NVX2019nCOV501

A phase 2A/B, randomized, observer-blinded, placebocontrolled 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

Rationale

The purpose of this study is 2-fold: 1) to evaluate the efficacy, safety, and immunogenicity of SARS-CoV-2 rS with Matrix-M1 adjuvant in serologically naïve (to SARS-CoV-2) healthy human immunodeficiency virus (HIV)-negative adult subjects (Cohort 1 – HIV-negative) and 2) to evaluate the safety and immunogenicity of SARS-CoV-2 rS with Matrix-M1 adjuvant in serologically naïve (to SARS-CoV-2) medically stable HIV-positive adult subjects (Cohort 2 – HIV-positive). The study will be conducted at anticipated high COVID-19 transmission areas in South Africa expected to occur from July 2020 and onwards during the Southern Hemisphere winter and beyond. The information provided in this study will inform progression of development efforts to take the vaccine forward in an emergency use authorization setting and/or for Phase 3 efficacy or effectiveness study(ies).

Primary Objectives 1

To evaluate the efficacy of SARS-CoV-2 rS with Matrix-M1 adjuvant compared to placebo on the occurrence of symptomatic mild, moderate, or severe confirmed COVID-19 as demonstrated by qualitative polymerase chain reaction (PCR) in serologically naïve (to SARS-CoV-2) healthy HIV-negative adult subjects.

To evaluate the efficacy of SARS-CoV-2 rS with Matrix-M1 adjuvant compared to placebo on the occurrence of symptomatic moderate or severe confirmed COVID-19 as demonstrated by qualitative PCR in serologically naïve (to SARS-CoV-2) healthy HIV-negative adult subjects.

To accumulate and describe the safety experience for SARS-CoV-2 rS with Matrix-M1 adjuvant based on solicited short-term reactogenicity across a broad age spectrum (by toxicity grade) and by adverse event (AE) profile for vaccination through Day 35 in healthy HIV-negative adult subjects regardless of baseline serostatus and stratified by baseline serostatus.

Primary Objectives 2

To accumulate and describe the safety experience for SARS-CoV-2 rS with Matrix-M1 adjuvant based on solicited short-term reactogenicity across a broad age spectrum (by toxicity grade) and by AE profile for vaccination through Day 35 in medically stable HIV-positive adult subjects regardless of baseline serostatus and stratified by baseline serostatus.

To assess the immune response (IgG antibody to SARS-CoV-2 rS protein) for SARS-CoV-2 rS with Matrix-M1 adjuvant at Day 35 and whether baseline immune status (to SARS-CoV-2) has an impact in medically stable HIV-positive adult subjects (ie, regardless of baseline serostatus and stratified by baseline serostatus)

Study Design

This is a Phase 2a/b, randomized, observer-blinded, placebo-controlled study to evaluate the efficacy, safety, and immunogenicity of SARS-CoV-2 rS with Matrix-M1 adjuvant in healthy HIV-negative adult subjects (Cohort 1 – HIV-negative).

This study will also evaluate the safety and immunogenicity of SARS-CoV-2 rS with Matrix-M1 adjuvant in medically stable HIV-positive adult subjects (Cohort 2 – HIV-positive). The study will be conducted at anticipated high COVID-19 transmission areas in South Africa expected to occur from July 2020 and onwards during the Southern Hemisphere winter and beyond. After signing the informed consent form (ICF), subjects may be screened within a window of up to approximately 45 days. In addition, subjects must have a screening qualitative PCR for SARS-CoV-2 performed with a negative test result within 5 days prior to Day 0 vaccination in order to exclude subjects with active SARS-CoV-2 infection at the time of initial vaccination. Subjects will be asked to provide consent for the use of samples for future testing or assay development specific to SARS-CoV-2 (or related variants).

Blood samples for HIV testing of presumptive HIV-negative subjects will be collected at screening for inclusion for randomization. HIV-positive subjects will have CD4+ and HIV-1 viral load assessments to confirm that subjects do not have moderate or severe immunosuppression on treatment (see eligibility criteria); blood samples for other serology (hepatitis B and hepatitis C) will be collected at baseline but will not be used for inclusion/exclusion for randomization as a medical history will suffice; however, individuals with positive serologies (hepatitis B or hepatitis C) will not be included in the primary and secondary immunogenicity analyses.

Subjects testing negative or positive for COVID-19 antibodies at baseline will have immune responses assessed/reported separately, unless otherwise specified. All screening laboratory testing will be performed at one or more central contract laboratories using common testing methodology. Safety bloods will not be collected.

A minimum of approximately 3,200 to a maximum of approximately 4,404 male and female adult subjects aged ≥ 18 to < 85 years comprising a minimum of approximately 2,960 to a maximum of approximately 4,164 healthy HIV-negative adult subjects aged ≥ 18 to < 85 years (Cohort 1 – HIV-negative) and approximately 240 medically stable HIV-positive adult subjects aged ≥ 18 to < 65 years (Cohort 2 – HIV-positive) is planned for the study. For Cohort 1, an effort will be made to enrol a target of 10-25% of subjects who are ≥ 65 years of age. Within each cohort, subjects will be randomized in a 1:1 ratio via block randomization to receive up to 2 IM injections of study vaccine.

Cohort 1 (HIV-negative) will commence enrolment first, with vaccination starting following, and contingent on, determination of an adequate safety profile of SARS-CoV-2 rS with Matrix-M1 adjuvant through Day 35 (ie, 14 days post-second dose) in the ongoing Phase 1 portion of Protocol 2019nCoV-101 (Australia) by the global Safety Monitoring Committee (SMC) that is anticipated to be available by late July/early August 2020. Enrolment and vaccination in each cohort will be staged for the purpose of safety.

In Cohort 1 (HIV-negative), the first 888 subjects aged ≥ 18 to < 65 years (Stage 1) will be vaccinated and followed for at least 7 days after the first dose of study vaccine (Day 7). The global SMC will review unblinded safety/reactogenicity data through Day 7 to assess prespecified vaccination pause rules to allow commencement of vaccination in the remaining subjects aged ≥ 18 to < 85 years (Stage 2) of Cohort 1 (HIV-negative) and to commence concurrent vaccination of the first 80 subjects (Stage 1) of Cohort 2 (HIV-positive).

NOTE: subjects aged ≥ 65 to < 85 years will only be enrolled during Stage 2 of Cohort 1.

In Cohort 2 (HIV-positive), the first 80 subjects (Stage 1) will be vaccinated and followed for at least 7 days after the first dose of study vaccine (Day 7). The global SMC will review unblinded safety/reactogenicity data through Day 7 to allow prespecified vaccination pause rules to allow commencement of vaccination in the remaining 160 subjects (Stage 2) in Cohort 2 (HIV-positive)

Study Population

A minimum of approximately 3,200 to a maximum of approximately 4,404 subjects aged ≥ 18 to

< 85 years will be randomized in a blinded fashion at up to 15 sites across South Africa.

Investigators

Prof Lee Fairlie, Principal Investigator
Dr Gabrielle Benade,, co-Principal Investigator
Dr Faeezah Patel, Sub Investigator
Dr Masebole Masenya, Sub Investigator
Dr Elizea Horne, Sub-Investigator
Dr Alden Nicholas Geldenhuys, Sub Investigator
Dr Mrinmayee Dhar, Sub Investigator

Sponsors/Donors

Novavax Inc

Latest Update: 23 August 2021

For more about NVX2019nCOV501 please email rhicomms@wrhi.ac.za