Clinical trial NCT04838821: Efficacy and Safety of Three Different Doses of an Anti SARS-CoV-2 Hyperimmune Equine Serum in COVID-19 Patients
Official title: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Covid19
Keywords: Covid19
Anti-SARS-CoV-2 hyperimmune equine serum
Neutralizing antibodies
Passive Immunotherapy
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: 2021-04-09
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 156 participants will be allocated randomly to either one of three treatment groups or to placebo through an internet based randomizer (Studyrandomizer.com). Participants can withdraw from the study at any time.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Crude Mortality in COVID-19 patients
timeFrame: day 7 and 28
Secondary outcomes:
measure: Mechanical ventilation assistance (MVA)
timeFrame: day 28
measure: Hospital stay
timeFrame: day 28
measure: Inflammatory markers IL6
timeFrame: Days 0, 1, 2, 3, 5, 7, and 14 or discharge
measure: Inflammatory markers CRP
timeFrame: Days 0, 1, 2, 3, 5, 7, and 14 or discharge
measure: Inflammatory markers Procalcitonin
timeFrame: Days 0, 1, 2, 3, 5, 7, and 14 or discharge
measure: Inflammatory markers Ferritin
timeFrame: Days 0, 1, 2, 3, 5, 7, and 14 or discharge
measure: Thrombotic markers PTT
timeFrame: Days 0, 1, 2, 3, 5, 7, and 14 or discharge
measure: Thrombotic markers PT
timeFrame: Days 0, 1, 2, 3, 5, 7, and 14 or discharge
measure: Thrombotic markers D Dimer
timeFrame: Days 0, 1, 2, 3, 5, 7, and 14 or discharge
measure: Thrombotic markers Fibrinogen
timeFrame: Days 0, 1, 2, 3, 5, 7, and 14 or discharge
measure: SpO2/FIO2 ratio
timeFrame: Days 0, 1, 2, 3, 4, 5, 6, 7 and 14 or discharge
measure: Changes in viral load
timeFrame: Days 0, 3, 7
measure: Modified Sequential Organ Failure Assessment (mSOFA)
timeFrame: Time Frame: Days 0, 1, 2, 3, 5, 7 and 14 or discharge
measure: WHO 8 point ordinal scale
timeFrame: Days 0, 1, 2, 3, 4, 5, 6, 7, 14 and 28 or discharge
measure: Anti SARS-CoV-2 antibodies
timeFrame: Days 0, 1, 2, 3, 5, 7 and 14 or discharge
measure: Adverse events
timeFrame: day 28
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:
References: