Covid19Phase 2TP-SCB-2019001NCT05087368
Immunogenicity and Safety of Heterologous and Homologous Boosting With ChAdOx1-S and CoronaVac or a Formulation of SCB-2019 (COVID-19)
A Phase 2 study testing ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford-AstraZeneca), CoronaVac (Sinovac Biotech) and Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover) in people with Covid19, run by D'Or Institute for Research and Education at 3 sites in Brazil.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Covid19
- What is being tested?
- ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford-AstraZeneca), CoronaVac (Sinovac Biotech) and Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover)
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 520 participants
- Where
- 3 sitesBrazil
- Study dates
- 1 Dec 2021to 1 Apr 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female ≥18 years of age.
- Individuals are willing and able to comply with study requirements, including all scheduled visits, vaccinations, laboratory tests, and other study procedures.
- Individuals are willing and able to give an informed consent, prior to screening.
- 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
- 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.
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- 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.
- 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.
Who cannot join
None listed.
Trial locations and contacts
3 sites in 1 country.
Brazil3 sites
Centro de Estudos e Pesquisa em Moléstias Infecciosas (CEPCLIN)
Natal, Rio Grande do Norte
Eveline Milan, MD, 55 (84) 2226-0373
Eveline Milan, MD
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio de Grande Do Sul
Eduardo Sprinz, MD, 55 (51) 3359-8000
Eduardo Sprinz, MD
Hospital Gloria D'or
Rio de Janeiro, Rio de
Mayara Santos, 55 21 3883 6000
José Neto, MD
About this study
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.
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.
Read more
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.
Read the 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.
- Conditions
- Covid19
- Being tested
- ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford-AstraZeneca), CoronaVac (Sinovac Biotech), Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover)
- Keywords
- Covid19, Immunogenicity, Vaccines
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford-AstraZeneca)Biological
Heterologous and Homologous Vaccination Series with ChAdOx1-S or CoronaVac COVID-19 Vaccines and Various Formulations of Clover Adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine (SCB-2019) in Adults
CoronaVac (Sinovac Biotech)Biological
Heterologous and Homologous Vaccination Series with ChAdOx1-S or CoronaVac COVID-19 Vaccines and Various Formulations of Clover Adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine (SCB-2019) in Adults
Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover)Biological
Heterologous and Homologous Vaccination Series with ChAdOx1-S or CoronaVac COVID-19 Vaccines and Various Formulations of Clover Adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine (SCB-2019) in Adults
| Study group | Role | What they receive |
|---|---|---|
| Stage 1 - Formulation-finding for SCB-2019 - Group 1 | Experimental | 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; Receives: Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover) |
| Stage 1 - Formulation-finding for SCB-2019 - Group 2 | Experimental | 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 2: (N=30) Day 1: SCB-2019 (9 μg) CpG 1018/alum; Receives: Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover) |
| Stage 1 - Formulation-finding for SCB-2019 - Group 3 | Experimental | 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 3: (N=30) Day 1: SCB-2019 (30 μg) CpG 1018/alum; Receives: Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover) |
| Stage 1 - Formulation-finding for SCB-2019 - Group 4 | Experimental | 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 4: (N=30) Day 1: ChAdOx1-S; Receives: Biological: ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford-AstraZeneca) |
| Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 5 | Experimental | For Stage 2, immunogenicity of heterologous booster vaccination schedule (ChAdOx1-S (Group 5-7) - selected formulation of SCB-2019 or CoronaVac and CoronaVac (Group 8-10) - selected formulation of SCB-2019 or ChAdOx1) vs. a 2-dose ChAdOx1-S or CoronaVac series will be assessed.
Participants (N=400) will be randomly (2:1:1) distributed into 6 groups for Stage 2 and receive doses as follows:
Group 5: (N=100) Day 1 (boost) -SCB-2019; Receives: Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover) |
| Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 6 | Experimental | For Stage 2, immunogenicity of heterologous booster vaccination schedule (ChAdOx1-S (Group 5-7) - selected formulation of SCB-2019 or CoronaVac and CoronaVac (Group 8-10) - selected formulation of SCB-2019 or ChAdOx1) vs. a 2-dose ChAdOx1-S or CoronaVac series will be assessed.
Participants (N=400) will be randomly (2:1:1) distributed into 6 groups for Stage 2 and receive doses as follows:
Group 6: (N=50) Day 1 (boost) -ChAdOx1-S; Receives: Biological: ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford-AstraZeneca) |
| Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 7 | Experimental | For Stage 2, immunogenicity of heterologous booster vaccination schedule (ChAdOx1-S (Group 5-7) - selected formulation of SCB-2019 or CoronaVac and CoronaVac (Group 8-10) - selected formulation of SCB-2019 or ChAdOx1) vs. a 2-dose ChAdOx1-S or CoronaVac series will be assessed.
Participants (N=400) will be randomly (2:1:1) distributed into 6 groups for Stage 2 and receive doses as follows:
Group 7: (N=50) Day 1 (boost) -CoronaVac; Receives: Biological: CoronaVac (Sinovac Biotech) |
| Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 8 | Experimental | For Stage 2, immunogenicity of heterologous booster vaccination schedule (ChAdOx1-S (Group 5-7) - selected formulation of SCB-2019 or CoronaVac and CoronaVac (Group 8-10) - selected formulation of SCB-2019 or ChAdOx1) vs. a 2-dose ChAdOx1-S or CoronaVac series will be assessed.
Participants (N=400) will be randomly (2:1:1) distributed into 6 groups for Stage 2 and receive doses as follows:
Group 8: (N=100) Day 1 (boost) -SCB-2019; Receives: Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover) |
| Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 9 | Experimental | For Stage 2, immunogenicity of heterologous booster vaccination schedule (ChAdOx1-S (Group 5-7) - selected formulation of SCB-2019 or CoronaVac and CoronaVac (Group 8-10) - selected formulation of SCB-2019 or ChAdOx1) vs. a 2-dose ChAdOx1-S or CoronaVac series will be assessed.
Participants (N=400) will be randomly (2:1:1) distributed into 6 groups for Stage 2 and receive doses as follows:
Group 9: (N=50) Day 1 (boost) - ChAdOx1-S; Receives: Biological: ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford-AstraZeneca) |
| Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 10 | Experimental | For Stage 2, immunogenicity of heterologous booster vaccination schedule (ChAdOx1-S (Group 5-7) - selected formulation of SCB-2019 or CoronaVac and CoronaVac (Group 8-10) - selected formulation of SCB-2019 or ChAdOx1) vs. a 2-dose ChAdOx1-S or CoronaVac series will be assessed.
Participants (N=400) will be randomly (2:1:1) distributed into 6 groups for Stage 2 and receive doses as follows:
Group 10: (N=50) Day 1 (boost) - CoronaVac. Receives: Biological: CoronaVac (Sinovac Biotech) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immunogenicity - Stage 1
Immunogenicity is defined as the ability of cells/tissues to provoke an immune response and is generally considered to be an undesirable physiological response, as measured by ELISA (homologous strain) and virus neutralization assay (homologous and heterologous strains).
Measured: Day 1
Immunogenicity - Stage 1
Immunogenicity is defined as the ability of cells/tissues to provoke an immune response and is generally considered to be an undesirable physiological response, as measured by ELISA (homologous strain) and virus neutralization assay (homologous and heterologous strains).
Measured: Day 15
Immunogenicity - Stage 1
Immunogenicity is defined as the ability of cells/tissues to provoke an immune response and is generally considered to be an undesirable physiological response, as measured by ELISA (homologous strain) and virus neutralization assay (homologous and heterologous strains).
Measured: Day 29
Immunogenicity - Stage 2
Immunogenicity is defined as the ability of cells/tissues to provoke an immune response and is generally considered to be an undesirable physiological response, as measured by ELISA (homologous strain) and virus neutralization assay (homologous and heterologous strains).
Measured: Day 1
Immunogenicity - Stage 2
Immunogenicity is defined as the ability of cells/tissues to provoke an immune response and is generally considered to be an undesirable physiological response, as measured by ELISA (homologous strain) and virus neutralization assay (homologous and heterologous strains).
Measured: Day 15
Immunogenicity - Stage 2
Immunogenicity is defined as the ability of cells/tissues to provoke an immune response and is generally considered to be an undesirable physiological response, as measured by ELISA (homologous strain) and virus neutralization assay (homologous and heterologous strains).
Measured: Day 180
Immunogenicity - Stage 2
Immunogenicity is defined as the ability of cells/tissues to provoke an immune response and is generally considered to be an undesirable physiological response, as measured by ELISA (homologous strain) and virus neutralization assay (homologous and heterologous strains).
Measured: Day 360
Secondary outcomes (2)
Reactogenicity
Frequencies and percentages of participants experiencing local reactions and systemic solicited AEs; unsolicited AEs; SAEs; MAAEs and AESIs, will be summarized by vaccine group along with 95% CIs CI by the Clopper-Pearson method.
Measured: During 7 days after study vaccination
Reactogenicity
Frequencies and percentages of participants experiencing local reactions and systemic solicited AEs; unsolicited AEs; SAEs; MAAEs and AESIs, will be summarized by vaccine group along with 95% CIs CI by the Clopper-Pearson method.
Measured: After 28 days after study vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2021
- Study start1 Dec 2021 (estimated)
- Primary completion1 Apr 2022 (estimated)
- Study completion1 Apr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Controlled, observer-blinded, Phase 2 Study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 520 participants (estimated)
Sponsor and investigators
- Lead sponsor
- D'Or Institute for Research and Education
- Sponsor type
- University, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation, Instituto Fernandes Figueira
- Responsible party
- Sponsor
- Investigators
- Sue Ann Clemens Costa Clemens, MD, PhD, Study director, Global Health - Oxford University Siena University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05087368
- Sponsor's protocol ID
- TP-SCB-2019-001
- Acronym
- TP-SCB-2019001
- Status last verified
- Oct 2021
- First submitted
- 11 Aug 2021
- Last updated
- 21 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36043184
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT05087368
- Acronym / sponsor ID
- TP-SCB-2019001 / TP-SCB-2019-001
- Conditions
- Covid19
- Keywords
- Covid19, Immunogenicity, Vaccines
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 520 participants (estimated)
- Lead sponsor
- D'Or Institute for Research and EducationUniversity, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation, Instituto Fernandes Figueira
- Study start
- 1 Dec 2021 (estimated)
- Primary completion
- 1 Apr 2022 (estimated)
- Study completion
- 1 Apr 2022 (estimated)
- First posted
- 21 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 10
- Model description
- Controlled, observer-blinded, Phase 2 Study
| Arm | Type | Receives |
|---|---|---|
| Stage 1 - Formulation-finding for SCB-2019 - Group 1 | Experimental | Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover)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; |
| Stage 1 - Formulation-finding for SCB-2019 - Group 2 | Experimental | Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover)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 2: (N=30) Day 1: SCB-2019 (9 μg) CpG 1018/alum; |
| Stage 1 - Formulation-finding for SCB-2019 - Group 3 | Experimental | Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover)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 3: (N=30) Day 1: SCB-2019 (30 μg) CpG 1018/alum; |
| Stage 1 - Formulation-finding for SCB-2019 - Group 4 | Experimental | Biological: ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford-AstraZeneca)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 4: (N=30) Day 1: ChAdOx1-S; |
| Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 5 | Experimental | Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover)For Stage 2, immunogenicity of heterologous booster vaccination schedule (ChAdOx1-S (Group 5-7) - selected formulation of SCB-2019 or CoronaVac and CoronaVac (Group 8-10) - selected formulation of SCB-2019 or ChAdOx1) vs. a 2-dose ChAdOx1-S or CoronaVac series will be assessed. Participants (N=400) will be randomly (2:1:1) distributed into 6 groups for Stage 2 and receive doses as follows: Group 5: (N=100) Day 1 (boost) -SCB-2019; |
| Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 6 | Experimental | Biological: ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford-AstraZeneca)For Stage 2, immunogenicity of heterologous booster vaccination schedule (ChAdOx1-S (Group 5-7) - selected formulation of SCB-2019 or CoronaVac and CoronaVac (Group 8-10) - selected formulation of SCB-2019 or ChAdOx1) vs. a 2-dose ChAdOx1-S or CoronaVac series will be assessed. Participants (N=400) will be randomly (2:1:1) distributed into 6 groups for Stage 2 and receive doses as follows: Group 6: (N=50) Day 1 (boost) -ChAdOx1-S; |
| Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 7 | Experimental | Biological: CoronaVac (Sinovac Biotech)For Stage 2, immunogenicity of heterologous booster vaccination schedule (ChAdOx1-S (Group 5-7) - selected formulation of SCB-2019 or CoronaVac and CoronaVac (Group 8-10) - selected formulation of SCB-2019 or ChAdOx1) vs. a 2-dose ChAdOx1-S or CoronaVac series will be assessed. Participants (N=400) will be randomly (2:1:1) distributed into 6 groups for Stage 2 and receive doses as follows: Group 7: (N=50) Day 1 (boost) -CoronaVac; |
| Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 8 | Experimental | Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover)For Stage 2, immunogenicity of heterologous booster vaccination schedule (ChAdOx1-S (Group 5-7) - selected formulation of SCB-2019 or CoronaVac and CoronaVac (Group 8-10) - selected formulation of SCB-2019 or ChAdOx1) vs. a 2-dose ChAdOx1-S or CoronaVac series will be assessed. Participants (N=400) will be randomly (2:1:1) distributed into 6 groups for Stage 2 and receive doses as follows: Group 8: (N=100) Day 1 (boost) -SCB-2019; |
| Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 9 | Experimental | Biological: ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford-AstraZeneca)For Stage 2, immunogenicity of heterologous booster vaccination schedule (ChAdOx1-S (Group 5-7) - selected formulation of SCB-2019 or CoronaVac and CoronaVac (Group 8-10) - selected formulation of SCB-2019 or ChAdOx1) vs. a 2-dose ChAdOx1-S or CoronaVac series will be assessed. Participants (N=400) will be randomly (2:1:1) distributed into 6 groups for Stage 2 and receive doses as follows: Group 9: (N=50) Day 1 (boost) - ChAdOx1-S; |
| Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 10 | Experimental | Biological: CoronaVac (Sinovac Biotech)For Stage 2, immunogenicity of heterologous booster vaccination schedule (ChAdOx1-S (Group 5-7) - selected formulation of SCB-2019 or CoronaVac and CoronaVac (Group 8-10) - selected formulation of SCB-2019 or ChAdOx1) vs. a 2-dose ChAdOx1-S or CoronaVac series will be assessed. Participants (N=400) will be randomly (2:1:1) distributed into 6 groups for Stage 2 and receive doses as follows: Group 10: (N=50) Day 1 (boost) - CoronaVac. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female ≥18 years of age.
- Individuals are willing and able to comply with study requirements, including all scheduled visits, vaccinations, laboratory tests, and other study procedures.
- Individuals are willing and able to give an informed consent, prior to screening.
- Individuals who:
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford-AstraZeneca)Heterologous and Homologous Vaccination Series with ChAdOx1-S or CoronaVac COVID-19 Vaccines and Various Formulations of Clover Adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine (SCB-2019) in Adults | Biological | Stage 1 - Formulation-finding for SCB-2019 - Group 4, Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 6, Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 9 |
| CoronaVac (Sinovac Biotech)Heterologous and Homologous Vaccination Series with ChAdOx1-S or CoronaVac COVID-19 Vaccines and Various Formulations of Clover Adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine (SCB-2019) in Adults | Biological | Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 10, Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 7 |
| Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover)Heterologous and Homologous Vaccination Series with ChAdOx1-S or CoronaVac COVID-19 Vaccines and Various Formulations of Clover Adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine (SCB-2019) in Adults | Biological | Stage 1 - Formulation-finding for SCB-2019 - Group 1, Stage 1 - Formulation-finding for SCB-2019 - Group 2, Stage 1 - Formulation-finding for SCB-2019 - Group 3, Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 5, Stage 2 - Homologous vs. Heterologous Booster Regimen - Group 8 |
Primary outcome
Immunogenicity - Stage 1
Time frame: Day 1
Immunogenicity is defined as the ability of cells/tissues to provoke an immune response and is generally considered to be an undesirable physiological response, as measured by ELISA (homologous strain) and virus neutralization assay (homologous and heterologous strains).
Immunogenicity - Stage 1
Time frame: Day 15
Immunogenicity is defined as the ability of cells/tissues to provoke an immune response and is generally considered to be an undesirable physiological response, as measured by ELISA (homologous strain) and virus neutralization assay (homologous and heterologous strains).
Immunogenicity - Stage 1
Time frame: Day 29
Immunogenicity is defined as the ability of cells/tissues to provoke an immune response and is generally considered to be an undesirable physiological response, as measured by ELISA (homologous strain) and virus neutralization assay (homologous and heterologous strains).
Immunogenicity - Stage 2
Time frame: Day 1
Immunogenicity is defined as the ability of cells/tissues to provoke an immune response and is generally considered to be an undesirable physiological response, as measured by ELISA (homologous strain) and virus neutralization assay (homologous and heterologous strains).
Immunogenicity - Stage 2
Time frame: Day 15
Immunogenicity is defined as the ability of cells/tissues to provoke an immune response and is generally considered to be an undesirable physiological response, as measured by ELISA (homologous strain) and virus neutralization assay (homologous and heterologous strains).
Immunogenicity - Stage 2
Time frame: Day 180
Immunogenicity is defined as the ability of cells/tissues to provoke an immune response and is generally considered to be an undesirable physiological response, as measured by ELISA (homologous strain) and virus neutralization assay (homologous and heterologous strains).
Immunogenicity - Stage 2
Time frame: Day 360
Immunogenicity is defined as the ability of cells/tissues to provoke an immune response and is generally considered to be an undesirable physiological response, as measured by ELISA (homologous strain) and virus neutralization assay (homologous and heterologous strains).
2 secondary outcomes
Reactogenicity
Time frame: During 7 days after study vaccination
Reactogenicity
Time frame: After 28 days after study vaccination
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2021.
- Derived from this study: PubMed 36043184Costa 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sue Ann Clemens Costa Clemens, MD, PhD study director
Global Health - Oxford University Siena University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford-AstraZeneca), CoronaVac (Sinovac Biotech) and Adjuvanted Recombinant SARS-CoV-2 TrimericS-protein Subunit Vaccine (SCB-2019 - Clover) in people with Covid19, run by D'Or Institute for Research and Education at 3 sites in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eveline Pipolo Milan, MD (+55 (84) 2226-0373, evepipolo@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immunogenicity - Stage 1 (time frame: Day 1). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05087368, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2021.