Immunogenicity and Safety of Heterologous and Homologous Boosting With ChAdOx1-S and CoronaVac or a Formulation of SCB-2019 (COVID-19)

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

520 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-01

Study Completion Date

2022-04-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

SARS-CoV-2 is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, collectively called coronavirus disease-19 (COVID-19). SARS-CoV-2 has a high transmission rate, and severe cases of COVID-19 require admission to hospital intensive care units with the need for mechanical ventilation and associated high mortality. Currently cases continue to rise in many countries as the 'second and third waves' of SARS-CoV-2 infection evolve.

The authorized vaccines and most vaccines in development are focused on the major antigenic target of the virus, the SARS-CoV-2 spike (S) protein. Authorization was granted in Brazil by ANVISA for the Fiocruz/Oxford-AstraZeneca ChAdOx1-S COVID-19 vaccine as a 2-dose homologous vaccination regimen, 28- to 84-days apart. Emergency Use Authorization (EUA) was also granted for Sinovac Biotech's CoronaVac vaccine as a 2-dose homologous vaccination regimen, 28 days apart. Further vaccines, using different platforms are approved or expected to be approved for use against SARS-CoV-2. Most of the vaccines are expected to be authorized as 2-dose, homologous vaccination series.

SCB-2019 is Clover's adjuvanted recombinant SARS-CoV-2 trimeric S-protein subunit vaccine. The SCB-2019 antigen includes SARS-CoV-2 S protein as a trimer fused to Trimer-Tag and is produced in Chinese hamster ovary cells (CHO). SCB-2019 preserves the native trimeric structure of S-protein in the prefusion form and induces neutralizing antibodies to SARS-CoV-2. Trimer-Tag is derived from the fully-human C-propeptide domain of pro-collagen and is capable of self-trimerization, thus fusing any biologically-active proteins in-frame with Trimer-Tag. The resulting fusion proteins expressed in mammalian cells are secreted as disulfide bond-linked homotrimers.

The immunogenicity and safety of different dose levels (3, 9, and 30 μg) SCB-2019 vaccine, administered as 2-dose regimen 21-days apart was assessed in a phase 1 clinical study. All dose levels were well-tolerated and induced neutralizing antibodies against S protein of the SARS-CoV-2 virus. Based on the results of that study, Clover selected 30 μg of SCB-2019 in combination with the CpG 1018/alum adjuvant system for further evaluation in the phase 2/3 clinical program as having the most favorable benefit/risk profile. The pivotal study (CLO-SCB-2019-003) included approximately 30,000 healthy participants and individuals with stable pre-existing chronic medical conditions, is being conducted in multiple countries, including in Brazil. The primary purpose of that study (CLO-SCB-2019-003) is to demonstrate the safety and efficacy of SCB-2019 in the prevention of COVID-19. The study showed efficacy.

Heterologous boost vaccinations using different platforms may elicit immune responses of greater magnitude and breadth than can be achieved by priming or boosting with the same vaccine (He et al, 2021, Spencer et al., 2021). Also, given the anticipated challenges of vaccinating large proportions of the population, especially with respect to supply, out-of-stock situations, and potential misadministration, it is important for policy makers to have data on flexible vaccination schedules, where the third dose might be different from the priming platform. Protein-based adjuvanted vaccines have the advantage of being from a known and licensed technology that can produce high quantities of vaccine. Protein-based adjuvanted vaccines have also been shown to be highly immunogenic, both in the context of COVID-19 (Keech 2020; Richmond 2021) and other licensed vaccines (Skwarczynski 2016).

The purpose of this study is to compare the immunogenicity and safety of heterologous and homologous booster schedules in individuals who received ChAdOx1-S or CoronaVac vaccination previously. The study will be performed in 2 stages - Stage 1 will serve to down-select one of the SCB-2019 formulations for boosting. Stage 2 will compare homologous and heterologous booster regimens in individuals who have received a 2-dose primary vaccination series of either ChadOx1-S or of CoronaVac.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This is a phase 2, randomized, controlled, observer-blinded, multi-center study to evaluate the immunogenicity and safety of heterologous and homologous vaccination series with ChAdOx1-S or CoronaVac COVID-19 vaccines and various formulations of adjuvanted recombinant SARS-CoV-2 trimeric S-protein subunit vaccine (SCB-2019). The study will be conducted in two stages.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Covid19

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Controlled, observer-blinded, Phase 2 Study

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

This study will be observer-blind for Stage 1 and Stage 2. The participants will be blinded before receiving the study vaccination. An unblinded dosing team, not involved with study participant's evaluation, will prepare and administer the study vaccines.

The investigational product syringe will be opacified. The administration of the study vaccine will also be performed behind a closed curtain. The investigative study center personnel, as well as the sponsor personnel involved in the monitoring or conduct of the study, will be blinded to the study vaccine code.

The laboratories will also be blinded, so that associating the sample with an assigned treatment or study visit will not be possible.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Stage 1 - Formulation-finding for SCB-2019 - Group 1

In Stage 1, immunogenicity and safety of three SCB-2019 formulations will be assessed in comparison with the ChAdOx1-S vaccine, in individuals who received two doses of ChAdOx1-S, 6 months (± 4 weeks) prior to recruitment.

Participants (N=120) will be assigned to five groups for Stage 1 and receive doses as follows:

Group 1: (N=30) Day 1: SCB-2019 (9 μg) alum;

Group Type EXPERIMENTAL