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

NCT04838821 | Unknown Phase 2 DMC

• 1 other identifier: R020-SABI-00268
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 4

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

Keywords

Covid19; Anti-SARS-CoV-2 hyperimmune equine serum; Neutralizing antibodies; Passive Immunotherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (16)

• Mechanical ventilation assistance (MVA)

  day 28

• Hospital stay

  day 28

• Inflammatory markers IL6

  Days 0, 1, 2, 3, 5, 7, and 14 or discharge

• Inflammatory markers CRP

  Days 0, 1, 2, 3, 5, 7, and 14 or discharge

• Inflammatory markers Procalcitonin

  Days 0, 1, 2, 3, 5, 7, and 14 or discharge

Study Arms (2)

Anti SARS-CoV-2 equine hyperimmune serum

EXPERIMENTAL

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

Placebo

EXPERIMENTAL

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

Interventions

Anti SARS-CoV-2 equine hyperimmune serum 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.

Anti SARS-CoV-2 equine hyperimmune serum

placebo 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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• COVID-19 patients that do not require hospitalization (outpatient setting).
• Patients who are participating in other therapeutic clinical trials.
• COVID-19 patients who have received convalescent plasma treatment.
• Critical disease COVID- 19 patients (respiratory failure, septic shock, and/or multiple organ dysfunction, admission PaO2/FIO2 ratio \< 100).
• Previously snake bitten individuals that received any type of equine hyperimmune serum treatment.
• History of an allergic reaction due to contact or exposure to horses.
• Pregnant or breastfeeding women.
• Patients who, at the investigator´s discretion, are not likely to comply with study indications and procedures.
• Patients currently undergoing hemodialysis in a renal support program.
• 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.

Sponsors & Collaborators

• Caja Costarricense de Seguro Social: lead
• Universidad de Costa Rica: collaborator
• Ministry of Health Costa Rica: collaborator

Study Sites (4)

Centro Especializado de Atención COVID19 (CEACO)

San José, Costa Rica

RECRUITING

Hospital Dr. Rafael Ángel Calderón Guardia

San José, Costa Rica

RECRUITING

Hospital México

San José, Costa Rica

RECRUITING

Hospital San Juan de Dios

San José, Costa Rica

RECRUITING

Related Publications (1)

• 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.

  PMID: 36700518 DERIVED

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 23, 2021
• First Posted: April 9, 2021
• Study Start: March 29, 2021
• Primary Completion: July 29, 2021
• Study Completion: September 29, 2021
• Last Updated: May 21, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

CO (4)