Clinical trial NCT05087368: Immunogenicity and Safety of Heterologous and Homologous Boosting With ChAdOx1-S and CoronaVac or a Formulation of SCB-2019 (COVID-19)
Official title: An Observer-blinded, Randomized, Controlled, Phase 2 Study to Evaluate the Immunogenicity and Safety of Heterologous and Homologous Boosting With ChAdOx1-S and CoronaVac COVID-19 Vaccines or One Formulation of Clover Adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine (SCB-2019) Determined in a lead-in Formulation Finding in Healthy Adults.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Covid19
Keywords: Covid19
Immunogenicity
Vaccines
Lead sponsor: D'Or Institute for Research and Education
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
name: Instituto Fernandes Figueira
First posted: 2021-10-21
Enrollment: 520
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Controlled, observer-blinded, Phase 2 Study
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female ≥18 years of age.
2. Individuals are willing and able to comply with study requirements, including all scheduled visits, vaccinations, laboratory tests, and other study procedures.
3. Individuals are willing and able to give an informed consent, prior to screening.
4. Individuals who:

   • Received two dose of ChAdOx1-S vaccine 6 months (± 4 weeks) (Groups 1-4 of Stage 1 and Groups 5-7 of Stage 2) or CoronaVac 6 months (± 4 weeks) (Groups 8-10 of Stage 2) prior to recruitment in this study
5. Healthy participants or participants with pre-existing medical conditions who are in a stable medical condition. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment.
6. Female participants are eligible to participate in the study if not pregnant, not breastfeeding, and at least 1 of the following criteria apply:

   * Women of non-childbearing potential;
   * Women of childbearing potential (WOCBP) must have a negative urine pregnancy test prior to study vaccination. A confirmatory serum pregnancy test may be conducted at the investigator's discretion. They must be using a highly effective licensed method of birth control for 30 days prior to the first vaccination and must agree to continue such precautions during the study until 90 days after the last study vaccination.
7. Male participants must agree to employ acceptable contraception from the day of first dose of the study vaccine/comparator until 6 months after the last dose of the study vaccine/comparator and also refrain from donating sperm during this period.

Primary outcomes:
measure: Immunogenicity - Stage 1
timeFrame: Day 1
measure: Immunogenicity - Stage 1
timeFrame: Day 15
measure: Immunogenicity - Stage 1
timeFrame: Day 29
measure: Immunogenicity - Stage 2
timeFrame: Day 1
measure: Immunogenicity - Stage 2
timeFrame: Day 15
measure: Immunogenicity - Stage 2
timeFrame: Day 180
measure: Immunogenicity - Stage 2
timeFrame: Day 360
Secondary outcomes:
measure: Reactogenicity
timeFrame: During 7 days after study vaccination
measure: Reactogenicity
timeFrame: After 28 days after study vaccination
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: Rio De Grande Do Sul
city: Rio De Janeiro
country: Brazil
facility: Hospital Gloria D'or
state: Rio De
city: Natal
country: Brazil
facility: Centro de Estudos e Pesquisa em Moléstias Infecciosas (CEPCLIN)
state: Rio Grande Do Norte
Study officials:
affiliation: Global Health - Oxford University Siena University
name: Sue Ann Clemens Costa Clemens, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Costa Clemens SA, Milan EP, Sprinz E, Neto JC, Pacciarini F, Li P, Chen HL, Smolenov I, Pollard A, Clemens R. Homologous and Heterologous Boosting of the Chadox1-S1-S COVID-19 Vaccine With the SCB-2019 Vaccine Candidate: A Randomized, Controlled, Phase 2 Study. Open Forum Infect Dis. 2022 Aug 16;9(8):ofac418. doi: 10.1093/ofid/ofac418. eCollection 2022 Aug.