Trial NCT04533399; PACTR202009726132275
Publication Madhi S, Lancet HIV, 2022
Dates: 2020-08-17 to 2020-11-25
Funding: Mixed (Novavax, Bill and Melinda Gates Foundation, Coalition for Epidemic Preparedness Innovations)
Conflict of interest: Yes

Methods
RCT
Location : Multicenter / South Africa
Follow-up duration (months): 1.63
• NVX-CoV2373 5 μg + Matrix-M1 (n=2213)
• Placebo (n=2206)
Inclusion criteriaHealthy human immunodeficiency virus (HIV)-negative adults 18 to 84 years of age ; medically stable people living with HIV (PLWH) 18 to 64 years of age.
Exclusion criteriaChronic administration of immunosuppressive therapy, autoimmune or immunodeficiency disease (except for medically stable PLWH); history of prior or current symptomatic Covid-19, or nucleic acid amplification test (NAAT)-confirmed SARS-CoV-2 infection within 5 days prior to anticipated initial dosing.
Interventions
Intervention
2 IM doses of 5 mcg NVX-CoV2373 with 50 mcg Matrix-M1 adjuvant, 21 days apart
Control
2 IM doses of saline placebo, 21 days apart
Participants
Randomized
4419 participants
Characteristics of participants
Type of participants: Healthy volunteers, Adults, People living with HIV
N=4419
2522 males
Children: 0
Pregnant women: 0
Immunocompromized patients: 246
Mean age:
Age range: NR
Description of participants
HIV-negative adults (18 to 84 years) and medically stable HIV-positive adults (18 to 64 years) at 16 sites in South Africa
Primary outcome
In the register
1) Cohort 1: HIV- Participants with Symptomatic Mild, Moderate, or Severe COVID-19 [ Time Frame: Day 28 to Day 386 ]; 2) Cohort 1: HIV- Participants with Symptomatic Moderate or Severe COVID-19 [ Time Frame: Day 28 to Day 386 ]; 3) Cohort 1: HIV- Participants with Solicited Adverse Events (AEs) [ Time Frame: 28 days ]; 4) Cohort 1: HIV- Participants with Unsolicited AEs [ Time Frame: 35 days ]; 5) Cohort 2: HIV+ Participants with Solicited AEs [ Time Frame: 28 days ]; 6) Cohort 2: HIV+ Participants with Unsolicited AEs [ Time Frame: 35 days ]; 7) Cohort 2: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as Geometric Mean Titers (GMTs) [ Time Frame: Day 35 ]; 8) Cohort 2: Serum IgG Antibody Levels Expressed as Geometric Mean Fold Rises (GMFRs) [ Time Frame: Day 35 ]; 9) Cohort 2: Serum IgG Antibody Levels Expressed as Seroconversion Rates (SCRs) [ Time Frame: Day 35 ]
In the report
To evaluate the reactogenicity and safety of NVX-CoV2373 during the 14 days after the second injection (day 35) in both HIV-negative individuals and people living with HIV-1;
Variants description
Variants
  • Beta
Description
Variant name: Beta
Direct evidence
Methods: Post hoc analysis
Missing outcome results: 3 cases (7%) with no sequence data (control arm)
Documents
avalaible

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing stated: Yes, Anonymised participant data will be made available when the trial is complete, upon request directed to the sponsor.
Data accessibility: Through a secure online platform after signing a data access agreement.
Risk of bias
Overall
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review		 Variant beta:

Some concerns
General comment Interim analysis. The follow-up is ongoing. In addition to the pre-print article, the study registry was used in data extraction and risk of bias assessment. The target sample size specified in the registry was achieved. There was no important change from the trial registration in the population, procedures, outcomes, or intervention and control interventions. The study reports preliminary efficacy and safety data for the Novovax vaccine in South Africa, where the B.1.351 Variant was the predominant SARS-COV-2 strain. Although multiple laboratory outcomes included in the registry were not reported, this was judged to be appropriate for a preliminary report. Safety data were only available for the participants from the earliest recruitment phase at the time of reporting.
This trial was updated on May 12th, 2021 after publication of the study report. This trial was updated on July 25th 2022, after the publication of a second study report.