A Study Looking at the Effectiveness and Safety of a COVID-19 Vaccine in South African Adults

• ClinicalTrials.gov Identifier: NCT04533399
• Recruitment Status: Recruiting
• First Posted: August 31, 2020
• Last Update Posted: November 2, 2020
• Sponsor: Novavax
• Collaborator: Bill and Melinda Gates Foundation
• Information provided by (Responsible Party): Novavax

Tracking Information

• First Submitted Date: August 28, 2020
• First Posted Date: August 31, 2020
• Last Update Posted Date: November 2, 2020
• Actual Study Start Date: August 17, 2020
• Estimated Primary Completion Date: November 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 28, 2020)

• Cohort 1: HIV- Participants with Symptomatic Mild, Moderate, or Severe COVID-19 [ Time Frame: Day 28 to Day 386 ]
  Number of human immunodeficiency virus negative (HIV-) participants with first occurrence of positive (+) polymerase chain reaction (PCR), (+) PCR-confirmed, SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19 assessed from Day 28 (7 days after second vaccination dose) through the length of the study.
• Cohort 1: HIV- Participants with Symptomatic Moderate or Severe COVID-19 [ Time Frame: Day 28 to Day 386 ]
  Number of HIV- participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness with symptomatic moderate or severe COVID-19 assessed from Day 28 (7 days after second vaccination) through the length of the study.
• Cohort 1: HIV- Participants with Solicited Adverse Events (AEs) [ Time Frame: 28 days ]
  Numbers and percentages (with 95% confidence intervals [CIs]) of HIV- participants with solicited AEs, local and systemic, for 7 days following each vaccination (Days 0 and 21) by severity score, duration, and peak intensity.
• Cohort 1: HIV- Participants with Unsolicited AEs [ Time Frame: 35 days ]
  Numbers and percentages (with 95% CI) of HIV- participants with unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, MAAEs) through Day 35 by Medical Dictionary for Regulatory Activities (MedDRA) classification, severity score, and relatedness.
• Cohort 2: HIV+ Participants with Solicited AEs [ Time Frame: 28 days ]
  Numbers and percentages (with 95% CIs) of HIV+ participants with solicited AEs, local and systemic, for 7 days following each vaccination (Days 0 and 21) by severity score, duration, and peak intensity.
• Cohort 2: HIV+ Participants with Unsolicited AEs [ Time Frame: 35 days ]
  Numbers and percentages (with 95% CI) of HIV+ participants with unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, MAAEs) through Day 35 by MedDRA classification, severity score, and relatedness.
• Cohort 2: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as Geometric Mean Titers (GMTs) [ Time Frame: Day 35 ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by enzyme-linked immunosorbent assay (ELISA) expressed as GMTs at Day 35.
• Cohort 2: Serum IgG Antibody Levels Expressed as Geometric Mean Fold Rises (GMFRs) [ Time Frame: Day 35 ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Day 35.
• Cohort 2: Serum IgG Antibody Levels Expressed as Seroconversion Rates (SCRs) [ Time Frame: Day 35 ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCR at Day 35. SCR is defined as the percentage of participants with a post-vaccination titer ≥ 4 fold over naïve background and ≥ 2 fold over pre existing titer.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 19, 2020)

• Cohort 1: HIV- Participants with Individual Strata of Symptomatic Virologically Confirmed, Mild, Moderate, or Severe COVID-19 [ Time Frame: Day 28 to Day 386 ]
  Number of HIV- participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness in terms of individual strata of symptomatic virologically confirmed, mild, moderate, or severe COVID-19.
• Cohort 1: HIV- Participants with COVID-19 Requiring Hospitalization [ Time Frame: Day 28 to Day 386 ]
  Number of HIV- participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness with COVID-19 requiring hospitalization.
• Cohort 1: Incidence, Maximum Severity Score, and Symptom Duration of SARS-CoV-2 Infection by Severity Classification [ Time Frame: Day 28 to Day 386 ]
  Incidence, maximum severity score, and symptom duration of SARS-CoV-2 infection by classification of symptomatic virologically confirmed, mild, moderate, and/or severe disease in HIV- participants.
• Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMTs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV- participants.
• Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMFRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV- participants.
• Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as SCRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV- participants. SCR is defined as the percentage of participants with a post-vaccination titer ≥ 4 fold over naïve background and ≥ 2 fold over pre-existing titer.
• Cohort 1: Angiotensin-Converting Enzyme 2 (ACE2) Receptor Binding Inhibition Assay Expressed as GMTs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMTs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.
• Cohort 1: ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMFRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.
• Cohort 1: ACE2 Receptor Binding Inhibition Assay Expressed as SCRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SCRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.
• Cohort 1: ACE2 Receptor Binding Inhibition Assay Expressed as Seroresponse Rates (SRRs) [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SRRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants. SRR is defined as the proportion of participants with rises in titers exceeding the 95th percentile of placebo participants at the same time point and based on prior SARS-CoV-2 exposure.
• Cohort 1: Neutralizing Antibody Activity Expressed as GMTs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by microneutralization assay (MN) as expressed as GMTs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.
• Cohort 1: Neutralizing Antibody Activity Expressed as GMFRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by MN expressed as GMFRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV-participants.
• Cohort 1: Neutralizing Antibody Activity Expressed as SCRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by MN expressed as SCRs (≥ 4 fold change) at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.
• Cohort 1: Neutralizing Antibody Activity Expressed as SRRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by MN expressed as SRRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV-participants.
• Cohort 1: HIV- Participants with Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), and Serious Adverse Events (SAEs) [ Time Frame: 386 days ]
  Numbers and percentages (with 95% CI) of participants with MAAEs, AESI, or SAE through End of Study by MedDRA classification, severity score, and relatedness in HIV- participants.
• Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMTs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMFRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as SCRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV+ participants. SCR is defined as the percentage of participants with a post-vaccination titer ≥ 4 fold over naïve background and ≥ 2 fold over pre-existing titer.
• Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as GMTs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMTs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMFRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as SCRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SCRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as SRRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SRRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants. SRR is defined as the proportion of participants with rises in titers exceeding the 95th percentile of placebo participants at the same time point and based on prior SARS-CoV-2 exposure.
• Cohort 2: Neutralizing Antibody Activity Expressed as GMTs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by MN as expressed as GMTs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: Neutralizing Antibody Activity Expressed as GMFRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by MN expressed as GMFRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: Neutralizing Antibody Activity Expressed as SCRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by MN expressed as SCRs (≥ 4 fold change) at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: Neutralizing Antibody Activity Expressed as SRRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by MN expressed as SRRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: HIV+ Participants with MAAEs, AESIs, and SAEs [ Time Frame: 386 days ]
  Numbers and percentages (with 95% CI) of participants with MAAEs, AESI, or SAE through End of Study by MedDRA classification, severity score, and relatedness in HIV+ participants.
• Cohort 2: HIV+ Participants with Symptomatic Virologically Confirmed, Mild, Moderate, or Severe COVID-19 [ Time Frame: Day 28 to Day 385 ]
  Counts and proportions of symptomatic virologically confirmed, mild, moderate, and severe COVID-19 outcomes in HIV+ participants as previously described in the second primary efficacy endpoint for Cohort 1 (HIV- participants).
• Cohort 2: Incidence, Maximum Severity Score, and Symptom Duration of SARS-CoV-2 Infection by Severity Classification [ Time Frame: Day 28 to Day 385 ]
  Incidence, maximum severity score, and symptom duration of SARS-CoV-2 infection by classification of symptomatic virologically confirmed, mild, moderate, and/or severe disease in HIV+ participants.

Original Secondary Outcome Measures (submitted: August 28, 2020)

• Cohort 1: HIV- Participants with Individual Strata of Symptomatic Virologically Confirmed, Mild, Moderate, or Severe COVID-19 [ Time Frame: Day 28 to Day 386 ]
  Number of HIV- participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness in terms of individual strata of symptomatic virologically confirmed, mild, moderate, or severe COVID-19.
• Cohort 1: HIV- Participants with COVID-19 Requiring Hospitalization [ Time Frame: Day 28 to Day 386 ]
  Number of HIV- participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness with COVID-19 requiring hospitalization.
• Cohort 1: Incidence, Maximum Severity Score, and Symptom Duration of SARS-CoV-2 Infection by Severity Classification [ Time Frame: Day 28 to Day 386 ]
  Incidence, maximum severity score, and symptom duration of SARS-CoV-2 infection by classification of symptomatic virologically confirmed, mild, moderate, and/or severe disease in HIV- participants.
• Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMTs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV- participants.
• Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMFRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV- participants.
• Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as SCRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV- participants. SCR is defined as the percentage of participants with a post-vaccination titer ≥ 4 fold over naïve background and ≥ 2 fold over pre-existing titer.
• Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as Seroprotection Rates (SPRs) [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen as detected by ELISA expressed as SPRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV- participants. SPR is defined as the proportion of participants with rises in ELISA units exceeding the 95th percentile of placebo participants who remain COVID-19 free by symptom monitoring.
• Cohort 1: Angiotensin-Converting Enzyme 2 (ACE2) Receptor Binding Inhibition Assay Expressed as GMTs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMTs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.
• Cohort 1: ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMFRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.
• Cohort 1: ACE2 Receptor Binding Inhibition Assay Expressed as SCRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SCRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.
• Cohort 1: ACE2 Receptor Binding Inhibition Assay Expressed as Seroresponse Rates (SRRs) [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SRRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants. SRR is defined as the proportion of participants with rises in titers exceeding the 95th percentile of placebo participants at the same time point and based on prior SARS-CoV-2 exposure.
• Cohort 1: Neutralizing Antibody Activity Expressed as GMTs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by microneutralization assay (MN) as expressed as GMTs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.
• Cohort 1: Neutralizing Antibody Activity Expressed as GMFRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by MN expressed as GMFRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV-participants.
• Cohort 1: Neutralizing Antibody Activity Expressed as SCRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by MN expressed as SCRs (≥ 4 fold change) at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.
• Cohort 1: Neutralizing Antibody Activity Expressed as SRRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by MN expressed as SRRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV-participants.
• Cohort 1: HIV- Participants with Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), and Serious Adverse Events (SAEs) [ Time Frame: 386 days ]
  Numbers and percentages (with 95% CI) of participants with MAAEs, AESI, or SAE through End of Study by MedDRA classification, severity score, and relatedness in HIV- participants.
• Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMTs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMFRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as SCRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV+ participants. SCR is defined as the percentage of participants with a post-vaccination titer ≥ 4 fold over naïve background and ≥ 2 fold over pre-existing titer.
• Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as SPRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen as detected by ELISA expressed as SPRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV+ participants. SPR is defined as the proportion of participants with rises in ELISA units exceeding the 95th percentile of placebo participants who remain COVID-19 free by symptom monitoring.
• Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as GMTs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMTs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMFRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as SCRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SCRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as SRRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SRRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants. SRR is defined as the proportion of participants with rises in titers exceeding the 95th percentile of placebo participants at the same time point and based on prior SARS-CoV-2 exposure.
• Cohort 2: Neutralizing Antibody Activity Expressed as GMTs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by MN as expressed as GMTs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: Neutralizing Antibody Activity Expressed as GMFRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by MN expressed as GMFRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: Neutralizing Antibody Activity Expressed as SCRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by MN expressed as SCRs (≥ 4 fold change) at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: Neutralizing Antibody Activity Expressed as SRRs [ Time Frame: Day 0 to 6 months after the last vaccination ]
  Neutralizing antibody activity as detected by MN expressed as SRRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.
• Cohort 2: HIV+ Participants with MAAEs, AESIs, and SAEs [ Time Frame: 386 days ]
  Numbers and percentages (with 95% CI) of participants with MAAEs, AESI, or SAE through End of Study by MedDRA classification, severity score, and relatedness in HIV+ participants.
• Cohort 2: HIV+ Participants with Symptomatic Virologically Confirmed, Mild, Moderate, or Severe COVID-19 [ Time Frame: Day 28 to Day 385 ]
  Counts and proportions of symptomatic virologically confirmed, mild, moderate, and severe COVID-19 outcomes in HIV+ participants as previously described in the second primary efficacy endpoint for Cohort 1 (HIV- participants).
• Cohort 2: Incidence, Maximum Severity Score, and Symptom Duration of SARS-CoV-2 Infection by Severity Classification [ Time Frame: Day 28 to Day 385 ]
  Incidence, maximum severity score, and symptom duration of SARS-CoV-2 infection by classification of symptomatic virologically confirmed, mild, moderate, and/or severe disease in HIV+ participants.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Looking at the Effectiveness and Safety of a COVID-19 Vaccine in South African Adults
• Official Title: A Phase 2A/B, Randomized, Observer-blinded, Placebo-controlled Study to Evaluate the Efficacy, Immunogenicity, and Safety of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M1™ Adjuvant in South African Adult Subjects Living Without HIV; and Safety and Immunogenicity in Adults Living With HIV
• Brief Summary: This is a study to evaluate the effectiveness and safety of a coronavirus disease 2019 (COVID-19) vaccine called SARS-CoV-2 rS with Matrix-M1 adjuvant in a minimum of approximately 2,960 to a maximum of approximately 4,164 healthy HIV-negative (HIV-) adult participants and in approximately 240 medically stable HIV-positive (HIV+) adult participants in up to 15 sites across South Africa. A vaccine causes the body to have an immune response that may help prevent the infection or reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the protective effect, body's immune response, and safety of SARS-CoV-2 rS with Matrix-M1 adjuvant in these study populations. Participants in the study will randomly be assigned to receive SARS-CoV-2 rS with Matrix-M1 adjuvant or placebo. Each participant in the study will receive a total of 2 intramuscular injections over the course of the study.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention

Condition

• SARS-CoV-2 Infection
• COVID-19

Intervention

• Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant
  Alternating intramuscular (deltoid) injections of SARS-CoV-2 rS co-formulated with Matrix-M1 adjuvant (0.5 mL) on Days 0 and 21.
  Other Name: NVX-CoV2373
• Other: Placebo
  Alternating intramuscular (deltoid) injections of placebo (0.5 mL) on Days 0 and 21.
  Other Name: Sodium chloride 0.9% (BP, sterile)

Study Arms

• Experimental: Cohort 1 (HIV negative) 5 μg SARS-CoV-2 rS/Matrix-M1 Adjuvant
  2 doses of SARS-CoV-2 rS - 5 μg + 50 μg Matrix-M1 adjuvant (co-formulated), 1 dose each on Days 0 and 21.
  Intervention: Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant
• Placebo Comparator: Cohort 1 (HIV negative) Placebo
  2 doses of Placebo (Saline), 1 dose each on Days 0 and 21.
  Intervention: Other: Placebo
• Experimental: Cohort 2 (HIV positive) 5 μg SARS-CoV-2 rS/Matrix-M1 Adjuvant
  2 doses of SARS-CoV-2 rS - 5 μg + 50 μg Matrix-M1 adjuvant (co-formulated), 1 dose each on Days 0 and 21.
  Intervention: Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant
• Placebo Comparator: Cohort 2 (HIV positive) Placebo
  2 doses of Placebo (Saline), 1 dose each on Days 0 and 21.
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 19, 2020): 4400
• Original Estimated Enrollment (submitted: August 28, 2020): 2904
• Estimated Study Completion Date: November 2021
• Estimated Primary Completion Date: November 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

All subjects:

• 18 to 64 years at screening for Cohort 2 and 18 to 84 years at screening for Cohort 1.
• Body mass index (BMI) of 17 to 40 kg/m².
• Provides informed consent prior to study participation and is willing to comply with study procedures, including potential home visits.
• Women of child-bearing potential must agree not to have sexual intercourse with men, or must consistently use an agreed method of contraception from at least 21 days prior to enrolment in the study, through 6 months after the last vaccination.

HIV-negative subjects only:

• Documentation of HIV-negative test result by a method approved in South Africa.
• Healthy at study screening, as determined by the investigator.

HIV-positive subjects only:

• Documentation of HIV-positive test result by a method approved in South Africa.
• Receiving highly active antiretroviral therapy (HAART) and has been using the same regimen for at least 8 weeks before screening. Changes in antiretroviral dosage within 8 weeks of entering the study are allowed, as are exchanges in pharmacological formulations.
• Medically stable at screening, as determined by the investigator, and free of opportunistic infections in the 1 year prior to first study vaccination.
• Have a HIV-1 viral load < 1000 copies/mL within 45 days of randomization in the study.

Exclusion Criteria:

• Any current acute illness requiring medical or surgical care, or chronic illness (excluding HIV in HIV-positive subjects) that requires changes in medication in the past 2 months indicating that chronic illness/disease is not stable.

• Chronic disease, including:

  1. Hypertension (elevated blood pressure [BP]) ≥ grade 2 (systolic BP ≥ 160 mmHg; and/or diastolic BP ≥ 100 mmHg) according to the South African Hypertension Society's Practice Guidelines. NOTE: Hypertension [elevated BP] ≤ grade 1 (systolic BP ≤ 159 mmHg; diastolic BP ≤ 99 mmHg) according to the South African Hypertension Society's Practice Guidelines is NOT exclusionary;
  2. Congestive heart failure with a history of an acute exacerbation of any severity in the prior 2 years;
  3. Chronic obstructive pulmonary disease (COPD) with a history of an acute exacerbation of any severity in the past 2 years;
  4. Evidence of unstable coronary artery disease in the past 3 months, as determined by the investigator; NOTE: Stable coronary heart disease is NOT exclusionary.
  5. Asthma requiring regular/chronic control medication (eg, short-acting beta2-agonist [SABA] > 2 days per week; or any chronic use of inhaled corticosteroids [ICS], long-acting beta2-agonist [LABA], leukotriene receptor antagonist [LTRA], or oral corticosteroids), and/or worsening of asthma symptoms in the past 3 months; NOTE: Asthma not requiring regular/chronic control medication, and not requiring SABA > 2 days per week, and not demonstrating worsening of symptoms in the past 3 months, will NOT be excluded.
  6. Type 1 or 2 diabetes (adult onset) requiring treatment with insulin; NOTE: Non-insulin dependent type 2 diabetes is NOT exclusionary.
  7. Chronic kidney disease/renal insufficiency;
  8. Chronic gastrointestinal and hepatic diseases;
  9. Chronic neurological diseases (such as multiple sclerosis, dementia, transient ischemic attacks, Parkinson's disease, degenerative neurological conditions, neuropathy, or epilepsy), or a history of stroke within 12 months with residual symptoms, or previous neurological disorder within 12 months with residual symptoms; NOTE: History of migraine or chronic headaches, or nerve root compression that have been stable on treatment for the last 4 weeks are NOT exclusionary.
• Participation in research involving an investigational product (drug/biologic/device) within 45 days prior to first study vaccination.
• Prior receipt of investigational or approved COVID-19 vaccine at any time.
• History of a diagnosis of suspected or confirmed COVID-19.
• Received influenza (flu) vaccination within 14 days prior to first study vaccination; or any other vaccine within 4 weeks prior to first study vaccination; or planned vaccination with 5 weeks after first study vaccination.
• Any autoimmune or immunodeficiency disease/condition (excluding HIV in HIV-positive patients).
• Chronic (more than 14 days continuous) administration of immunosuppressant, systemic glucocorticosteroids, or other immune-modifying drugs within 90 days prior to first study vaccination (excluding HAART in HIV-positive subjects). NOTE: An immunosuppressant dose of glucocorticoid is defined as a systemic dose ≥ 10 mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted.
• Received immunoglobulin, blood-derived products, or other immunosuppressant drugs within 90 days prior to first study vaccination (excluding HAART in HIV-positive subjects).
• Acute respiratory and/or non-respiratory illness consistent with potential COVID-19, concurrent with or within 14 days prior to first study vaccination, or documented temperature of > 38°C during this period.
• Known blood clotting disorder.
• Active cancer (malignancy) within 3 years prior to first study vaccination (with the exception of adequately treated non-melanoma skin cancers, as assessed by the investigator).
• Any known allergies to products contained in the investigational product, or latex allergy, or any history of anaphylaxis in relation to any previous vaccination.
• Women who are breastfeeding or who are pregnant at the time of screening, or plan to become pregnant within the first 6 months of the study.
• History of alcohol abuse or drug addiction within 2 years prior to the first study vaccination.
• Any condition (other than HIV in HIV-positive subjects) that, in the opinion of the investigator, would pose a health risk to the subject if they participate in the study, or could interfere with evaluation of the study vaccine or interpretation of study results.
• Study team member or first-degree relative of any study member.

Other protocol-defined inclusion/exclusion criteria may apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 84 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Rani Naidoo; +27 (011) 6566167; premadevi.naidoo@ppdi.com

• Listed Location Countries: South Africa

Administrative Information

• NCT Number: NCT04533399
• Other Study ID Numbers: 2019nCoV-501
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Novavax
• Study Sponsor: Novavax
• Collaborators: Bill and Melinda Gates Foundation

Investigators

• Study Director: Vivek Shinde, MD, MPH; Novavax, Inc.
• Principal Investigator: Shabir A Madhi, MBBCH, PhD; University of Witwatersrand, South Africa

• PRS Account: Novavax
• Verification Date: October 2020