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)

SARS-CoV-2 Infection Clinical Trial

— COVID-19  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05112848
• Other study ID #: 2019nCoV-505
• Status: Completed
• Phase: Phase 2
• Start date: February 28, 2022
• Est. completion date: November 30, 2022

Study information

• Verified date: March 2023
• Source: Novavax
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 384
• Est. completion date: November 30, 2022
• Est. primary completion date: May 23, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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).

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV-2 Infection

Intervention

Biological:
• NVX-CoV2373
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).

Locations

Country	Name	City	State
South Africa	Josha Research	Bloemfontein	Free State
South Africa	Madibeng Centre for Research	Brits	North-West
South Africa	Wits Vaccines & Infectious Diseases Analytics (VIDA) Research Unit	Diepkloof	Johannesburg
South Africa	Wits RHI Shandukani Research Centre	Hillbrow	Johannesburg
South Africa	MERC Research (Pty) Ltd - Middelburg	Middelburg	Mpumalanga
South Africa	The Aurum Institute Pretoria Clinical Research Services	Pretoria	Gauteng
South Africa	KwaPhila Health Solutions (Enhancing Care)	Westridge	Durban

Sponsors (1)

Lead Sponsor	Collaborator
Novavax

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of PLWH with unsolicited adverse events (AEs)	Number of PLWH with unsolicited AEs stratified by level of control of HIV infection.	Day 84
Primary	Number of HIV-Negative participants with unsolicited AEs	Number of HIV-Negative participants with unsolicited AEs.	Day 84
Primary	Number of PLWH with unsolicited AEs	Number of PLWH with unsolicited AEs stratified by level of control of HIV infection.	Day 120
Primary	Number of PLWH with unsolicited AEs	Number of PLWH with unsolicited AEs stratified by level of control of HIV infection.	Day 180
Primary	Number of HIV-Negative participants with unsolicited AEs	Number of HIV-Negative participants with unsolicited AEs.	Day 120
Primary	Number of HIV-Negative participants with unsolicited AEs	Number of HIV-Negative participants with unsolicited AEs.	Day 180
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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