderón Guardia

San José, Costa Rica

Location

Hospital México

San José, Costa Rica

Location

Hospital San Juan de Dios

San José, Costa Rica

Location

MeSH Terms

Conditions

COVID-19

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

Study Officials

• Alfredo Sanabria, PhD

  Caja Costarricense de Seguro Social

  PRINCIPAL INVESTIGATOR

• Willem Bujan, MBA

  UCR

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2020
• First Posted: October 30, 2020
• Study Start: September 6, 2020
• Primary Completion: October 6, 2020
• Study Completion: December 6, 2020
• Last Updated: March 19, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

CO (4)