Clinical trial NCT04834089: Clinical Trial for Assessment of Anti-SARS-CoV-2 Serum for Early Treatment of COVID-19 Cases
Official title: Phase I/II Clinical Trial for Dose Escalation and Safety Assessment and Clinical Response of Anti-SARS-CoV-2 Serum Produced by Instituto Butantan
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Immunosuppression
Cancer
COVID-19
Other Complication of Kidney Transplant
Chemotherapy
Renal Disease
Diabetes Mellitus
Cardiovascular Diseases
Chronic Obstructive Pulmonary Disease
Keywords: Anti-SARS-CoV-2 serum
safety
pharmacokinetic
efficacy
Lead sponsor: Butantan Institute
Sponsor class: OTHER_GOV
First posted: 2021-04-06
Enrollment: 618
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model 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.
Primary purpose: TREATMENT

Brief summary: 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

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

.

Eligibility criteria: 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

Primary outcomes:
measure: Frequency of local and systemic adverse events
timeFrame: 12 hours after product administration
measure: Anti-SARS-CoV-2 serum average life
timeFrame: 28 days after product administration
measure: Proportion of patients with change in COVID-19 disease progression profile after administration of anti-SARS-CoV-2 serum
timeFrame: 14 days after product administration
Secondary outcomes:
measure: Frequency of local and systemic adverse events
timeFrame: 28 days after product administration
measure: Frequency of severe adverse events
timeFrame: 28 days after product administration
measure: Clinical response
timeFrame: 14 days after product administration
measure: Symptoms duration
timeFrame: 28 days after product administration
measure: Hospitalization time in Intensive Care Unit
timeFrame: 28 days after product administration
measure: Deaths
timeFrame: 28 days after product administration
Other outcomes:
measure: Frequency and magnitude of equine antibodies titers
timeFrame: 28 days after product administration
measure: Frequency and magnitude of neutralizing antibodies titers Against SARS-CoV-2
timeFrame: 28 days after product administration
measure: Proportion of medical assistance
timeFrame: 14 days after product administration
measure: Proportion of emergency service visit
timeFrame: 14 days after product administration
measure: Proportion of hospitalization
timeFrame: 14 days after product administration
measure: Proportion of patients with change in COVID-19 disease progression
timeFrame: 28 days after product administration
Locations:
city: Sao Paulo
country: Brazil
facility: Hospital do Rim
state: SP
city: São Paulo
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo
Study officials:
affiliation: Butantan Institute
name: Ricardo Palacios, MD, PhD
role: STUDY_DIRECTOR
References: