2. Background:
o SARS-COV-2 is estimated to have caused more than 240 million
illnesses & 4.9 million deaths worldwide. Majority of the cases
are in fact asymptomatic or mild-moderate.
o Several monoclonal antibodies have been recently studied
including Bamlanivimab-Etesevimab and then Casirvimab-
Imdevimab cocktail (REGEN-COV).
o Casirvimab and Imdevimab are two antibodies that bind non-
competitively to 2 distinct epitopes of the RBD of the S-protein.
o Phase 1-2 trials of REGEN-COV showed safety, reduction of the
viral load, and the number of related medical visits.
o There is a need to assess using this combination in high-risk
COVID-19 positive outpatients for adverse disease outcomes.
3. Inclusion Criteria:
o 18 yo and above (Adults = Cohort 1)
o SARS-COV-2 positive, by RT-PCR, within 72 hours (Confirmed)
o With any COVID-19 symptom: Fever, Cough, SOB (Symptomatic)
o Symptomatic for no more than 7 days (Early)
4. Exclusion Criteria:
o Hospitalized due to COVID-19
o Hypoxic <93% SpO2
o Participating in a trial involving Convalescent plasma or
Other SARS-COV-2 monoclonal antibodies within 3 months
o Received EUA COVID-19 related treatments within 30 days
o Receiving IVIG for any reason
o Has known allergy to the components of the study drug
o Pregnant or Breastfeeding women (Cohort 3)
5. Methods:
o Type: Randomized Controlled Trial
o Randomization: 1:1:1, Stratified by Country & Risk Factors
o Blinding: Double Blinded
o Place: Multicenter (>80 Centers in USA & Mexico)
o Time: September 2020 – January 2021
o Funding: Regeneron Pharmaceuticals and others
6. Methods:
o Intervention: Identical 1 IV dose of any REGN-COV dose or Placebo
o Initially: Placebo vs REGEN-COV 2.4g vs REGEN-COV 8g
o Phase 2: A) 2.4g = 8g B) Most events occurred in High-Risk
o Amended 11/2020:
A) Placebo vs REGEN-COV 1.2g vs REGEN-COV 2.4g
B) Patients with Zero risk factors were excluded
10. Statistical Analysis:
o Primary Endpoint: % of patients with at least 1 COVID related
Hospitalization OR Death from any cause, by Day 29
o Secondary Endpoints:
A) Same but from Day 4-29
B) Time to resolution of COVID symptoms (0)
o Percentage comparison: Stratified Cochran-Mantel-Haenszel test
o P-value and 95% CI: Farrington-Manning model
o Time to symptoms resolution: Daily Score, then Stratified log-rank
o Median times and associated 95% CI: Kaplan-Meier method
o Hazard-Ratio and associated 95% CI: Cox regression model
o Software: SAS version 9.4
17. Conclusion:
o REGEN-COV reduced the risk of COVID-19 related
Hospitalizations or Death from any cause in high-risk non-
hospitalized SARS-COV-2 positive adults compared to placebo
(Mainly driven by reduction of related Hospitalizations).
o REGEN-COV reduced the time to resolution of symptoms as well.
o REGEN-COV should be considered for this population.
