►Last Update: 3rd April 2020
Completed Trials
HCQ in Mild to Moderate COVID-19 Pneumonia
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Parallel assignment blinded RCT (n = 62)
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Single center, China
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Admitted to general hospital ward with mild to moderate disease (P/F > 300)
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Groups
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Arm 1: HCQ 200 mg BID x 5 days
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Arm 2: Standard Care (including antiviral, systemic steroids). No placebo.
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Results
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Improved time to clinical recovery (TTCR) by 1 day, defined as improvement in pulmonary symptoms (including objective cough frequency), resorption of pneumonic infiltrates on lung CT, and defervescence
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Decreased risk of progression to severe illness
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Conclusions: Provides stronger RCT evidence of the efficacy of HCQ in mild to moderate COVID-19, additive to antiviral therapy.
Preliminary Report: Convalescent Plasma in Critically Ill COVID-19 Patients
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High impact case series (n = 5)
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Single center, China
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All 5 subjects had severe ARDS on mechanical ventilation (2 - 11 days) and had been treated with systemic steroids and antivirals prior to plasma infusion
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Groups
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Arm: Cross-matched convalescent plasma from COVID-19 survivors containing > 1:1000 total anti-SARS-CoV-2 IgG titre and > 1:40 neutralizing titre. 400 mL infused immediately after apheresis.
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Results
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Improved oxygenation, defervescence, roughly 50% improvment in SOFA within 7 days
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3/5 liberated from vent and discharged within 2 weeks
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Reduced viral load
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No comparator group, but outcomes better than historical controls
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Conclusions: Established a foundation for further controlled testing of convaslescent hyperimmune plasma for severe COVID-19
Azithromycin and HCQ for COVID-19 (Gautret Study)
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Non-randomized pragmatic intervention trial (n = 36)
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Multicenter, France
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Groups
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Arm 1: HCQ 600 mg QD x 10 days
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Arm 2: Add on Azithromycin (Z-pak dosing) at clinician discretion to prevent bacterial superinfection
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Arm 3: Nocebo
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Results
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HCQ + Azithromycin resulted in fastest rate of virological cure (clearance of nasopharyngeal viral load)
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No data on safety or adverse effects reported
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Conclusions
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Reinforced the foundation for further testing of HCQ in a rigorous yet pragmatic RCT formal
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HC-nCOV: A Pilot Study of HCQ for "Common" COVID-19 Pneumonia
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RCT parallel assignment (n = 30)
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Single center, China
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Patients admitted to hospital with moderate COVID-19 disease
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Groups
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Arm 1: HCQ 400 mg QD x 5 days
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Arm 2: Placebo
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Results
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1° Outcomes
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No difference in illness severity
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No difference in rate of virological clearance
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No difference in rate of adverse events
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Conclusion: Negative but underpowered study, therefore inconclusive. Creates equipoise for rigorous RCT in a larger and potentially sicker patient population.
Lopinavir-Ritonavir for Adults Hospitalized with Severe COVID-19
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1:1 RCT (n = 199)
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Multisite, China
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Patients were not critically ill. 75% required conventional oxygen NC therapy alone, and only 15% were enrolled from ICU.
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Groups
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Arm 1: Lopinavir-Ritonavir (400-100 mg PO) BID x 14 days
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Arm 2: Placebo
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Results
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1° Outcomes
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No change in 28-day all cause mortality
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Median time to clinical improvement was 1 day shorter in Lopinavir-Ritonavir group
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No change in virological cure
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Conclusion:
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Lopinavir-Ritonavir is not beneficial in hospitalized patients who are not critically ill with COVID-19. Benefit may be seen in more severe illness.
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Recruiting Trials
CloroCOVID19: Chloroquine for SARS-COV-2 ARDS
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Rationale: Chloroquine inhibits endosomal acification and interrupts trafficking of viral proteins
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RCT parallel assignment (n = 440)
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Multicenter, Phase 2, Brazil
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Groups
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Arm 1: Low dose CQ 450 mg BID x 5 days
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Arm 2: High dose CQ 600 mg BID x 10 days
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1°: 28 day all-cause mortality
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Results: RECRUITING
TOCIVID-19: Tocilizumab in COVID-19 Pneumonia (NCI Naples)
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Rationale: IL-6 signaling plays a central role in COVID19-associated cytokine activation syndrome
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Single group interventional trial (n = 330)
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Multicenter, Phase 2, Italy
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Groups
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Arm 1: Tocilizumab 8 mg/kg IV q12 x 2 doses
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Arm 2: Parallel observational cohort
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1°: 30 day all-cause mortality
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Results: RECRUITING
Sarilumab in Hospitalized Patients with COVID-19 (Regeneron)
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Rationale: IL-6 signaling plays a central role in COVID19-associated cytokine activation syndrome
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Adaptive RCT parallel assignment (n = 400)
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Multisite, Phase 2/3, New York
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Groups
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Arm 1: Sarilumab (low dose)
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Arm 2: Sarilumab (high dose)
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Arm 3: Placebo
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1°: Time to clinical improvement
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Results: RECRUITING
ACTT: Adaptive COVID-19 Treatment Trial (NIH/NIAID) of Remdesivir (RDV)
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Rationale: RDV (GS-5734) is a broadly acting viral RNA polymerase inhibitor with promising antiviral activity against SARS-COV-2 in vitro
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RCT parallel assignment (n = 440)
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Multicenter, Phase 3, USA
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Groups
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Arm 1: RDV (200 mg day 1 + 100 mg days 2 - 10)
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Arm 2: Placebo
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1°: Clinical improvement (8-item ordinal scale)
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Results: RECRUITING
Remdesivir in Severe COVID-19 (Gilead) - Study A
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RCT parallel assignment (n = 400)
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Multicenter, Phase 3, USA
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Groups
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Arm 1: RDV IV (200 mg day 1 + 100 mg days 2-5)
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Arm 2: RDV (200 mg day 1 + 100 mg days 2-10)
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1°: Resolution of fever and hypoxemia
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Results: RECRUITING
Remdesivir in Severe COVID-19 (Gilead) - Study B
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RCT parallel assigment
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Multicenter, Phase 3, USA
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Groups:
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Arm 1: RDV IV (200 mg day 1 + 100 mg days 2-5)
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Arm 2: RDV (200 mg day 1 + 100 mg days 2-10)
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Arm 3: Placebo
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1°: Successful discharge at 14 days
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Results: RECRUITING
BEST-RCT: Bevacizumab in Critically Severe COVID-19
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RCT parallel assigment
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Multicenter, China and Italy
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Groups:
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Arm 1: Bevacizumab 7.5 mg/kg IV
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Arm 2: Placebo
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1°: Time to clinical improvement (ordinal scale)
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Results: RECRUITING
BARI-COVID: Baricitinib in COVID-19 (Prato)
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JAK1/2 inhibitor
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Crossover trial, participants previously receiving an antiviral and/or HCQ
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Single center, Italy
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Groups:
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Arm 1: Before crossover
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Arm 2: Baricitinib 4 mg PO daily x 14 days
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1°: Percentage of patients requiring ICU
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Results: RECRUITING
Efficacy and Safety of Corticosteroids in COVID-19
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RCT
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Multisite, China
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Groups
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Arm 1: Methylprednisolone 1 mg/kg daily x 7 days
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Arm 2: Placebo
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1°: Time to clinical deterioration
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Results: RECRUITING
Ascorbic Acid in COVID-19 (Palermo)
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Single group intervnetional trial (n = 400)
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Single center, Italy
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Groups
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Arm: Ascorbic acid, 10 gm IV
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1°: In-hospital mortality
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Results: RECRUITING
HCQ4-COV19: Treatment of Cases and Chemoprophylaxis of Contacts
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Cluster RCT parallel assignment (n = 3040)
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Single site, Phase 3, Wuhan
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Groups
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Arm 1: Low risk - rhIFN-alpha nasal drops QID
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Arm 2: High risk - rhIFN-alpha nasal drops QID + thymosin alpha-1 SQ x 1
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1°: Incidence of COVID-19 acquisition
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Results: RECRUITING
COVID19-PEP: Post-exposure Therapy for SARS-COV-2
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RCT parallel assignment (n = 3040)
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Single site, Phase 3, Minnesota (USA)
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Groups
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Arm 1: HCQ 1400 mg day 1 + 600 mg days 2-5
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Arm 2: Placebo
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1°: Incidence of COVID-19 acquisition
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Results: RECRUITING
Recombinant IFN-alpha Nasal Drops for COVID-19 Prevention in HCWs
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Parallel assignment interventional trial
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Multisite, Phase 3, Spain
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Prezcobix (Darunavir 800/Cobicistat 150) + HCQ x 7 days vs Placebo
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1°: Incidence of secondary COVID-19 cases
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Results: RECRUITING
Safety and Immunity of COVID-19 a-APC Vaccine
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Single group interventional trial (n = 100)
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Multisite, Phase 1, China
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Groups
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Arm: Ex vivo transduction of antigen presenting cells (APCs) with SARS-COV-2 structural genes
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1°: Rate of positive T cell response
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Results: RECRUITING
Safety and Immunogenicity of COVID-19 mRNA Vaccine (NIH/NIAID)
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Liposome encapsulate mRNA coding for SARS-COV-2 spike (S) protein
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Single group interventional trial (n = 45)
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Multisite, Phase 1, US (Emory and UW)
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Groups
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Arm 1: mRNA-1273 25 mcg IM (day 1 and 29)
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Arm 2: mRNA-1273 100 mcg IM (day 1 and 29)
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Arm 3: mRNA-1273 250 mcg IM (day 1 and 29)
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1°: Geometric fold increase in IgG from baseline
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Results: RECRUITING