Clinical Trial for Assessment of Anti-SARS-CoV-2 Serum for Early Treatment of COVID-19 Cases (SOROCOV)

Phase I/II Clinical Trial for Dose Escalation and Safety Assessment and Clinical Response of Anti-SARS-CoV-2 Serum Produced by Instituto Butantan

Phase I/II Randomized Clinical Trial to evaluate the safety, pharmacokinetic and efficacy of Anti-SARS-CoV-2 hyperimmune serum.

The study will include patients at early stage of COVID-19 with increased risk for severe disease due to underlying medical conditions to determine the utility of an equine heterologous serum anti-SARS-CoV-2 to avoid progression to a severe COVID-19

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiovascular Diseases; COVID-19; Diabetes Mellitus; Cancer; Chronic Obstructive Pulmonary Disease; Chemotherapy; Immunosuppression; Renal Disease; Other Complication of Kidney Transplant
• Intervention / Treatment: Biological: AntiSARS-CoV-2 Serum; Other: Placebo

Detailed Description

Phase I/II Clinical Trial, randomized, multicentric, on three stages (A, B and C) to evaluate the safety, pharmacokinetic and efficacy of Anti-SARS-CoV-2 serum and dose escalation.

The study will be in three stages:

Stage A: 30 kidney transplanted participants (very high risk), where 15 will received 1 vial (5 mL) and 15 will received 2 vials (10 mL) of serum;

Stage B: 30 immunocompetent participants with at least 2 risk factors for severe disease (high risk) who will receive the dose selected by stage A;

Stage C: 558 participants, of very high risk and high risk, compared with placebo in allocation 2:1 (endpoint-driven design)

Allocation type Open study without allocation of randomization on Stages A and B Randomized allocation with placebo comparator in Stage C.

Recruitment Status: On planning

Date of 1st recruitment Expected: April 2021

Target sample siz 618 (30/30/538) participants

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• Study Type: Interventional
• Enrollment (Anticipated): 618
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ricardo Palacios, MD, PhD; Phone Number: +551137232121; Email: ricardo.palacios@butantan.gov.br

Study Locations

• Brazil
  • São Paulo, Brazil, 05403-010
    • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
  • SP
    • Sao Paulo, SP, Brazil, 04038-002
      • Hospital do Rim
      • Contact: Jose Osmar Medina Pestana, MD,PhD
      • Principal Investigator: Jose Osmar Medina Pestana, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adults 18 years of age or older;
2. Diagnosis of SARS-CoV-2 infection confirmed by RT-PCR or antigen test no more than 5 days ago;

3. Onset of clinical signs and symptoms of COVID-19 no more than 5 days manifested as:

   1. Presenting sudden onset of anosmia and/or ageusia without any other reasonable explanation and/or;
   2. Thoracic image by radiography, tomography or ultrasonography compatible with acute clinical symptoms findings of COVID-19 and/or;
   3. Acute onset of cough accompanied by fever and/or
   4. Acute onset of three or more of the following symptoms: fever, cough, fatigue or general weakness, headache, myalgia, sore throat, runny nose, dyspnea, anorexia or nausea or vomit, diarrhea and mental status change.
4. Oxygen saturation by pulse oximetry ≥92%
5. Agree to periodic contacts by phone, electronic means and home visits;

6. Demonstrate intention to participate in the study, documented by Informed Consent Form signature on the part of the participant.

   For the very high risk group:

7. Being on continuous drug immunosuppressant more than two weeks due to a basic medical condition (e.g. transplant or cancer);

   For the high risk group:

8. To present at least two risk factors for developing serious COVID-19 (Over 60 years of age; diabetes mellitus; chronic obstructive pulmonary disease; kidney disease; cardiovascular diseases and body mass index ≥ 35).

Exclusion Criteria:

1. Presenting COVID-9 in need of oxygen therapy on the moment of study inclusion, in other words, score 5 or higher in WHO COVID-19 progression scale;
2. Behavioral, cognitive or psychiatric disease that, in principal investigator opinion or his/her medical representative, affect the participant capacity in understanding and collaborating with study protocol requirements;
3. Any use considered alcohol or drugs abuse in the last 12 months prior to study inclusion that caused medical, professional or family problems, as indicated by clinical history;
4. Severe allergic reaction history or anaphylaxis to heterologous serum or product components of the study;
5. To have received heterologous serum or convalescent plasma in the last three months before of study inclusion, or planned administration of hemoderivatives or immunoglobulin on the next 28 days of study inclusion;
6. The participant is a team member who is conducting the study or is in a dependent relationship with one of the study team members. Dependency relationships include close relatives (in other words, sons, partner/spouse, brothers, parents), as well as Researcher staff or staff from the location conducting the study;

7. Any other condition that, in the principal investigator opinion or his/her medical representative, could threaten the safety or rights of a potential participant or which prevents him from fulfilling with this protocol.

   For female:

8. Pregnancy (confirmed by positive β-hCG test), breastfeeding and/or expressing an intention to have sexual practices with reproductive potential without using a contraceptive method within four weeks of the product administration;

   For stages A and B:

9. Previous immunization with vaccine against COVID-19

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental product group (Stage A); Anti-SARS-CoV-2 Serum Dose: 5 mL/dose or 10 mL/dose Administration Route: Intravenous	Biological: AntiSARS-CoV-2 Serum; Stage A: 30 kidney transplanted participants (very high risk), where 15 will received 1 vial (5 mL) and 15 will received 2 vials (10 mL) of serum; Stage B: 30 immunocompetent participants with at least 2 risk factors for severe disease (high risk) who will receive the dose selected by stage A; Stage C: 558 participants, of very high risk and high risk, compared with placebo in allocation 2:1.
Placebo Comparator: Placebo group (Stage C); Saline solution Administration Route: Intravenous	Other: Placebo; Saline solution Administration Route: Intravenous
Experimental: Experimental product group (Stage B); Anti-SARS-CoV-2 Serum Dose: 5 mL/dose or 10 mL/dose Administration Route: Intravenous	Biological: AntiSARS-CoV-2 Serum; Stage A: 30 kidney transplanted participants (very high risk), where 15 will received 1 vial (5 mL) and 15 will received 2 vials (10 mL) of serum; Stage B: 30 immunocompetent participants with at least 2 risk factors for severe disease (high risk) who will receive the dose selected by stage A; Stage C: 558 participants, of very high risk and high risk, compared with placebo in allocation 2:1.
Experimental: Experimental product group (Stage C); Anti-SARS-CoV-2 Serum Dose: 5 mL/dose or 10 mL/dose Administration Route: Intravenous	Biological: AntiSARS-CoV-2 Serum; Stage A: 30 kidney transplanted participants (very high risk), where 15 will received 1 vial (5 mL) and 15 will received 2 vials (10 mL) of serum; Stage B: 30 immunocompetent participants with at least 2 risk factors for severe disease (high risk) who will receive the dose selected by stage A; Stage C: 558 participants, of very high risk and high risk, compared with placebo in allocation 2:1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of local and systemic adverse events	Frequency of local and systemic adverse events, solicited and unsolicited, during the infusion and within 12 hours after administration of the heterologous serum	12 hours after product administration
Anti-SARS-CoV-2 serum average life	Anti-SARS-CoV-2 serum average life measured by equine antibodies levels	28 days after product administration
Proportion of patients with change in COVID-19 disease progression profile after administration of anti-SARS-CoV-2 serum	Proportion of patients with change in COVID-19 disease progression profile after administration of anti-SARS-CoV-2 serum, based on the WHO clinical progression scale (not progression to severe disease requiring mechanical ventilation or death - Score 7 or larger)	14 days after product administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of local and systemic adverse events	Frequency of local and systemic adverse events, solicited and unsolicited, up to 28 days of serum heterologous administration	28 days after product administration
Frequency of severe adverse events	Frequency of severe adverse events and of the special interest up to 28 days after administration of serum heterologous	28 days after product administration
Clinical response	Clinical response according serum anti-SARS-CoV-2 dosage	14 days after product administration
Symptoms duration	Symptoms duration associated to COVID-19	28 days after product administration
Hospitalization time in Intensive Care Unit	Hospitalization time in Intensive Care Unit related to COVID-19	28 days after product administration
Deaths	Frequency of deaths by COVID-19	28 days after product administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and magnitude of equine antibodies titers	Frequency and magnitude of equine antibodies titers 14 and 28 days after administration of anti-SARS-CoV-2 serum	28 days after product administration
Frequency and magnitude of neutralizing antibodies titers Against SARS-CoV-2	Frequency and magnitude of neutralizing antibodies titers Against SARS-CoV-2 after administration of anti-SARS-CoV-2 serum	28 days after product administration
Proportion of medical assistance	Proportion of medical assistance related to COVID-19 (score ≥ 3 of WHO)	14 days after product administration
Proportion of emergency service visit	Proportion of emergency service visit related to COVID-19	14 days after product administration
Proportion of hospitalization	Proportion of hospitalization related to COVID-19 (defined as ≥24 hours of hospital care) (score ≥ 4 of WHO)	14 days after product administration
Proportion of patients with change in COVID-19 disease progression	Proportion of patients with change in COVID-19 disease progression profile after administration of anti-SARS-CoV-2 serum according to underlying medical conditions.	28 days after product administration

Collaborators and Investigators

• Sponsor: Butantan Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2021
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): May 1, 2022

Study Registration Dates

• First Submitted: April 1, 2021
• First Submitted That Met QC Criteria: April 3, 2021
• First Posted (Actual): April 6, 2021

Study Record Updates

• Last Update Posted (Actual): April 8, 2021
• Last Update Submitted That Met QC Criteria: April 5, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: safety; pharmacokinetic; efficacy; Anti-SARS-CoV-2 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; Cardiovascular Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: SAS-01-IB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No