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

Covid19 Clinical Trial

— SECR-01  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04610502
• Other study ID #: R020-SABI-00259
• Status: Completed
• Phase: Phase 2
• Start date: September 6, 2020
• Est. completion date: December 6, 2020

Study information

• Verified date: March 2021
• Source: Caja Costarricense de Seguro Social
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: December 6, 2020
• Est. primary completion date: October 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Covid19

Intervention

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.

Locations

Country	Name	City	State
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

Sponsors (3)

Lead Sponsor	Collaborator
Caja Costarricense de Seguro Social	Ministry of Health Costa Rica, Universidad de Costa Rica

Country where clinical trial is conducted

Costa Rica, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Viral load	Change of viral load (number of copies of SARS Cov2 per ml)	Days 2,3,4,5,7,10,14
Secondary	Mortality	Change in mortality between the two treatment groups.	days 14, 24
Secondary	Hospital stay	Change in the overall hospital stay of patients between the two treatment groups.	Day 14, 24
Secondary	ventilatory support	Change in duration of ventilation support in the two treatment groups	Day 24
Secondary	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
Secondary	inflammatory markers	Rate of virologic clearance by nasopharyngeal swab at day 10	day 10
Secondary	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
Secondary	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
Secondary	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
Secondary	Lung Ultrasound	Change in POCUS score between the two treatment groups. (Minimum: 0 = normal; Maximum: 32= Multiple Lungs Consolidations).	days 3,10
Secondary	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