Clinical trial NCT04610502: Efficacy and Safety of Two Hyperimmune Equine Anti Sars-CoV-2 Serum in COVID-19 Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
Keywords: COVID-19
Anti-SARS-CoV-2 Equine Immunoglobulin
Passive Immunotherapy
Neutralizing Equine Antibodies.
Lead sponsor: Caja Costarricense de Seguro Social
Sponsor class: OTHER_GOV
Collaborators: name: Universidad de Costa Rica
name: Ministry of Health Costa Rica
First posted: 2020-10-30
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: To evaluate the efficacy and safety of two formulations of equine anti-SARS-CoV-2 immunoglobulins ("S" and "M").
timeFrame: 2,3,4,5,7,10,14 Days
measure: To evaluate safety of two formulations of equine anti-SARS-CoV-2 immunoglobulins ("S" and "M").
timeFrame: 3 months
Secondary outcomes:
measure: Viral load
timeFrame: Days 2,3,4,5,7,10,14
measure: Mortality
timeFrame: days 14, 24
measure: Hospital stay
timeFrame: Day 14, 24
measure: ventilatory support
timeFrame: Day 24
measure: blood levels of immunoglobulins against SARS-CoV-2
timeFrame: Days 2,3,4,5,7,10,14
measure: inflammatory markers
timeFrame: day 10
measure: thrombotic marker levels
timeFrame: days 2, 3, 4, 7, 10, and 14
measure: negativization period of RT-PCR on nasopharyngeal swabbing (Reverse transcription polymerase chain reaction)
timeFrame: 1 month
measure: SpFI (Partial saturation Oxigen/inspired fraction of Oxigen) gain
timeFrame: Days 2,3,4,5,7,10,14
measure: Lung Ultrasound
timeFrame: days 3,10
measure: Adverse events
timeFrame: days 2,3,4,5,6,7,10,14,24
Other outcomes:
Locations:
city: San José
country: Costa Rica
facility: Centro Especializado de Atención COVID19 (CEACO)
city: San José
country: Costa Rica
facility: Hospital Dr. Rafael Ángel Calderón Guardia
city: San José
country: Costa Rica
facility: Hospital México
city: San José
country: Costa Rica
facility: Hospital San Juan de Dios
Study officials:
affiliation: Caja Costarricense de Seguro Social
name: Alfredo Sanabria, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UCR
name: Willem Bujan, MBA
role: STUDY_CHAIR
References: