Efficacy and Safety of Three Different Doses of an Anti SARS-CoV-2 Hyperimmune Equine Serum in COVID-19 Patients (SECR-02)

Randomized, Placebo-controlled, Double-blind, Multicenter Clinical Study to Compare the Efficacy and Safety of the Administration of Three Different Doses of an Anti-SARS-CoV-2 Hyperimmune Equine Serum Formulation in Hospitalized COVID-19 Patients (SECR-02)

Passive immunotherapy is a therapeutic alternative used in a variety of infectious diseases including COVID-19. Equine polyclonal hyperimmune sera is a source of neutralizing antibodies against SARS-CoV-2 and a therapeutic alternative under investigation in COVID-19 patients. In the previous study NCT04610502 no significant variations were observed regarding efficacy and safety between two different pharmaceutical preparations of equine hyperimmune sera and adequate tolerability was reported with both investigational products. Formulations were produced through repeated immunization with viral recombinant proteins and contain either antibodies against SARS-CoV-2 S1 protein (S type) or a combination of viral proteins that included S1, N (nuclear), E (envelop) and M (membrane) (M type). Another investigation (NCT04494984) found that the administration of a pharmaceutical preparation similar to the S type produced clinical improvement in hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

Aim: Evaluate the efficacy and safety of three different doses of an anti-SARS-CoV-2 hyperimmune equine serum formulation (S-type) as an addition to the standard therapeutic approach in adult hospitalized patients with a diagnosis of moderate or severe COVID-19, radiological findings consistent with pneumonia and a symptom onset period not exceeding 10 days.

A total of 156 patients will be included and randomly divided into four groups, each group will receive a different dose of the investigational drug. On day 1, all participants will receive a single intravenous infusion containing the specified dose according to their assigned group. Clinical assessments, laboratory determinations that include: viral load, antibodies quantification, inflammatory and coagulation markers, cytokines levels as well as standard evaluations will be performed for each patient. Data will be collected for all groups on Days 0 to 7, 14 and 28 or at discharge after completion of treatment. The study will end for each participant on the day of discharge from the hospital.

Study Overview

• Status: Recruiting
• Conditions: Covid19
• Intervention / Treatment: Biological: Anti SARS-CoV-2 equine hyperimmune serum; Biological: placebo

• Study Type: Interventional
• Enrollment (Anticipated): 156
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Costa Rica
  • San José, Costa Rica
    • Recruiting
    • Centro Especializado de Atención COVID19 (CEACO)
    • Contact: Rodrigo Aguilar, MD; Phone Number: 22328233; Email: raguilart@ccss.sa.cr
    • Sub-Investigator: José Acuña, MD
  • San José, Costa Rica
    • Recruiting
    • Hospital Dr. Rafael Ángel Calderón Guardia
    • Contact: Taciano Lemos, MD; Phone Number: 21014837; Email: tlemosp@ccss.sa.cr
    • Sub-Investigator: Jose Pablo Madrigal, MD
  • San José, Costa Rica
    • Recruiting
    • Hospital México
    • Contact: Douglas Montero, MD; Phone Number: 21047555; Email: dmontero@ccss.sa.cr
    • Sub-Investigator: Henry Chan, MD
  • San José, Costa Rica
    • Recruiting
    • Hospital San Juan de Dios
    • Contact: Ileana Balmaceda, MD; Phone Number: 25478000; Email: ibalmace@ccss.sa.cr
    • Contact: Mario Sibaja, MD
    • Sub-Investigator: Juan Ignacio Silesky, MSc
    • Sub-Investigator: Ann Echeverri, MD
    • Sub-Investigator: Mario Sibaja, MD

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:

1. Subjects male or female, aged 18 and over.
2. Acceptance to participate in the study by the signature of the informed consent by the subject or relative (if applicable).
3. SARS-CoV-2 infection confirmed by reverse transcriptase -polymerase chain reaction (RT-PCR).
4. SARS-CoV-2 pneumonia confirmed by chest X-ray.
5. Patients with moderate or severe disease clinical presentation of the disease that require hospitalization.
6. Being within 10 days of the initial COVID-19 related symptoms onset.
7. Admission in the participating center within a 24hour period.
8. Female patients of child-bearing age with a negative pregnancy test.

Exclusion Criteria:

1. COVID-19 patients that do not require hospitalization (outpatient setting).
2. Patients who are participating in other therapeutic clinical trials.
3. COVID-19 patients who have received convalescent plasma treatment.
4. Critical disease COVID- 19 patients (respiratory failure, septic shock, and/or multiple organ dysfunction, admission PaO2/FIO2 ratio < 100).
5. Previously snake bitten individuals that received any type of equine hyperimmune serum treatment.
6. History of an allergic reaction due to contact or exposure to horses.
7. Pregnant or breastfeeding women.
8. Patients who, at the investigator´s discretion, are not likely to comply with study indications and procedures.
9. Patients currently undergoing hemodialysis in a renal support program.
10. Individuals who were previously classified by their treating physicians (prior to the COVID-19 diagnosis), of having an unfavorable prognosis with a short lifespan due to a concomitant disease other than the study disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Anti SARS-CoV-2 equine hyperimmune serum; All participants in the treatment groups will receive a single intravenous infusion on day 1 containing the specified dose according to their assigned group 12mg/kg, 30 mg/kg or 56mg/kg. Total volume of the infusion is 180ml, to be administered during a time period of at least 1 hour. Study participants will be followed during their hospitalization until they are discharged and on Study Day 28.	Biological: Anti SARS-CoV-2 equine hyperimmune serum; All participants in the treatment groups will receive a single intravenous infusion on day 1 containing the specified dose according to their assigned group 12mg/kg, 30 mg/kg or 56mg/kg. Total volume of the infusion is 180ml, to be administered during a time period of at least 1 hour. Study participants will be followed during their hospitalization until they are discharged and on Study Day 28.
EXPERIMENTAL: Placebo; All participants in the placebo group will receive a single intravenous infusion on day 1 containing a specified volume of a saline IV solution preparation. Total volume of the infusion is 180ml, to be administered during a time period of at least 1 hour. Study participants will be followed during their hospitalization until they are discharged and on Study Day 28.	Biological: placebo; All participants in the placebo group will receive a single intravenous infusion on day 1 containing a specified volume of a saline IV solution preparation. Total volume of the infusion is 180ml, to be administered during a time period of at least 1 hour. Study participants will be followed during their hospitalization until they are discharged and on Study Day 28.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Crude Mortality in COVID-19 patients	The primary endpoint will be the difference in the proportion of deaths from all causes at 7 and 28 days after the administration of the investigational product between the study groups.	day 7 and 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mechanical ventilation assistance (MVA)	Change in MVA requirement days between study groups at day 28.	day 28
Hospital stay	Change in the overall in-hospital at day 28 stay between study groups.	day 28
Inflammatory markers IL6	Changes in IL-6 levels to be evaluated at days 0, 1, 2, 3, 5, 7, 14 or at time of discharge between study groups.	Days 0, 1, 2, 3, 5, 7, and 14 or discharge
Inflammatory markers CRP	Change in CRP levels to be evaluated at days 0, 1, 2, 3, 5, 7, 14 or at time of discharge between study groups.	Days 0, 1, 2, 3, 5, 7, and 14 or discharge
Inflammatory markers Procalcitonin	Change in procalcitonin levels to be evaluated at days 0, 1, 2, 3, 5, 7, 14 or at time of discharge between study groups.	Days 0, 1, 2, 3, 5, 7, and 14 or discharge
Inflammatory markers Ferritin	Change in ferritin levels to be evaluated at days 0, 1, 2, 3, 5, 7, 14 or at time of discharge between study groups.	Days 0, 1, 2, 3, 5, 7, and 14 or discharge
Thrombotic markers PTT	Changes in PTT levels to evaluated at days 0, 1, 2, 3, 5, 7, 14 or at time of discharge between study groups.	Days 0, 1, 2, 3, 5, 7, and 14 or discharge
Thrombotic markers PT	Changes in PT levels to evaluated at days 0, 1, 2, 3, 5, 7, 14 or at time of discharge between study groups.	Days 0, 1, 2, 3, 5, 7, and 14 or discharge
Thrombotic markers D Dimer	Changes in D Dimer levels to evaluated at days 0, 1, 2, 3, 5, 7, 14 or at time of discharge between study groups.	Days 0, 1, 2, 3, 5, 7, and 14 or discharge
Thrombotic markers Fibrinogen	Changes in Fibrinogen levels to evaluated at days 0, 1, 2, 3, 5, 7, 14 or at time of discharge between study groups.	Days 0, 1, 2, 3, 5, 7, and 14 or discharge
SpO2/FIO2 ratio	Change in the SpO2/FIO2 ratio to evaluated at days 0, 1, 2, 3, 4, 5, 6, 7 and 14 or at time of discharge between study groups	Days 0, 1, 2, 3, 4, 5, 6, 7 and 14 or discharge
Changes in viral load	Change in viral load from baseline to 3 and 7 days after the start of the treatment between study groups	Days 0, 3, 7
Modified Sequential Organ Failure Assessment (mSOFA)	Change in the mSOFA score to evaluated at days 0, 1, 2, 3, 5, 7 and 14 or at time of discharge between study groups.	Time Frame: Days 0, 1, 2, 3, 5, 7 and 14 or discharge
WHO 8 point ordinal scale	Change in the WHO 8 point ordinal scale of clinical status to evaluated at days 0, 1, 2, 3, 4, 5, 6, 7, 14 and 28 or at time of discharge between study groups.	Days 0, 1, 2, 3, 4, 5, 6, 7, 14 and 28 or discharge
Anti SARS-CoV-2 antibodies	Change in the anti SARS-CoV-2 antibodies titer levels to evaluated at days 0, 1, 2, 3, 5, 7 and 14 or at time of discharge between study groups.	Days 0, 1, 2, 3, 5, 7 and 14 or discharge
Adverse events	Incidence of adverse events as measured by CTCAE v. 5.0 at day 28 between study groups.	day 28

Collaborators and Investigators

• Sponsor: Caja Costarricense de Seguro Social
• Collaborators: Universidad de Costa Rica; Ministry of Health Costa Rica

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 29, 2021
• Primary Completion (ANTICIPATED): July 29, 2021
• Study Completion (ANTICIPATED): September 29, 2021

Study Registration Dates

• First Submitted: March 23, 2021
• First Submitted That Met QC Criteria: April 7, 2021
• First Posted (ACTUAL): April 9, 2021

Study Record Updates

• Last Update Posted (ACTUAL): May 21, 2021
• Last Update Submitted That Met QC Criteria: May 20, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Covid19; Neutralizing antibodies; Passive Immunotherapy; Anti-SARS-CoV-2 hyperimmune equine serum
• 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
• Other Study ID Numbers: R020-SABI-00268

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