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)

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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SARS-CoV-2 Infection

Intervention / Treatment
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* Biological: NVX-CoV2373


Participation Criteria
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Eligibility Criteria
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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. Vital signs must be within medically acceptable ranges prior to the first vaccination Agree to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study. For well-controlled PLWH 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. PLWH being managed on a stable/unchanged antiretroviral therapy (ART) regimen for at least 2 months prior to enrollment. No opportunistic infections in the past year. For less-well-controlled PLWH 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. PLWH being managed on a stable/unchanged (ART) regimen for at least 1 month prior to enrollment. 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-19. 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). Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of study. 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. 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). 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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 PLWH<br>Two doses of 5μg monovalent prototype vaccine+50µg Matrix-M adjuvant, given on Day 0 and Day 21. Alternating IM (deltoid) injection of placebo (0.5mL) given on Day 70. | Biological: NVX-CoV2373<br>* Alternating intramuscular (IM) (deltoid) injections of monovalent prototype vaccine premixed with Matrix-M™ adjuvant (0.5 mL) given either as 2 doses (one on Day 0 and one on Day 21 or Day 70) and an injection of placebo (0.5mL) on Day 21 or Day 70, or 3 doses (Day 0, Day 21, and Day 70).<br>* Other names: Monovalent SARS-CoV-2 rS vaccine premixed with Matrix-M adjuvant;|
| Experimental: Group 2 PLWH<br>Three doses of 5μg monovalent prototype vaccine+50µg Matrix-M adjuvant, given on Day 0, Day 21, and Day 70. | Biological: NVX-CoV2373<br>* Alternating intramuscular (IM) (deltoid) injections of monovalent prototype vaccine premixed with Matrix-M™ adjuvant (0.5 mL) given either as 2 doses (one on Day 0 and one on Day 21 or Day 70) and an injection of placebo (0.5mL) on Day 21 or Day 70, or 3 doses (Day 0, Day 21, and Day 70).<br>* Other names: Monovalent SARS-CoV-2 rS vaccine premixed with Matrix-M adjuvant;|
| Experimental: Group 3 PLWH<br>Two doses of 5μg monovalent prototype vaccine+50µg Matrix-M adjuvant, given on Day 0 and Day 70. Alternating IM (deltoid) injection of placebo (0.5mL) given on Day 21. | Biological: NVX-CoV2373<br>* Alternating intramuscular (IM) (deltoid) injections of monovalent prototype vaccine premixed with Matrix-M™ adjuvant (0.5 mL) given either as 2 doses (one on Day 0 and one on Day 21 or Day 70) and an injection of placebo (0.5mL) on Day 21 or Day 70, or 3 doses (Day 0, Day 21, and Day 70).<br>* Other names: Monovalent SARS-CoV-2 rS vaccine premixed with Matrix-M adjuvant;|
| Experimental: Group 4 HIV-Negative Participants<br>2 doses of 5μg monovalent prototype vaccine+50µg Matrix-M adjuvant, given on Day 0 and Day 21. Alternating IM (deltoid) injection of placebo (0.5mL) given on Day 70. | Biological: NVX-CoV2373<br>* Alternating intramuscular (IM) (deltoid) injections of monovalent prototype vaccine premixed with Matrix-M™ adjuvant (0.5 mL) given either as 2 doses (one on Day 0 and one on Day 21 or Day 70) and an injection of placebo (0.5mL) on Day 21 or Day 70, or 3 doses (Day 0, Day 21, and Day 70).<br>* Other names: Monovalent SARS-CoV-2 rS vaccine premixed with Matrix-M adjuvant;|
| Experimental: Group 5 HIV-Negative Participants<br>Two doses of 5μg monovalent prototype vaccine+50µg Matrix-M adjuvant, given on Day 0 and Day 70. Alternating IM (deltoid) injection of placebo (0.5mL) given on Day 21. | Biological: NVX-CoV2373<br>* Alternating intramuscular (IM) (deltoid) injections of monovalent prototype vaccine premixed with Matrix-M™ adjuvant (0.5 mL) given either as 2 doses (one on Day 0 and one on Day 21 or Day 70) and an injection of placebo (0.5mL) on Day 21 or Day 70, or 3 doses (Day 0, Day 21, and Day 70).<br>* Other names: Monovalent SARS-CoV-2 rS vaccine premixed with Matrix-M adjuvant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of PLWH with unsolicited adverse events (AEs) | Number of PLWH with unsolicited AEs stratified by level of control of HIV infection. | Day 84 | 
| Number of HIV-Negative participants with unsolicited AEs | Number of HIV-Negative participants with unsolicited AEs. | Day 84 | 
| Number of PLWH with unsolicited AEs | Number of PLWH with unsolicited AEs stratified by level of control of HIV infection. | Day 120 | 
| Number of PLWH with unsolicited AEs | Number of PLWH with unsolicited AEs stratified by level of control of HIV infection. | Day 180 | 
| Number of HIV-Negative participants with unsolicited AEs | Number of HIV-Negative participants with unsolicited AEs. | Day 120 | 
| Number of HIV-Negative participants with unsolicited AEs | Number of HIV-Negative participants with unsolicited AEs. | Day 180 | 
| Number of PLWH with solicited systemic AEs | 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. | Day 0 | 
| Number of PLWH with solicited systemic AEs | 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. | Day 21 | 
| Number of PLWH with solicited systemic AEs | 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. | Day 70 | 
| Number of HIV-Negative participants with solicited systemic AEs | Number of HIV-Negative participants with solicited systemic AEs for 7 days following each vaccination. | Day 0 | 
| Number of HIV-Negative participants with solicited systemic AEs | Number of HIV-Negative participants with solicited systemic AEs for 7 days following each vaccination. | Day 21 | 
| Number of HIV-Negative participants with solicited systemic AEs | Number of HIV-Negative participants with solicited systemic AEs for 7 days following each vaccination. | Day 70 | 
| Number of PLWH with solicited local AEs | 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. | Day 0 | 
| Number of PLWH with solicited local AEs | 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. | Day 21 | 
| Number of PLWH with solicited local AEs | 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. | Day 70 | 
| Number of HIV-Negative participants with solicited local AEs | Number of HIV-Negative participants with solicited local AEs for 7 days following each vaccination. | Day 0 | 
| Number of HIV-Negative participants with solicited local AEs | Number of HIV-Negative participants with solicited local AEs for 7 days following each vaccination. | Day 21 | 
| Number of HIV-Negative participants with solicited local AEs | Number of HIV-Negative participants with solicited local AEs for 7 days following each vaccination. | Day 70 | 
| Serum Immunoglobulin (IgG) antibody levels expressed as geometric mean enzyme-linked immunosorbent assay units (GMEU) | 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. | Day 21 | 
| Serum Immunoglobulin (IgG) antibody levels expressed as geometric mean enzyme-linked immunosorbent assay units (GMEU) | 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. | Day 35 | 
| Serum Immunoglobulin (IgG) antibody levels expressed as geometric mean enzyme-linked immunosorbent assay units (GMEU) | 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. | Day 70 | 
| Serum Immunoglobulin (IgG) antibody levels expressed as geometric mean enzyme-linked immunosorbent assay units (GMEU) | 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. | Day 84 | 
| Serum IgG antibody levels expressed as geometric mean fold rise (GMFR) | 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. | Day 21 | 
| Serum IgG antibody levels expressed as geometric mean fold rise (GMFR) | 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. | Day 35 | 
| Serum IgG antibody levels expressed as geometric mean fold rise (GMFR) | 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. | Day 70 | 
| Serum IgG antibody levels expressed as geometric mean fold rise (GMFR) | 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. | Day 84 | 
| Serum IgG antibody levels expressed as seroconversion rate (SCR) | 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. | Day 21 | 
| Serum IgG antibody levels expressed as seroconversion rate (SCR) | 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. | Day 35 | 
| Serum IgG antibody levels expressed as seroconversion rate (SCR) | 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. | Day 70 | 
| Serum IgG antibody levels expressed as seroconversion rate (SCR) | 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. | Day 84 | 
| Human angiotensin-converting enzyme 2 (hACE2) receptor binding inhibition assay expressed as geometric mean titer (GMT) | 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. | Day 21 | 
| Human angiotensin-converting enzyme 2 (hACE2) receptor binding inhibition assay expressed as geometric mean titer (GMT) | 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. | Day 35 | 
| Human angiotensin-converting enzyme 2 (hACE2) receptor binding inhibition assay expressed as geometric mean titer (GMT) | 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. | Day 70 | 
| Human angiotensin-converting enzyme 2 (hACE2) receptor binding inhibition assay expressed as geometric mean titer (GMT) | 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. | Day 84 | 
| hACE2 receptor binding inhibition assay expressed as GMFR | 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. | Day 21 | 
| hACE2 receptor binding inhibition assay expressed as GMFR | 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. | Day 35 | 
| hACE2 receptor binding inhibition assay expressed as GMFR | 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. | Day 70 | 
| hACE2 receptor binding inhibition assay expressed as GMFR | 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. | Day 84 | 
| hACE2 receptor binding inhibition assay expressed as SCR | 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. | Day 21 | 
| hACE2 receptor binding inhibition assay expressed as SCR | 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. | Day 35 | 
| hACE2 receptor binding inhibition assay expressed as SCR | 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. | Day 70 | 
| hACE2 receptor binding inhibition assay expressed as SCR | 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. | Day 84 | 
| Neutralizing antibody activity expressed as GMT | Titers of neutralizing antibody to the prototype virus expressed as GMT in PLWH stratified by level of control of HIV infection. | Day 35 | 
| Neutralizing antibody activity expressed as GMT | Titers of neutralizing antibody to the prototype virus expressed as GMT in PLWH stratified by level of control of HIV infection. | Day 84 | 
| Neutralizing antibody activity expressed as SCR | Titers of neutralizing antibody to the prototype virus expressed as SCR in PLWH stratified by level of control of HIV infection. | Day 35 | 
| Neutralizing antibody activity expressed as SCR | Titers of neutralizing antibody to the prototype virus expressed as SCR in PLWH stratified by level of control of HIV infection. | Day 84 | 
| Neutralizing antibody activity expressed as GMFR | Titers of neutralizing antibodies to the prototype virus expressed as GMFR in PLWH stratified by level of control of HIV infection. | Day 35 | 
| Neutralizing antibody activity expressed as GMFR | Titers of neutralizing antibodies to the prototype virus expressed as GMFR in PLWH stratified by level of control of HIV infection. | Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum IgG antibody levels expressed as GMEU | Serum IgG antibody levels assayed with the SARS-CoV-2 rS protein expressed as GMEUs in HIV-negative participants. | Day 21 | 
| Serum IgG antibody levels expressed as GMEU | Serum IgG antibody levels assayed with the SARS-CoV-2 rS protein expressed as GMEUs in HIV-negative participants. | Day 35 | 
| Serum IgG antibody levels expressed as GMEU | Serum IgG antibody levels assayed with the SARS-CoV-2 rS protein expressed as GMEUs in HIV-negative participants. | Day 70 | 
| Serum IgG antibody levels expressed as GMEU | Serum IgG antibody levels assayed with the SARS-CoV-2 rS protein expressed as GMEUs in HIV-negative participants. | Day 84 | 
| Serum IgG antibody levels expressed as GMFR | Serum IgG antibody levels assayed with the SARS-CoV-2 rS protein expressed as GMFR in HIV-negative participants. | Day 21 | 
| Serum IgG antibody levels expressed as GMFR | Serum IgG antibody levels assayed with the SARS-CoV-2 rS protein expressed as GMFR in HIV-negative participants. | Day 35 | 
| Serum IgG antibody levels expressed as GMFR | Serum IgG antibody levels assayed with the SARS-CoV-2 rS protein expressed as GMFR in HIV-negative participants. | Day 70 | 
| Serum IgG antibody levels expressed as GMFR | Serum IgG antibody levels assayed with the SARS-CoV-2 rS protein expressed as GMFR in HIV-negative participants. | Day 84 | 
| Serum IgG antibody levels expressed as SCR | Serum IgG antibody levels assayed with the SARS-CoV-2 rS protein expressed as SCR in HIV-negative participants. | Day 21 | 
| Serum IgG antibody levels expressed as SCR | Serum IgG antibody levels assayed with the SARS-CoV-2 rS protein expressed as SCR in HIV-negative participants. | Day 35 | 
| Serum IgG antibody levels expressed as SCR | Serum IgG antibody levels assayed with the SARS-CoV-2 rS protein expressed as SCR in HIV-negative participants. | Day 70 | 
| Serum IgG antibody levels expressed as SCR | Serum IgG antibody levels assayed with the SARS-CoV-2 rS protein expressed as SCR in HIV-negative participants. | Day 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronavirus disease 2019 (COVID-19), HIV