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
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- SARS-CoV-2 Infection
- Sponsor
- Novavax
- Enrollment
- 384
- Locations
- 7
- Primary Endpoint
- Number of PLWH with solicited local AEs
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adults 18 to 65 years of age, inclusive, at screening.
- •Willing and able to give informed consent prior to study enrollment and to comply with study procedures.
- •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.
- •Condoms (male or female) with spermicide (if acceptable in-country)
- •Diaphragm with spermicide
- •Cervical cap with spermicide
- •Intrauterine device
- •Oral or patch contraceptives
- •Norplant®, Depo-Provera®, or other in-country regulatory approved contraceptive method that is designed to protect against pregnancy.
- •Abstinence as a form of contraception is acceptable if in line with the participant's lifestyle.
Exclusion Criteria
- •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.
- •Previous receipt of any investigational or authorized/approved vaccine, prophylactic or therapeutic agent for the prevention or treatment of COVID-
- •Participation in research involving receipt of an investigational product (drug/biologic/device) within 90 days prior to the first study vaccination.
- •Received influenza vaccination within 14 days prior to first study vaccination, or any other vaccine within 30 days prior to first study vaccination.
- •Any known allergies to products contained in the investigational product.
- •Any history of anaphylaxis to any prior vaccine.
- •Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy.
- •Chronic administration (defined as \> 14 continuous days) of immunosuppressant, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to first study vaccination.
- •Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to first study vaccination.
- •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).
Outcomes
Primary Outcomes
Number of PLWH with solicited local AEs
Time Frame: Day 70
Number of PLWH with solicited local AEs for 7 days following each vaccination stratified by baseline severity of disease as determined by the level of control of HIV infection into well-controlled and less-well-controlled treatment groups.
Number of HIV-Negative participants with unsolicited AEs
Time Frame: Day 180
Number of HIV-Negative participants with unsolicited AEs.
Number of PLWH with unsolicited AEs
Time Frame: Day 180
Number of PLWH with unsolicited AEs stratified by level of control of HIV infection.
Serum Immunoglobulin (IgG) antibody levels expressed as geometric mean enzyme-linked immunosorbent assay units (GMEU)
Time Frame: Day 84
Serum IgG antibody levels assayed with the SARS-CoV-2 rS protein antigen expressed as GMEUs in PLWH stratified by level of control of HIV infection.
Serum IgG antibody levels expressed as geometric mean fold rise (GMFR)
Time Frame: Day 84
Serum IgG antibody levels assayed with the SARS-CoV-2 rS protein antigen expressed as GMFRs in PLWH stratified by level of control of HIV infection.
Neutralizing antibody activity expressed as SCR
Time Frame: Day 84
Titers of neutralizing antibody to the prototype virus expressed as SCR in PLWH stratified by level of control of HIV infection.
Neutralizing antibody activity expressed as GMFR
Time Frame: Day 84
Titers of neutralizing antibodies to the prototype virus expressed as GMFR in PLWH stratified by level of control of HIV infection.
Human angiotensin-converting enzyme 2 (hACE2) receptor binding inhibition assay expressed as geometric mean titer (GMT)
Time Frame: Day 84
Epitope-specific immune responses assayed with the SARS-CoV-2 rS protein receptor-binding domain measured by serum titers in an hACE2 receptor binding inhibition assay expressed as GMT in PLWH stratified by level of control of HIV infection.
hACE2 receptor binding inhibition assay expressed as SCR
Time Frame: Day 84
Epitope-specific immune responses assayed with the SARS-CoV-2 rS protein receptor-binding domain measured by serum titers in an hACE2 receptor binding inhibition assay expressed as SCR in PLWH stratified by level of control of HIV infection.
Number of PLWH with unsolicited adverse events (AEs)
Time Frame: Day 84
Number of PLWH with unsolicited AEs stratified by level of control of HIV infection.
Number of PLWH with solicited systemic AEs
Time Frame: Day 70
Number of PLWH with solicited systemic AEs for 7 days following each vaccination stratified by baseline severity of disease as determined by the level of control of HIV infection into well-controlled and less-well-controlled treatment groups.
Number of HIV-Negative participants with solicited systemic AEs
Time Frame: Day 70
Number of HIV-Negative participants with solicited systemic AEs for 7 days following each vaccination.
Serum IgG antibody levels expressed as seroconversion rate (SCR)
Time Frame: Day 84
Serum IgG antibody levels assayed with the SARS-CoV-2 rS protein antigen expressed as SCRs in PLWH stratified by level of control of HIV infection.
Number of HIV-Negative participants with solicited local AEs
Time Frame: Day 70
Number of HIV-Negative participants with solicited local AEs for 7 days following each vaccination.
Neutralizing antibody activity expressed as GMT
Time Frame: Day 84
Titers of neutralizing antibody to the prototype virus expressed as GMT in PLWH stratified by level of control of HIV infection.
hACE2 receptor binding inhibition assay expressed as GMFR
Time Frame: Day 84
Epitope-specific immune responses assayed with the SARS-CoV-2 rS protein receptor-binding domain measured by serum titers in an hACE2 receptor binding inhibition assay expressed as GMFR in PLWH stratified by level of control of HIV infection.
Secondary Outcomes
- Serum IgG antibody levels expressed as SCR(Day 84)
- Serum IgG antibody levels expressed as GMFR(Day 84)
- Serum IgG antibody levels expressed as GMEU(Day 84)