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Phase 2a Trial to Evaluate Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected/Uninfected Adults. (AUR1-8-341)

Primary Purpose

COVID-19

Status

Recruiting

Phase

Phase 2

Locations

South Africa

Study Type

Interventional

Intervention

Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine, SARS-CoV-2 rS (CovovaxTM), BNT162b2 (Pfizer)

About this trial

This is an interventional prevention trial for COVID-19 focused on measuring Vaccines

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

. Adult male or female aged 18 and above at the time of written informed consent
. Willing and able to give written informed consent
. HIV-infected persons on ART for at least three months prior to enrollment, or HIV-uninfected persons
. Able to provide evidence of completing a primary COVID-19 vaccination regimen with either a single dose of Ad26.COV2.S or two doses of BNT162b2 at least two months prior to enrolment, or HIV-infected with no prior COVID-19 vaccination and evidence of prior SAR-CoV-2 infection
. Residing in the vicinity of the clinical trial site and planning to remain in the area of the study for 12months
. Able and willing to participate for the duration of the study visits and follow-up
. Willing to provide verifiable identification (eg. Identity document, passport) at study entry and follow-up visits

Exclusion Criteria:

. Positive SARS-CoV-2 PCRor antigen detection test
. Persons with undocumented HIV status
. HIV-infected persons with CD4count <1 00 cells/mm3and/or Viral Load > 1000 copies/ml
. Known allergy or history of anaphylaxis or other serious adverse reactions to specific COVID-19 vaccine constituents
. History of capillary leak syndrome, thrombosis with thrombocytopenia syndrome (TTS), heparin-induced thrombocytopenia (HIT), history of any neurological disorders or seizures including Guillain-Barré syndrome, with the exception of febrile seizures during childhood
. Participants with acute illness (this does not include minor illnesses such as diarrhoea or mild upper respiratory tract infection) or body temperature ≥38.0ºC on Day 1 will be excluded from randomization at that time but may be rescheduled for randomization and/or vaccination at a later date.
. Participants who cannot communicate reliably with the investigator
. Pregnant or breastfeeding
. Women of childbearing potential who are not on an effective long-acting contraceptive method for at least 21 days prior to enrollment (date of signed informed consent) and not intending to continue contraception for up to 9 months post first vaccination.(See Section 10.5.1 below)
. Prior administration of an investigational coronavirus vaccine (for example, SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome [MERS-CoV] vaccine), except for participants of the Sisonke trial
. Prior administration of any SARS-CoV-2 vaccine boost
. Has a medical, psychiatric, or occupational condition that may pose additional risk as a result of participation, or that could interfere with safety assessments or interpretation of results according to the Investigator's judgment
. History of harmful substance or alcohol use within the past 2 years. This exclusion does not apply to cannabis use.
. Receipt of:
1. . Systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to the day of randomization (for corticosteroids, ≥20 mg/day prednisone equivalent). Topical tacrolimus is allowed if not used within 14 days prior to the day of randomization. Inhaled, nasal, and topical steroids are allowed.
2. . Intravenous blood products (red cells, platelets, immunoglobulins, monoclonal antibodies specific for SARS-CoV-2) within 3 months prior to enrollment
3. . Experimental vaccine within the past 6 months before first vaccination
4. . Any inactivated vaccines received within 14 days prior to first vaccination or planned within 14 days of first vaccination, or live attenuated vaccines received with 30 days prior to the first vaccination or planned within 30 days of the first vaccination.
. Participated in an interventional clinical study within 28 days prior to the Screening Visit (Day 1) or plans to do so while participating in this study.
. Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.

Sites / Locations

The Aurum Institute: Pretoria Clinical Research Centre
The Aurum Institute: Tembisa Clinical Research Centre, Clinic 4Recruiting
The Aurum Institute: Tembisa Clinical Research CentreRecruiting
The Aurum Institute: Gavin J Churchyard Legacy CentreRecruiting
The Aurum Institute: Rustenburg Clinical Research CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine

SARS-CoV-2 rS (CovovaxTM)

BNT162b2 (Pfizer) (Comirnaty)

Arm Description

Description: The Ad26.COV2.Sis a recombinant, replication-defective adenovirus type 26 (Ad26) vector vaccine encoding the SARS-CoV-2 spike (S) glycoprotein. Dose: The Ad26.COV2.S drug product (DP) is supplied as a single-dose or multi-dose suspension (target DP titer is 1×1011 virus particles [vp]/mL or 2×1011 vp/mL) for intramuscular (IM) injection. Dosage Form: Sterile liquid suspension for injection Colourless to slightly yellow, clear to very opalescent suspension (pH 6-6.4). Packaging: The vaccine will be provided as a multi-dose vial with 5 doses per vial with a total volume of 2.5ml. Administration: Vaccination (5x10^10 vp dose) is given as a 0.5mL intramuscular injection into the deltoid muscle in the upper arm.

Description - SARS-CoV-2 rS (CovovaxTM): is a recombinant protein nanoparticle vaccine constructed from the SARS-CoV-2 full-length spike (S) glycoprotein co-formulated with Matrix-M1 adjuvant. Dose: Each 0.5ml of SARS-CoV-2 rS consists of 5μg of a recombinant nanoparticle spike protein plus 50 μg of Matrix-M1 adjuvant. Dosage Form: Suspension for injection COVOVAX™ is colourless to slightly yellow, clear to mildly opalescent, free to practically free from visible particles. Packaging: The vaccine will be supplied as a multi-dose vial containing 10 doses per vial Administration: Vaccinations are given as a 0.5mL intramuscular injection into the deltoid muscle in the upper arm

Description: is a nucleoside-modified messenger RNA encoding the viral spike (S) glycoprotein of SARS-CoV-2. Vaccinations 30mcg (0.3mL) will be given as an intramuscular injection into the deltoid muscle in the upper arm. Dose: Each dose (0.3 mL) contains 30 micrograms of COVID-19 mRNA Vaccine. Dosage Form: White to off-white frozen suspension for Intramuscular (IM) injection Packaging: This vaccine will be supplied as a multidose vial and must be diluted with 0.9% Sodium Chloride USP before use. Each vial (0.45 mL) contains 6 doses of 0.3 mL after dilution. Administration: Comirnaty should be administered intramuscularly after dilution. Each dose must contain 0.3 mL of vaccine. The preferred site is the deltoid muscle of the upper arm

Outcomes

Primary Outcome Measures

Primary Objective and Endpoint/Outcome 1:

In HIV-infected persons, to determine whether each boost vaccine regimen adequately boosts humoral immune responses (D15), overall and by prior vaccine regimen. In this case humoral response refers to SARS CoV-2 spike RBD protein-specific binding antibody (bAb) IgG and SARS CoV-2-specific neutralizing antibody (nAb). Endpoint/Outcome 1: • Geometric mean value of SARS CoV-2 spike RBD protein-specific binding antibody (bAb) at baseline and D15, where bAb is measured from serum using an ELISA-based antibody binding assay to the SARS-CoV-2 RBD protein. The ELISA-based antibody binding assay to the SARS-CoV-2 RBD protein will be used to measure the serum bAb concentrations. The bAb concentrations will be derived from the half-maximal Effective Concentration (EC50) and the Area under the curve (AUC), and summarised as the Geometric mean value of bAb

Primary Objective and Endpoint/Outcome 2:

In HIV-infected persons, to determine whether each boost vaccine regimen adequately boosts humoral immune responses (D15), overall and by prior vaccine regimen. In this case humoral response refers to SARS CoV-2 spike RBD protein-specific binding antibody (bAb) IgG and SARS CoV-2-specific neutralizing antibody (nAb). Endpoint/Outcome 2: • Geometric mean value of SARS CoV-2-specific neutralizing antibody (nAb) at baseline and D15 where nAb is measured from serum using a pseudovirus neutralizing assay. The SARS-CoV-2 VSV pseudotyped virus-based assay will be used measure the serum nAb concentrations. The nAb concentrations will be derived from Half-maximal inhibitory concentration (IC50), and summarised as the Geometric mean value of nAb

Secondary Outcome Measures

Secondary Objective 1 and Endpoint/Outcome 1:

In HIV-infected persons, to compare between Vaccine Arms (A, B, or C) humoral immune responses post boost vaccination (Day 15 and Months 6 and 12), overall and stratified by primary vaccination regimen, duration since primary vaccination, and age group. In this case humoral response refers to SARS CoV-2 spike RBD protein-specific binding antibody (bAb) and SARS CoV-2-specific neutralizing antibody (nAb). Endpoint/Outcome 1: • The ELISA-based antibody binding assay to the SARS-CoV-2 RBD protein will be used to measure the serum bAb concentrations. Geometric mean value of SARS CoV-2 spike RBD protein-specific binding antibody (bAb) at Day 15 and Months 6 and 12 is determined from the half-maximal Effective Concentration (EC50) and the Area under the curve (AUC)

Secondary Objective 1 and Endpoint/Outcome 2:

In HIV-infected persons, to compare between Vaccine Arms (A, B, or C) humoral immune responses post boost vaccination (Day 15 and Months 6 and 12), overall and stratified by primary vaccination regimen, duration since primary vaccination, and age group. In this case humoral response refers to SARS CoV-2 spike RBD protein-specific binding antibody (bAb) and SARS CoV-2-specific neutralizing antibody (nAb). Endpoint/Outcome 2: • The SARS-CoV-2 VSV pseudotyped virus-based assay will be used measure the serum nAb concentrations. Geometric mean value of SARS CoV-2-specific neutralizing antibody (nAb) at Day 15 and Months 6 and 12 as measured by the half-maximal inhibitory concentration (IC50)

Secondary Objective 2 and Endpoint/Outcome 1:

In HIV-infected persons, to describe the safety of each COVID-19 boost vaccine regimen. In this study safety is measured by moderate or severe solicited local and systemic adverse event (AE), serious adverse events (SAEs), medically attended AEs (MAAEs), or adverse events of special interest (AESI) Endpoint/Outcome 1: • Solicited local and systemic adverse events (AEs) within 7 days after each vaccine dose. The proportion of participants with at least one moderate or severe solicited local and systemic adverse event (AE) within 7 days after each vaccine dose, presented by study arm

Secondary Objective 2 and Endpoint/Outcome 2:

In HIV-infected persons, to describe the safety of each COVID-19 boost vaccine regimen. In this study safety is measured by moderate or severe solicited local and systemic adverse event (AE), serious adverse events (SAEs), medically attended AEs (MAAEs), or adverse events of special interest (AESI) Endpoint/Outcome 2: • Unsolicited AEs within 28 days after each vaccine dose. The proportion of participants with at least one unsolicited AE within 28 days after each vaccine dose presented by study arm and stratified per study group

Secondary Objective 2 and Endpoint/Outcome 3:

In HIV-infected persons, to describe the safety of each COVID-19 boost vaccine regimen. In this study safety is measured by moderate or severe solicited local and systemic adverse event (AE), serious adverse events (SAEs), medically attended AEs (MAAEs), or adverse events of special interest (AESI) Endpoint/Outcome 3: • The frequency of Serious adverse events (SAEs), medically attended AEs (MAAEs), or adverse events of special interest (AESI) from the first vaccine dose for up to 12 months after the last vaccine dose, presented by study arm and stratified per study group

Secondary Objective 3 and Endpoint/Outcome 1:

In HIV-infected persons, to compare between Vaccine Arms (A, B, or C) the cellular immunogenicity post boost (D15 and months six and twelve), overall and stratified by primary vaccination regimen, duration since primary vaccination and age group. In this study cellular immunogenicity is measured by SARS CoV-2 specific CD4+ and CD8+ T-cell responses using ELISpot and flow cytometry from peripheral blood mononuclear cells. Endpoint/Outcome 1: • The SARS CoV-2 specific T-cell responses will be measured by the IFN-gamma ELISpot assay. In this study the outcome measure for IFN-gamma ELISpot is Spot Forming Units per 10^6 cells.

Secondary Objective 3 and Endpoint/Outcome 2:

In HIV-infected persons, to compare between Vaccine Arms (A, B, or C) the cellular immunogenicity post boost (D15 and months six and twelve), overall and stratified by primary vaccination regimen, duration since primary vaccination and age group. In this study cellular immunogenicity is measured by SARS CoV-2 specific CD4+ and CD8+ T-cell responses using ELISpot and flow cytometry from peripheral blood mononuclear cells. Endpoint/Outcome 2: • The SARS CoV-2 specific CD4+ and CD8+ T-cell response will be measured by flow cytometry. The outcome measure for flow cytometry is the percentage T cell responses for the following cytokines: IFN-γ, IL-2, TNF-α and Granzyme B

Full Information

NCT ID

NCT05515042

First Posted

July 11, 2022

Last Updated

August 23, 2022

Sponsor

The Aurum Institute NPC

Collaborators

Coalition for Epidemic Preparedness Innovations

1. Study Identification

Unique Protocol Identification Number

NCT05515042

Brief Title

Phase 2a Trial to Evaluate Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected/Uninfected Adults.

Acronym

AUR1-8-341

Official Title

A Phase 2a Trial to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected and HIV-uninfected Adults.

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Recruiting

Study Start Date

July 25, 2022 (Actual)

Primary Completion Date

July 31, 2023 (Anticipated)

Study Completion Date

July 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The Aurum Institute NPC

Collaborators

Coalition for Epidemic Preparedness Innovations

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a multicenter, randomized, observer blind clinical trial. A total of 750 evaluable HIV-infected (660) and HIV-uninfected (90) adult participants meeting all entry criteria (all inclusion and no exclusion criteria) will be enrolled in 3 treatment strategies in 3 participant groups dependent on prior vaccination with a single dose Janssen (Group 1), 2 doses of Pfizer (Group 2) or no prior COVID-19 vaccination with evidence of prior SARS-CoV-2 infection (Group 3) .A total of 300 participants per group will be enrolled in Groups 1 and 2 (255 HIV-infected and 45 HIV-uninfected per group), and 150 HIV-infected, unvaccinated participants in Group 3. Each treatment regimen (Vaccine Arm: A, B or C) will evaluate 250 participants. Groups 1 and 2 will enrol 85 HIV-infected and 15 HIV-uninfected per vaccine arm.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID-19

Keywords

Vaccines

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

This is a multicenter, randomized, observer blind clinical trial. A total of 750 evaluable HIV-infected (660) and HIV-uninfected (90) adult participants meeting all entry criteria (all inclusion and no exclusion criteria) will be enrolled in 3 treatment strategies in 3 participant groups dependent on prior vaccination with a single dose Janssen (Group 1), 2 doses of Pfizer (Group 2) or no prior COVID-19 vaccination with evidence of prior SARS-CoV-2 infection (Group 3). A total of 300 participants per group will be enrolled in Groups 1 and 2 (255 HIV-infected and 45 HIV-uninfected per group), and 150 HIV-infected, unvaccinated participants in Group 3. Each treatment regimen (Vaccine Arm: A, B or C) will evaluate 250 participants. Groups 1 and 2 will enrol 85 HIV-infected and 15 HIV-uninfected per vaccine arm.

Masking

ParticipantInvestigator

Masking Description

Participants, investigators, and site staff (except for site pharmacists) will be blinded to participant treatment group assignment for the full duration of the study. Study product assignments are accessible to the site pharmacists and unblinded monitors who are required to know this information in order to ensure proper trial conduct. Any discussion of study product assignment between pharmacy staff and any other staff is prohibited. The DSMB members may be unblinded on request to treatment assignment, in order to conduct review of trial safety data.

Allocation

Randomized

Enrollment

750 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine

Arm Type

Active Comparator

Arm Description

Arm Title

SARS-CoV-2 rS (CovovaxTM)

Arm Type

Active Comparator

Arm Description

Arm Title

BNT162b2 (Pfizer) (Comirnaty)

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine, SARS-CoV-2 rS (CovovaxTM), BNT162b2 (Pfizer)

Intervention Description

As included in arm/group descriptions

Primary Outcome Measure Information:

Title

Primary Objective and Endpoint/Outcome 1:

Description

Time Frame

14 Months

Title

Primary Objective and Endpoint/Outcome 2:

Description

In HIV-infected persons, to determine whether each boost vaccine regimen adequately boosts humoral immune responses (D15), overall and by prior vaccine regimen. In this case humoral response refers to SARS CoV-2 spike RBD protein-specific binding antibody (bAb) IgG and SARS CoV-2-specific neutralizing antibody (nAb). Endpoint/Outcome 2: • Geometric mean value of SARS CoV-2-specific neutralizing antibody (nAb) at baseline and D15 where nAb is measured from serum using a pseudovirus neutralizing assay. The SARS-CoV-2 VSV pseudotyped virus-based assay will be used measure the serum nAb concentrations. The nAb concentrations will be derived from Half-maximal inhibitory concentration (IC50), and summarised as the Geometric mean value of nAb

Time Frame

14 Months

Secondary Outcome Measure Information:

Title

Secondary Objective 1 and Endpoint/Outcome 1:

Description

Time Frame

14 Months

Title

Secondary Objective 1 and Endpoint/Outcome 2:

Description

In HIV-infected persons, to compare between Vaccine Arms (A, B, or C) humoral immune responses post boost vaccination (Day 15 and Months 6 and 12), overall and stratified by primary vaccination regimen, duration since primary vaccination, and age group. In this case humoral response refers to SARS CoV-2 spike RBD protein-specific binding antibody (bAb) and SARS CoV-2-specific neutralizing antibody (nAb). Endpoint/Outcome 2: • The SARS-CoV-2 VSV pseudotyped virus-based assay will be used measure the serum nAb concentrations. Geometric mean value of SARS CoV-2-specific neutralizing antibody (nAb) at Day 15 and Months 6 and 12 as measured by the half-maximal inhibitory concentration (IC50)

Time Frame

14 Months

Title

Secondary Objective 2 and Endpoint/Outcome 1:

Description

Time Frame

14 Months

Title

Secondary Objective 2 and Endpoint/Outcome 2:

Description

In HIV-infected persons, to describe the safety of each COVID-19 boost vaccine regimen. In this study safety is measured by moderate or severe solicited local and systemic adverse event (AE), serious adverse events (SAEs), medically attended AEs (MAAEs), or adverse events of special interest (AESI) Endpoint/Outcome 2: • Unsolicited AEs within 28 days after each vaccine dose. The proportion of participants with at least one unsolicited AE within 28 days after each vaccine dose presented by study arm and stratified per study group

Time Frame

14 Months

Title

Secondary Objective 2 and Endpoint/Outcome 3:

Description

In HIV-infected persons, to describe the safety of each COVID-19 boost vaccine regimen. In this study safety is measured by moderate or severe solicited local and systemic adverse event (AE), serious adverse events (SAEs), medically attended AEs (MAAEs), or adverse events of special interest (AESI) Endpoint/Outcome 3: • The frequency of Serious adverse events (SAEs), medically attended AEs (MAAEs), or adverse events of special interest (AESI) from the first vaccine dose for up to 12 months after the last vaccine dose, presented by study arm and stratified per study group

Time Frame

14 Months

Title

Secondary Objective 3 and Endpoint/Outcome 1:

Description

Time Frame

14 Months

Title

Secondary Objective 3 and Endpoint/Outcome 2:

Description

In HIV-infected persons, to compare between Vaccine Arms (A, B, or C) the cellular immunogenicity post boost (D15 and months six and twelve), overall and stratified by primary vaccination regimen, duration since primary vaccination and age group. In this study cellular immunogenicity is measured by SARS CoV-2 specific CD4+ and CD8+ T-cell responses using ELISpot and flow cytometry from peripheral blood mononuclear cells. Endpoint/Outcome 2: • The SARS CoV-2 specific CD4+ and CD8+ T-cell response will be measured by flow cytometry. The outcome measure for flow cytometry is the percentage T cell responses for the following cytokines: IFN-γ, IL-2, TNF-α and Granzyme B

Time Frame

14 Months

Other Pre-specified Outcome Measures:

Title

Exploratory Objective 1 and Endpoint/Outcome 1:

Description

To examine the immunologic imprint and pre-existing cross-reactive T-cell memory on vaccine induced antibody and T-cell responses in HIV-infected and HIV-uninfected participants. The coronavirus antigen microarray (CoVAM), Human virome-wide peptide library (PepSeq) and the Activation-induced T-cell marker assay (AIM) assay will be used to measure the immunologic imprint and pre-existing of cross-reactive T-cell memory on vaccine induced antibody and T-cell responses. Endpoint/Outcome 1: • Influence of pre-existing immunity on vaccine induced antibody and T-cell responses using coronavirus antigen microarray (CoVAM). The CoVAM outcome measure is the composite SARS-CoV-2 IgG mean fluorescence intensity (MFI) +/-95% CI

Time Frame

14 Months

Title

Exploratory Objective 1 and Endpoint/Outcome 2:

Description

To examine the immunologic imprint and pre-existing cross-reactive T-cell memory on vaccine induced antibody and T-cell responses in HIV-infected and HIV-uninfected participants. The coronavirus antigen microarray (CoVAM), Human virome-wide peptide library (PepSeq) and the Activation-induced T-cell marker assay (AIM) assay will be used to measure the immunologic imprint and pre-existing of cross-reactive T-cell memory on vaccine induced antibody and T-cell responses. Endpoint/Outcome 2: • Influence of pre-existing immunity on vaccine induced antibody and T-cell responses using coronavirus antigen microarray PepSeq assay. The PepSeq outcome measure ins the descriptive analysis of the frequency, kinetics and type of conserved, non-conserved and cross-reactive spike-specific epitopes

Time Frame

14 Months

Title

Exploratory Objective 1 and Endpoint/Outcome 3:

Description

To examine the immunologic imprint and pre-existing cross-reactive T-cell memory on vaccine induced antibody and T-cell responses in HIV-infected and HIV-uninfected participants. The coronavirus antigen microarray (CoVAM), Human virome-wide peptide library (PepSeq) and the Activation-induced T-cell marker assay (AIM) assay will be used to measure the immunologic imprint and pre-existing of cross-reactive T-cell memory on vaccine induced antibody and T-cell responses. Endpoint/Outcome 3: • The activation status of CD4+ and CD8+ T-cells using the AIM assay at baseline. The AIM assay outcome measure is the Geometric mean +/- 95% CI of AIM+ (OX40+CD137+) CD4+ and (CD69+CD137+) CD8+ T cells

Time Frame

14 Months

Title

Exploratory Objective 2 and Endpoint/Outcome 1:

Description

To describe COVID-19 infection and disease in trial participants. Endpoint/Outcome 1: • Number of participants with SARS CoV-2 infection (nucleocapsid antibody positive) will be determined using the SARS-CoV-2 Real Time (RT) PCR assay. The Thermofischer TaqPathTM COVID-19 CE-IVD RT-PCR will used to determine SARS CoV-2 infection. Participants with a positive RT PCR result will be regarded as SARS CoV-2 infected. The outcome measure of the RT PCR assay is the cycle threshold (Ct) values.

Time Frame

14 Months

Title

Exploratory Objective 2 and Endpoint/Outcome 2:

Description

To describe COVID-19 infection and disease in trial participants. Endpoint/Outcome 2: • Number of participants with COVID-19 disease (RT PCR positive) will be determined using the nucleocapsid-specific binding antibody. In this case the Abbott SARS-CoV-2 IgG chemiluminescent assay will be used to measure the serum nucleocapsid antibody concentrations. Participants with a positive a nucleocapsid antibody result will be regarded as SARS CoV-2 infected. The outcome measure of the Abbott SARS-CoV-2 IgG chemiluminescent assay is the N SARS-CoV-2 N protein IgG Index S/C.

Time Frame

14 Months

Title

Exploratory Objective 3 and Endpoint/Outcome:

Description

To characterize B-cell function and specificity in HIV-infected and HIV-uninfected participants post vaccination. In this case B-cell sorting and antibody sequencing will be used to determine the immunogenetic profiles of antibody lineages. Differences in the immunogenetic profiles of antibody lineages (including germline gene usage, percent somatic hypermutation and CDRH3 length), Clonal expansion and affinity maturation of memory B cells, Convergence of SARS-CoV-2 directed "public" antibody repertoires shared by participants. Endpoint/Outcome: The outcome will be B-cell germline gene usage, percent (%) somatic hypermutation and CDRH3 length

Time Frame

14 Months

Title

Exploratory Objective 4 and Endpoint/Outcome 1:

Description

To compare humoral and cellular immune responses post boost vaccination (Day 15 and months 6 and 12) among participants with or without prior SARS-CoV-2 infection in HIV-infected and HIV-uninfected participants, overall and by Vaccine Arm. Humoral response refers to SARS CoV-2 spike RBD protein-specific binding antibody (bAb) IgG and SARS CoV-2-specific neutralizing antibody (nAb). Endpoint/Outcome 1: • Geometric mean value of SARS CoV-2 spike RBD protein-specific binding antibody (bAb) at baseline and D15, month 6 and month 12 where bAb is measured from serum using an ELISA-based antibody binding assay to the SARS-CoV-2 RBD protein. Cellular immunogenicity is measured by SARS CoV-2 specific CD4+ and CD8+ T-cell responses using ELISpot and flow cytometry from peripheral blood mononuclear cells

Time Frame

14 Months

Title

Exploratory Objective 4 and Endpoint/Outcome 2:

Description

To compare humoral and cellular immune responses post boost vaccination (Day 15 and months 6 and 12) among participants with or without prior SARS-CoV-2 infection in HIV-infected and HIV-uninfected participants, overall and by Vaccine Arm. Humoral response refers to SARS CoV-2 spike RBD protein-specific binding antibody (bAb) IgG and SARS CoV-2-specific neutralizing antibody (nAb). Endpoint/Outcome 2: • Geometric mean value of SARS CoV-2-specific neutralizing antibody (nAb) at baseline, D15, month 6 and month 12 where nAb is measured from serum using a pseudovirus neutralizing assay. Cellular immunogenicity is measured by SARS CoV-2 specific CD4+ and CD8+ T-cell responses using ELISpot and flow cytometry from peripheral blood mononuclear cells

Time Frame

14 Months

Title

Exploratory Objective 4 and Endpoint/Outcome 3:

Description

Time Frame

14 Months

Title

Exploratory Objective 5 and Endpoint/Outcome 1:

Description

To describe among HIV-infected, unvaccinated, participants with prior SARS-C0V-2 infection, humoral and cellular immune responses post boost vaccination (Day 15 and months 6 and 12), overall and by Vaccine Arm. Humoral response refers to SARS CoV-2 spike RBD protein-specific binding antibody (bAb) IgG and SARS CoV-2-specific neutralizing antibody (nAb). Cellular immunogenicity is measured by SARS CoV-2 specific CD4+ and CD8+ T-cell responses using ELISpot and flow cytometry from peripheral blood mononuclear cells. Endpoint/Outcome 1: • Geometric mean value of SARS CoV-2 spike RBD protein-specific binding antibody (bAb) at baseline and D15, month 6 and month 12 where bAb is measured from serum using an ELISA-based antibody binding assay to the SARS-CoV-2 RBD protein. Cellular immunogenicity is measured by SARS CoV-2 specific CD4+ and CD8+ T-cell responses using ELISpot and flow cytometry from peripheral blood mononuclear cells.

Time Frame

14 Months

Title

Exploratory Objective 5 and Endpoint/Outcome 2:

Description

To describe among HIV-infected, unvaccinated, participants with prior SARS-C0V-2 infection, humoral and cellular immune responses post boost vaccination (Day 15 and months 6 and 12), overall and by Vaccine Arm. Humoral response refers to SARS CoV-2 spike RBD protein-specific binding antibody (bAb) IgG and SARS CoV-2-specific neutralizing antibody (nAb). Cellular immunogenicity is measured by SARS CoV-2 specific CD4+ and CD8+ T-cell responses using ELISpot and flow cytometry from peripheral blood mononuclear cells. Endpoint/Outcome 2: • Geometric mean value of SARS CoV-2-specific neutralizing antibody (nAb) at baseline, D15, month 6 and month 12 where nAb is measured from serum using a pseudovirus neutralizing assay. Cellular immunogenicity is measured by SARS CoV-2 specific CD4+ and CD8+ T-cell responses using ELISpot and flow cytometry from peripheral blood mononuclear cells.

Time Frame

14 Months

Title

Exploratory Objective 5 and Endpoint/Outcome 3:

Description

To describe among HIV-infected, unvaccinated, participants with prior SARS-C0V-2 infection, humoral and cellular immune responses post boost vaccination (Day 15 and months 6 and 12), overall and by Vaccine Arm. Humoral response refers to SARS CoV-2 spike RBD protein-specific binding antibody (bAb) IgG and SARS CoV-2-specific neutralizing antibody (nAb). Cellular immunogenicity is measured by SARS CoV-2 specific CD4+ and CD8+ T-cell responses using ELISpot and flow cytometry from peripheral blood mononuclear cells. Endpoint/Outcome 3: • Mean SARS CoV-2 specific CD4+ and CD8+ T-cell responses by intracellular cytokine staining at Day 15 and months 6 and 12

Time Frame

14 Months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

100 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: . Adult male or female aged 18 and above at the time of written informed consent . Willing and able to give written informed consent . HIV-infected persons on ART for at least three months prior to enrollment, or HIV-uninfected persons . Able to provide evidence of completing a primary COVID-19 vaccination regimen with either a single dose of Ad26.COV2.S or two doses of BNT162b2 at least two months prior to enrolment, or HIV-infected with no prior COVID-19 vaccination and evidence of prior SAR-CoV-2 infection . Residing in the vicinity of the clinical trial site and planning to remain in the area of the study for 12months . Able and willing to participate for the duration of the study visits and follow-up . Willing to provide verifiable identification (eg. Identity document, passport) at study entry and follow-up visits Exclusion Criteria: . Positive SARS-CoV-2 PCRor antigen detection test . Persons with undocumented HIV status . HIV-infected persons with CD4count <1 00 cells/mm3and/or Viral Load > 1000 copies/ml . Known allergy or history of anaphylaxis or other serious adverse reactions to specific COVID-19 vaccine constituents . History of capillary leak syndrome, thrombosis with thrombocytopenia syndrome (TTS), heparin-induced thrombocytopenia (HIT), history of any neurological disorders or seizures including Guillain-Barré syndrome, with the exception of febrile seizures during childhood . Participants with acute illness (this does not include minor illnesses such as diarrhoea or mild upper respiratory tract infection) or body temperature ≥38.0ºC on Day 1 will be excluded from randomization at that time but may be rescheduled for randomization and/or vaccination at a later date. . Participants who cannot communicate reliably with the investigator . Pregnant or breastfeeding . Women of childbearing potential who are not on an effective long-acting contraceptive method for at least 21 days prior to enrollment (date of signed informed consent) and not intending to continue contraception for up to 9 months post first vaccination.(See Section 10.5.1 below) . Prior administration of an investigational coronavirus vaccine (for example, SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome [MERS-CoV] vaccine), except for participants of the Sisonke trial . Prior administration of any SARS-CoV-2 vaccine boost . Has a medical, psychiatric, or occupational condition that may pose additional risk as a result of participation, or that could interfere with safety assessments or interpretation of results according to the Investigator's judgment . History of harmful substance or alcohol use within the past 2 years. This exclusion does not apply to cannabis use. . Receipt of: . Systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to the day of randomization (for corticosteroids, ≥20 mg/day prednisone equivalent). Topical tacrolimus is allowed if not used within 14 days prior to the day of randomization. Inhaled, nasal, and topical steroids are allowed. . Intravenous blood products (red cells, platelets, immunoglobulins, monoclonal antibodies specific for SARS-CoV-2) within 3 months prior to enrollment . Experimental vaccine within the past 6 months before first vaccination . Any inactivated vaccines received within 14 days prior to first vaccination or planned within 14 days of first vaccination, or live attenuated vaccines received with 30 days prior to the first vaccination or planned within 30 days of the first vaccination. . Participated in an interventional clinical study within 28 days prior to the Screening Visit (Day 1) or plans to do so while participating in this study. . Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Dr Vaneshree Govender, MBBCh

Phone

+27 84 759 6461

VGovender@auruminstitute.org

First Name & Middle Initial & Last Name or Official Title & Degree

Ms Tania Adonis, B Psychology

Phone

+27 76 266 8653

tadonis@auruminstitute.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Prof Gavin Churchyard, PhD

Organizational Affiliation

The Aurum Institute NPC

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Aurum Institute: Pretoria Clinical Research Centre

City

Pretoria

State/Province

Gauteng

ZIP/Postal Code

0087

Country

South Africa

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dr Esme Venter, MBChB

Phone

+27 82 576 2484

eventer@auruminstitute.org

First Name & Middle Initial & Last Name & Degree

Ms Tania Adonis, B Psychology

Phone

+27 76 266 8653

tadonis@auruminstitute.org

First Name & Middle Initial & Last Name & Degree

Dr Esme Venter, MBChB

First Name & Middle Initial & Last Name & Degree

Dr Lelanie van Zyl, MBChB

First Name & Middle Initial & Last Name & Degree

Dr Zwelethu Desmond Zwane, MBChB

Facility Name

The Aurum Institute: Tembisa Clinical Research Centre, Clinic 4

City

Tembisa

State/Province

Gauteng

ZIP/Postal Code

1632

Country

South Africa

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dr Kathryn Mngadi, MBChB, MPhil

Phone

+27 82 574 4541

kmngadi@auruminstitute.org

First Name & Middle Initial & Last Name & Degree

Ms Tania Adonis, B Psychology

Phone

+27 76 266 8653

tadonis@auruminstitute.org

First Name & Middle Initial & Last Name & Degree

Dr Kathryn Mngadi, MBChB, MPhil

First Name & Middle Initial & Last Name & Degree

Dr Anja Henning, MBChB

First Name & Middle Initial & Last Name & Degree

Dr Shanal Nair, MBChB

Facility Name

The Aurum Institute: Tembisa Clinical Research Centre

City

Tembisa

State/Province

Gauteng

ZIP/Postal Code

1632

Country

South Africa

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dr Modulakgotla Sebe, MBChB

Phone

27-87-1351645

msebe@auruminstitute.org

First Name & Middle Initial & Last Name & Degree

Ms Tania Adonis, B Psychology

Phone

+27 76 266 8653

tadonis@auruminstitute.org

Facility Name

The Aurum Institute: Gavin J Churchyard Legacy Centre

City

Klerksdorp

State/Province

North West Province

ZIP/Postal Code

2571

Country

South Africa

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dr James Craig Innes, MBChB

Phone

+27 82 336 9626

cinnes@auruminstitute.org

First Name & Middle Initial & Last Name & Degree

Ms Tania Adonis, B Psychology

Phone

+27 76 266 8653

tadonis@auruminstitute.org

First Name & Middle Initial & Last Name & Degree

Dr James Craig Innes, MBChB

First Name & Middle Initial & Last Name & Degree

Dr Raesibe Agnes Pearl Selepe, MBChB

First Name & Middle Initial & Last Name & Degree

Dr Oteng Letlape, MBBCH

First Name & Middle Initial & Last Name & Degree

Dr Mgcini Moyo, MBChB

Facility Name

The Aurum Institute: Rustenburg Clinical Research Centre

City

Rustenburg

State/Province

North-West Province

ZIP/Postal Code

0299

Country

South Africa

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mr William Brumskine, MBChB

Phone

+27 72 334 3575

wbrumskine@auruminstitute.org

First Name & Middle Initial & Last Name & Degree

Ms Tania Adonis, B Psychology

Phone

+27 76 266 8653

tadonis@auruminstitute.org

First Name & Middle Initial & Last Name & Degree

Mr William Brumskine, MBChB

First Name & Middle Initial & Last Name & Degree

Dr Ni Ni Sein, MBBS

First Name & Middle Initial & Last Name & Degree

Dr Melissa Senne, MBChB

First Name & Middle Initial & Last Name & Degree

Dr Megan Easton, MBChB

First Name & Middle Initial & Last Name & Degree

Dr Johanna Alida Baumgarten, MBChB

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The applicants are committed to the open science practice and will ensure rapid sharing of research results with scientific communities, policy makers and public of interest through peer-reviewed journal, national and international conferences. All publications will adopt open access principles based on the gold and green models. The study team will prepare a dissemination plan for study updates and results dissemination to high level stakeholders (IECs, Ministries of Health, NDR, government officials and international stakeholders). Study updates will be communicated to participants, CAB, study staff and other key stakeholders (trial networks, health advocates) timeously. The proposed trial will be registered at the Clinicaltrials.gov and South African Clinical Trials Register (SANCTR). Investigators will write and review the interim analysis and final analysis reports and publications.

IPD Sharing Time Frame

Quarter 4 2023

IPD Sharing Access Criteria

Publication in Open Access Repositories will ensure that publications are publicly discoverable, accessible, and re-usable as soon as possible. After appropriate data clearance, and where appropriate IP arrangements have been made, we will make use of pre-print archives such as bioRxiv/medRxiv or Zenodo to stimulate immediate exchange and discussion of results, prior to peer-reviewed publication. Any further manuscripts, abstracts, press releases and publications that may arise from the study will be reviewed by all investigators. A full publication plan will be developed with all investigators and the funder once the study results are available.

Learn more about this trial

Phase 2a Trial to Evaluate Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected/Uninfected Adults.

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