Phase 2a Trial to Evaluate Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected/Uninfected Adults.
AUR1-8-341
A Phase 2a Trial to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected and HIV-uninfected Adults.
2 other identifiers
interventional
694
1 country
5
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 covid19
Started Jul 2022
Longer than P75 for phase_2 covid19
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 11, 2022
CompletedStudy Start
First participant enrolled
July 25, 2022
CompletedFirst Posted
Study publicly available on registry
August 25, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2024
CompletedJuly 15, 2024
July 1, 2024
1.9 years
July 11, 2022
July 12, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
14 Months
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
14 Months
Secondary Outcomes (7)
Secondary Objective 1 and Endpoint/Outcome 1:
14 Months
Secondary Objective 1 and Endpoint/Outcome 2:
14 Months
Secondary Objective 2 and Endpoint/Outcome 1:
14 Months
Secondary Objective 2 and Endpoint/Outcome 2:
14 Months
Secondary Objective 2 and Endpoint/Outcome 3:
14 Months
- +2 more secondary outcomes
Other Outcomes (12)
Exploratory Objective 1 and Endpoint/Outcome 1:
14 Months
Exploratory Objective 1 and Endpoint/Outcome 2:
14 Months
Exploratory Objective 1 and Endpoint/Outcome 3:
14 Months
- +9 more other outcomes
Study Arms (3)
Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine
ACTIVE COMPARATORDescription: 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.
SARS-CoV-2 rS (CovovaxTM)
ACTIVE COMPARATORDescription - 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
BNT162b2 (Pfizer) (Comirnaty)
ACTIVE COMPARATORDescription: 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
Interventions
As included in arm/group descriptions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- 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
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
The Aurum Institute: Pretoria Clinical Research Centre
Pretoria, Gauteng, 0087, South Africa
The Aurum Institute: Tembisa Clinical Research Centre, Clinic 4
Tembisa, Gauteng, 1632, South Africa
The Aurum Institute: Tembisa Clinical Research Centre
Tembisa, Gauteng, 1632, South Africa
The Aurum Institute: Gavin J Churchyard Legacy Centre
Klerksdorp, North West, 2571, South Africa
The Aurum Institute: Rustenburg Clinical Research Centre
Rustenburg, North West, 0299, South Africa
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Prof Gavin Churchyard, PhD
The Aurum Institute NPC
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Masking Details
- 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.
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 11, 2022
First Posted
August 25, 2022
Study Start
July 25, 2022
Primary Completion
June 30, 2024
Study Completion
December 31, 2024
Last Updated
July 15, 2024
Record last verified: 2024-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- Quarter 4 2023
- 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.
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.