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

NCT04533399 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 2019nCoV-501
• Study Type: interventional
• Target: 4,422
• Locations: 1 country
• Sites: 14

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.

Conditions

SARS-CoV-2 Infection; COVID-19

Keywords

Coronavirus

Outcome Measures

Primary Outcomes (11)

• Cohort 1: HIV- Participants with Symptomatic Mild, Moderate, or Severe COVID-19

  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.

  Day 28 to Day 386

• Cohort 2: HIV + Participants with Symptomatic Mild, Moderate, or Severe COVID-19

  Number of HIV+ participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness with symptomatic mild,moderate or severe COVID-19 assessed from Day 28 (7 days after second vaccination) through the length of the study.

  Day 28 to Day 386

• Cohort 1: HIV- Participants with Solicited Adverse Events (AEs)

  Number 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.

  28 days

• Cohort 1: HIV- Participants with Unsolicited AEs

  Number 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.

  35 days

• Cohort 2: HIV+ Participants with Solicited AEs

  Number 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.

  28 days

• Cohort 2: HIV+ Participants with Unsolicited AEs

  Number 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.

  35 days

• Cohort 2: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as Geometric Mean Titers (GMTs)

  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.

  Day 35

• Cohort 2: Serum IgG Antibody Levels Expressed as Geometric Mean Fold Rises (GMFRs)

  Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Day 35.

  Day 35

• Cohort 2: Serum IgG Antibody Levels Expressed as Seroconversion Rates (SCRs)

  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.

  Day 35

• Healthcare Worker Expansion (Cohort 3): Participants with AESI's

  Number of healthy adult HCW, with AESIs for 14 days post second vaccination (Day 35) by severity score, duration, and peak intensity.

  Day 35

• Healthcare Worker Expansion (Cohort 4): Participants with AESI's

  Number of healthy adult HCW, with AESIs for 14 days post second vaccination (Day 70) by severity score, duration, and peak intensity.

  Day 70

Secondary Outcomes (39)

• Cohort 1: HIV- Participants with Individual Strata of Symptomatic Virologically Confirmed, Mild, Moderate, or Severe COVID-19

  Day 28 to Day 386

• Cohort 1: HIV- Participants with COVID-19 Requiring Hospitalization

  Day 28 to Day 386

• Cohort 1: Incidence, Maximum Severity Score, and Symptom Duration of SARS-CoV-2 Infection by Severity Classification

  Day 28 to Day 386

• Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMTs

  Day 0 to 6 months after the last vaccination

• Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMFRs

  Day 0 to 6 months after the last vaccination

Study Arms (4)

Cohort 1 (HIV negative) 5 μg SARS-CoV-2 rS/Matrix-M1 Adjuvant

EXPERIMENTAL

2 doses of SARS-CoV-2 rS - 5 μg + 50 μg Matrix-M1 adjuvant (co-formulated), 1 dose each on Days 0 and 21.

Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant

Cohort 1 (HIV negative) Placebo

PLACEBO COMPARATOR

2 doses of Placebo (Saline), 1 dose each on Days 0 and 21.

Other: Placebo

Cohort 2 (HIV positive) 5 μg SARS-CoV-2 rS/Matrix-M1 Adjuvant

EXPERIMENTAL

2 doses of SARS-CoV-2 rS - 5 μg + 50 μg Matrix-M1 adjuvant (co-formulated), 1 dose each on Days 0 and 21.

Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant

Cohort 2 (HIV positive) Placebo

PLACEBO COMPARATOR

2 doses of Placebo (Saline), 1 dose each on Days 0 and 21.

Other: Placebo

Interventions

SARS-CoV-2 rS/Matrix-M1 Adjuvant BIOLOGICAL

Alternating intramuscular (deltoid) injections of SARS-CoV-2 rS co-formulated with Matrix-M1 adjuvant (0.5 mL) on Days 0 and 21.

Also known as: NVX-CoV2373

Cohort 1 (HIV negative) 5 μg SARS-CoV-2 rS/Matrix-M1 Adjuvant; Cohort 2 (HIV positive) 5 μg SARS-CoV-2 rS/Matrix-M1 Adjuvant

Placebo OTHER

Alternating intramuscular (deltoid) injections of placebo (0.5 mL) on Days 0 and 21.

Also known as: Sodium chloride 0.9% (BP, sterile)

Cohort 1 (HIV negative) Placebo; Cohort 2 (HIV positive) Placebo

Eligibility Criteria

• Age: 18 Years - 84 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Congestive heart failure with a history of an acute exacerbation of any severity in the prior 2 years;
• Chronic obstructive pulmonary disease (COPD) with a history of an acute exacerbation of any severity in the past 2 years;
• 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.
• Chronic kidney disease/renal insufficiency;
• Chronic gastrointestinal and hepatic diseases;
• 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.

Sponsors & Collaborators

• Novavax: lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (14)

ZA018

Bloemfontein, Free State of South Africa, South Africa

Location

ZA003

Hillbrow, Gauteng, South Africa

Location

Site ZA001

Johannesburg, Gauteng, South Africa

Location

ZA012

Johannesburg, Gauteng, South Africa

Location

Site ZA015

Pretoria, Gauteng, South Africa

Location

ZA023

Pretoria, Gauteng, South Africa

Location

ZA019

Durban, KwaZulu-Natal, South Africa

Location

ZA020

Durban, KwaZulu-Natal, South Africa

Location

ZA021

Durban, KwaZulu-Natal, South Africa

Location

ZA024

Durban, KwaZulu-Natal, South Africa

Location

ZA007

Thabazimbi, Limpopo, South Africa

Location

ZA022

Madibeng, North West, South Africa

Location

ZA013

Cape Town, Western Cape, South Africa

Location

ZA014

Worcester, Western Cape, South Africa

Location

Related Publications (2)

• 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.

  PMID: 35489376 DERIVED

• 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.

  PMID: 33951374 DERIVED

Related Links

• FDA Safety Alerts and Recalls
• CDC (Centers for Disease Control and Prevention): Coronavirus (COVID-19) website
• WHO COVID-19 treatment guidelines
• WHO South Africa website
• COVID-19 Corona Virus - Department of Health, Republic of South Africa

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

NVX-CoV2373 adjuvated lipid nanoparticle; Sodium Chloride

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Clinical Development

  Novavax, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2020
• First Posted: August 31, 2020
• Study Start: August 17, 2020
• Primary Completion: December 7, 2021
• Study Completion: January 19, 2022
• Last Updated: February 17, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (14)