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

NCT ID: NCT04838821

Last Updated: 2021-05-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-29
• Study Completion Date: 2021-09-29

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.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Anti SARS-CoV-2 equine hyperimmune serum

Intervention Type: BIOLOGICAL

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.

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.

Group Type: EXPERIMENTAL

placebo

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universidad de Costa Rica

OTHER

Sponsor Role: collaborator

Ministry of Health Costa Rica

UNKNOWN

Sponsor Role: collaborator

Caja Costarricense de Seguro Social

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Centro Especializado de Atención COVID19 (CEACO)

San José, , Costa Rica

Site Status: RECRUITING

Hospital Dr. Rafael Ángel Calderón Guardia

San José, , Costa Rica

Site Status: RECRUITING

Hospital México

San José, , Costa Rica

Site Status: RECRUITING

Hospital San Juan de Dios

San José, , Costa Rica

Site Status: RECRUITING

Countries

Costa Rica

Facility Contacts

Rodrigo Aguilar, MD

Role: primary

raguilart@ccss.sa.cr

22328233

Taciano Lemos, MD

Role: primary

tlemosp@ccss.sa.cr

21014837

Douglas Montero, MD

Role: primary

dmontero@ccss.sa.cr

21047555

Ileana Balmaceda, MD

Role: primary

ibalmace@ccss.sa.cr

25478000

Mario Sibaja, MD

Role: backup

References

Kimber C, Valk SJ, Chai KL, Piechotta V, Iannizzi C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Estcourt LJ, Skoetz N. Hyperimmune immunoglobulin for people with COVID-19. Cochrane Database Syst Rev. 2023 Jan 26;1(1):CD015167. doi: 10.1002/14651858.CD015167.pub2.

Reference Type: DERIVED

PMID: 36700518 (View on PubMed)

Other Identifiers

R020-SABI-00268

Identifier Type: -

Identifier Source: org_study_id