Clinical trial NCT04533399: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: SARS-CoV-2 Infection
COVID-19
Keywords: Coronavirus
Lead sponsor: Novavax
Sponsor class: INDUSTRY
Collaborators: name: Bill and Melinda Gates Foundation
First posted: 2020-08-31
Enrollment: 4422
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

All subjects:

* Adult male and female aged ≥ 18 to \< 65 years at screening for Cohorts 1 and 2 and Adult male or female aged ≥ 65 to \< 85 years at screening for Cohort 1 only.
* 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

Primary outcomes:
measure: Cohort 1: HIV- Participants with Symptomatic Mild, Moderate, or Severe COVID-19
timeFrame: Day 28 to Day 386
measure: Cohort 2: HIV + Participants with Symptomatic Mild, Moderate, or Severe COVID-19
timeFrame: Day 28 to Day 386
measure: Cohort 1: HIV- Participants with Solicited Adverse Events (AEs)
timeFrame: 28 days
measure: Cohort 1: HIV- Participants with Unsolicited AEs
timeFrame: 35 days
measure: Cohort 2: HIV+ Participants with Solicited AEs
timeFrame: 28 days
measure: Cohort 2: HIV+ Participants with Unsolicited AEs
timeFrame: 35 days
measure: Cohort 2: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as Geometric Mean Titers (GMTs)
timeFrame: Day 35
measure: Cohort 2: Serum IgG Antibody Levels Expressed as Geometric Mean Fold Rises (GMFRs)
timeFrame: Day 35
measure: Cohort 2: Serum IgG Antibody Levels Expressed as Seroconversion Rates (SCRs)
timeFrame: Day 35
measure: Healthcare Worker Expansion (Cohort 3): Participants with AESI's
timeFrame: Day 35
measure: Healthcare Worker Expansion (Cohort 4): Participants with AESI's
timeFrame: Day 70
Secondary outcomes:
measure: Cohort 1: HIV- Participants with Individual Strata of Symptomatic Virologically Confirmed, Mild, Moderate, or Severe COVID-19
timeFrame: Day 28 to Day 386
measure: Cohort 1: HIV- Participants with COVID-19 Requiring Hospitalization
timeFrame: Day 28 to Day 386
measure: Cohort 1: Incidence, Maximum Severity Score, and Symptom Duration of SARS-CoV-2 Infection by Severity Classification
timeFrame: Day 28 to Day 386
measure: Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMTs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMFRs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as SCRs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 1: Angiotensin-Converting Enzyme 2 (ACE2) Receptor Binding Inhibition Assay Expressed as GMTs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 1: ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 1: ACE2 Receptor Binding Inhibition Assay Expressed as SCRs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 1: ACE2 Receptor Binding Inhibition Assay Expressed as Seroresponse Rates (SRRs)
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 1: Neutralizing Antibody Activity Expressed as GMTs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 1: Neutralizing Antibody Activity Expressed as GMFRs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 1: Neutralizing Antibody Activity Expressed as SCRs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 1: Neutralizing Antibody Activity Expressed as SRRs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 1: HIV- Participants with Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), and Serious Adverse Events (SAEs)
timeFrame: 386 days
measure: Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMTs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMFRs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as SCRs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as GMTs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as SCRs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as SRRs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 2: Neutralizing Antibody Activity Expressed as GMTs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 2: Neutralizing Antibody Activity Expressed as GMFRs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 2: Neutralizing Antibody Activity Expressed as SCRs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 2: Neutralizing Antibody Activity Expressed as SRRs
timeFrame: Day 0 to 6 months after the last vaccination
measure: Cohort 2: HIV+ Participants with MAAEs, AESIs, and SAEs
timeFrame: 386 days
measure: Cohort 2: HIV+ Participants with Symptomatic Virologically Confirmed, Mild, Moderate, or Severe COVID-19
timeFrame: Day 28 to Day 385
measure: Cohort 2: Incidence, Maximum Severity Score, and Symptom Duration of SARS-CoV-2 Infection by Severity Classification
timeFrame: Day 28 to Day 385
measure: Cohort 1: HIV- Participants with Asymptomatic, Symptomatic Mild, Moderate, or Severe COVID-19
timeFrame: Day 28
measure: Cohort 2: HIV+ Participants with Asymptomatic, Symptomatic Mild, Moderate, or Severe COVID-19
timeFrame: Day 28
measure: Healthcare Worker Expansion (Cohort 3): Serum IgG Antibody Expressed as GMT
timeFrame: Day 35
measure: Healthcare Worker Expansion (Cohort 3): Serum IgG Antibody Expressed as GMEU
timeFrame: Day 35
measure: Healthcare Worker Expansion (Cohort 3): Serum IgG Antibody Expressed as GMFR
timeFrame: Day 35
measure: Healthcare Worker Expansion (Cohort 3): Serum IgG Antibody Expressed as SCR
timeFrame: Day 35
measure: Healthcare Worker Expansion (Cohort 4): Serum IgG Antibody Expressed as GMT
timeFrame: Day 70
measure: Healthcare Worker Expansion (Cohort 4): Serum IgG Antibody Expressed as GMEU
timeFrame: Day 70
measure: Healthcare Worker Expansion (Cohort 4): Serum IgG Antibody Expressed as GMFR
timeFrame: Day 70
measure: Healthcare Worker Expansion (Cohort 4): Serum IgG Antibody Expressed as SCR
timeFrame: Day 70
Other outcomes:
Locations:
city: Bloemfontein
country: South Africa
facility: ZA018
state: Free State Of South Africa
city: Hillbrow
country: South Africa
facility: ZA003
state: Gauteng
city: Johannesburg
country: South Africa
facility: Site ZA001
state: Gauteng
city: Johannesburg
country: South Africa
facility: ZA012
state: Gauteng
city: Pretoria
country: South Africa
facility: Site ZA015
state: Gauteng
city: Pretoria
country: South Africa
facility: ZA023
state: Gauteng
city: Durban
country: South Africa
facility: ZA019
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: ZA020
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: ZA021
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: ZA024
state: KwaZulu-Natal
city: Thabazimbi
country: South Africa
facility: ZA007
state: Limpopo
city: Madibeng
country: South Africa
facility: ZA022
state: North-West
city: Cape Town
country: South Africa
facility: ZA013
state: Western Cape
city: Worcester
country: South Africa
facility: ZA014
state: Western Cape
Study officials:
affiliation: Novavax, Inc.
name: Clinical Development
role: STUDY_DIRECTOR
References:
citation: Madhi SA, Moodley D, Hanley S, Archary M, Hoosain Z, Lalloo U, Louw C, Fairlie L, Fouche LF, Masilela MSL, Singh N, Grobbelaar C, Ahmed K, Benade G, Bhikha S, Bhorat AE, Bhorat Q, Joseph N, Dheda K, Esmail A, Foulkes S, Goga A, Oommen Jose A, Kruger G, Kalonji DJ, Lalloo N, Lombaard JJ, Lombard Koen A, Kany Luabeya A, Mngqibisa R, Petrick FG, Pitsi A, Tameris M, Thombrayil A, Vollgraaff PL, Cloney-Clark S, Zhu M, Bennett C, Albert G, Faust E, Plested JS, Fries L, Robertson A, Neal S, Cho I, Glenn GM, Shinde V; 2019nCoV-501 Study Group. Immunogenicity and safety of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine in people living with and without HIV-1 infection: a randomised, controlled, phase 2A/2B trial. Lancet HIV. 2022 May;9(5):e309-e322. doi: 10.1016/S2352-3018(22)00041-8.
citation: Shinde V, Bhikha S, Hoosain Z, Archary M, Bhorat Q, Fairlie L, Lalloo U, Masilela MSL, Moodley D, Hanley S, Fouche L, Louw C, Tameris M, Singh N, Goga A, Dheda K, Grobbelaar C, Kruger G, Carrim-Ganey N, Baillie V, de Oliveira T, Lombard Koen A, Lombaard JJ, Mngqibisa R, Bhorat AE, Benade G, Lalloo N, Pitsi A, Vollgraaff PL, Luabeya A, Esmail A, Petrick FG, Oommen-Jose A, Foulkes S, Ahmed K, Thombrayil A, Fries L, Cloney-Clark S, Zhu M, Bennett C, Albert G, Faust E, Plested JS, Robertson A, Neal S, Cho I, Glenn GM, Dubovsky F, Madhi SA; 2019nCoV-501 Study Group. Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med. 2021 May 20;384(20):1899-1909. doi: 10.1056/NEJMoa2103055. Epub 2021 May 5.