A Study to Evaluate Safety and Immunogenicity of a COVID-19 Vaccine in People Living With HIV at Risk for SARS-CoV-2 (COVID-19)

A Phase 2, Randomized, Observer-Blinded Study to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M™ Adjuvant in People Living With HIV

This is a Phase 2, randomized, observer-blinded study evaluating the safety and immunogenicity of SARS-CoV-2 with Matrix-M™ Adjuvant in people living with human immunodeficiency virus (HIV) (PLWH) and HIV- negative adults, seronegative to SARS-CoV-2 at baseline.

The investigational product will be a monovalent Serum Institute of India (SII) SARS CoV-2 vaccine at a dose of 5 µg antigen adjuvanted with 50 µg Matrix-M (referred hereafter as NVX-CoV2373).

Approximately 270 PLWH, 18 to 65 years of age inclusive, will be enrolled into 3 groups and stratified at presentation based on the level of control of HIV infection. All PLWH will be baseline seronegative (for SARS-CoV-2) and have not received any authorized SARS-CoV-2 vaccines. PLWH will be randomly assigned 1:1:1 to receive NVX-CoV2373 in either a two dose regimen on Days 0 and 21 or Days 0 and 70 or a three-dose regimen on Days 0, 21, and 70. Randomization of PLWH will be stratified by level of control of HIV infection to distribute well controlled and less well controlled participants approximately evenly among the 3 PLWH treatment groups. Approximately 90 HIV negative participants, 18 to 65 years of age inclusive, will be randomly assigned 1:1 to receive NVX-CoV2373 in a two dose regimen on Days 0 and 21 or Days 0 and 70. All HIV negative participants will be baseline seronegative (for SARS-CoV-2) and have not received any authorized SARS-CoV-2 vaccines. Placebo (normal saline solution) will be administered to participants who receive a two-dose regimen of NVX-CoV2373 to maintain overall blinding.

Inclusion Criteria:

1. Adults 18 to 65 years of age, inclusive, at screening.

2. Willing and able to give informed consent prior to study enrollment and to comply with study procedures.

3. Participants of childbearing potential (defined as any participant who has experienced menarche and who is NOT surgically sterile [ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea at least 12 consecutive months]) must agree to be heterosexually inactive from at least 28 days prior to enrollment and through the end of the study OR agree to consistently use a medically acceptable method of contraception listed below from at least 28 days prior to enrollment and through the end of the study.

   1. Condoms (male or female) with spermicide (if acceptable in-country)
   2. Diaphragm with spermicide
   3. Cervical cap with spermicide
   4. Intrauterine device
   5. Oral or patch contraceptives
   6. Norplant®, Depo-Provera®, or other in-country regulatory approved contraceptive method that is designed to protect against pregnancy.
   7. Abstinence as a form of contraception is acceptable if in line with the participant's lifestyle.

4. Vital signs must be within medically acceptable ranges prior to the first vaccination

5. Agree to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study.

   For well-controlled PLWH

6. PLWH with a cluster of differentiation 4 (CD4) + T-cell count of ≥ 350 cells/μL at screening or viral load of ≤ 1,000 copies/mL.

7. PLWH being managed on a stable/unchanged antiretroviral therapy (ART) regimen for at least 2 months prior to enrollment.

8. No opportunistic infections in the past year.

   For less-well-controlled PLWH

9. PLWH with a CD4+ T-cell count of ≥ 200 and < 350 cells/μL at screening or viral load of 1,000 to 10,000 copies/mL.

10. PLWH being managed on a stable/unchanged (ART) regimen for at least 1 month prior to enrollment.

Exclusion Criteria:

1. Laboratory-confirmed SARS-CoV-2 infection (PCR+ within 5 days prior to first study vaccination with results available before randomization) or positive anti-S protein antibody to SARS-CoV-2 at screening.
2. Previous receipt of any investigational or authorized/approved vaccine, prophylactic or therapeutic agent for the prevention or treatment of COVID-19.
3. Participation in research involving receipt of an investigational product (drug/biologic/device) within 90 days prior to the first study vaccination.
4. Received influenza vaccination within 14 days prior to first study vaccination, or any other vaccine within 30 days prior to first study vaccination.
5. Any known allergies to products contained in the investigational product.
6. Any history of anaphylaxis to any prior vaccine.
7. Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy.
8. Chronic administration (defined as > 14 continuous days) of immunosuppressant, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to first study vaccination.
9. Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to first study vaccination.
10. Active cancer (malignancy) on therapy within 3 years prior to first study vaccination (with the exception of adequately treated non-melanomatous skin carcinoma or lentigo maligna and uterine cervical carcinoma in situ without evidence of disease, at the discretion of the investigator).
11. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of study.
12. Suspected or known history of alcohol abuse or drug addiction within 2 years prior to the first study vaccine dose that, in the opinion of the investigator, might interfere with protocol compliance.
13. Any other condition that, in the opinion of the investigator, would pose a health risk to the participant if enrolled or could interfere with evaluation of the trial vaccine or interpretation of study results (including neurologic or psychiatric conditions likely to impair the quality of safety reporting).
14. Study team member or immediate family member of any study team member (inclusive of Sponsor, Contract Research Organization, and study site personnel involved in the conduct or planning of the study).