| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| SARS-CoV-2-mediated COVID-19 |
|
| E.1.1.1 | Medical condition in easily understood language |
| COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 23.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10084465 |
| E.1.2 | Term | COVID-19 vaccination |
| E.1.2 | System Organ Class | 100000004865 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
1. Primary Efficacy Objective: Vaccine Efficacy Against RT-PCR-Confirmed COVID-19 of Any Severity: To demonstrate the efficacy of CpG 1018/Alum-adjuvanted SCB-2019 vaccine for the prevention of any RT-PCR-confirmed COVID-19 of any severity in subjects without evidence of prior SARS-CoV-2 infection.
2. Primary Safety and Reactogenicity Objective: To assess the safety and reactogenicity of CpG 1018/Alum-adjuvanted SCB-2019 vaccine compared to placebo.
3. Primary Immunogenicity Objective: To demonstrate that SCB-2019 vaccine when given as a booster dose (full dose) elicits an immune response that is noninferior to the immune response when given as primary 2-dose series, as measured by virus neutralization assay at 14 days after third (booster dose) or second (primary 2-dose series) vaccination in subjects without evidence of prior SARS-CoV-2 infection. |
|
| E.2.2 | Secondary objectives of the trial |
Efficacy Against: Any RT-PCR Confirmed Moderate-to-Severe COVID-19;
Any Laboratory-Confirmed SARS-CoV-2 Infection;
Any RT-PCR-Confirmed Severe COVID-19; Any Lab-Confirmed Asymptomatic SARS-CoV-2 Infection; BOD; Any RT-PCR-Confirmed COVID-19 of Any Severity Associated with Hospitalization; SARS-CoV-2 VOC
Efficacy by Evidence of Prior SARS-CoV-2 Infection and Risk of Severe COVID-19
Efficacy After the First Dose
Assess the immunogenicity (IG) of CpG 1018/Alum-adjuvanted SCB 2019 vaccine in Phase 2 adult subjects (AS) and adolescents (AD)
Demonstrate that SCB-2019 vaccine when given to AD (12-17 y) elicits an immune response (IR) that is noninferior to the IR in young adults (18-25 y)
Assess the IG of CpG 1018/Alum-adjuvanted SCB 2019 vaccine when given as a booster dose
Assess the IR against Trimer Tag domain of SCB 2019 in Phase 2 AS and ADs
Assess the safety and reactogenicity of CpG 1018/Alum-adjuvanted SCB-2019 vaccine administered as a booster dose (full and half dose) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or females ≥12 years of age, inclusive.
2. Participants who are willing and able to comply with study requirements, including all scheduled visits, vaccinations, laboratory tests, the electronic completion of the COVID-19 ePRO and other study procedures.
3. Healthy adult or adolescent subjects or adult or adolescent subjects with pre-existing medical conditions who are in stable condition.
4. 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.
Note: The first 200 individuals enrolled in the Phase 2 part of the study should be healthy subjects 18 to 64 years or age without comorbidities associated with a high risk of severe COVID-19.
5. Female subjects who are WOCBP are eligible to participate in the study if not pregnant, not breastfeeding, and at least 1 of the following criteria apply:
• WOCBP must have a negative urine pregnancy test prior to each 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 second vaccination.
6. Male subjects must agree to employ acceptable contraception from the day of first dose of the study vaccine/placebo until 6 months after the last dose of the study vaccine/placebo and also refrain from donating sperm during this period.
7. Individuals (or their legally acceptable representative based on local regulations) willing and able to give an informed consent, prior to screening. For adolescent subjects: informed assent signed by adolescents and informed consent signed by the parent(s) or legally acceptable representative(s) as per local requirements.
8. Applicable for HIV-positive individuals only:
HIV positive individuals can participate in the study only if,
- They are medically stable at screening, as determined by the investigator, and free of opportunistic infections in the 1 year prior to first study vaccination, and
- They have an HIV-1 viral load <1000 copies/mL within 45 days of randomization in the study, and
- They are receiving highly active antiretroviral therapy (HAART) for at least 3 months before screening. Changes in antiretroviral dosage within 3 months of entering the study are allowed, as are exchanges in pharmacological formulations.
Note 1: No HIV screening is required except participants in South Africa due to the high prevalence of HIV, prior to study enrollment, individuals without recent HIV testing (within previous 6 months), should undergo screening for HIV using an approved method, as per site standard medical practice to determine if they can participate in the study.
Note 2: Inclusion criteria should also be used to determine whether the placebo recipient is eligible to receive SCB-2019 or SCB-2019 recipient is eligible to participate in booster cohort. Additional inclusion criterion for SCB-2019 recipients from Phase 3 part of the study to participate in the booster cohort:
9. Participants who have received 2 prior doses of SCB-2019 vaccine with at least 4 months between the second vaccination and the booster dose. |
|
| E.4 | Principal exclusion criteria |
1. Individuals with laboratory-confirmed SARS-CoV-2 infection (e.g., a positive RT-PCR or Rapid COVID-19 antigen test) at screening or within 14 days prior to enrollment.
2. Individuals with behavioral or cognitive impairment (including drug and alcohol abuse) in the opinion of the Investigator.
3. Individuals with any progressive or severe neurologic disorder, seizure disorder, or history of Guillian-Barré syndrome.
4. Individuals who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, e.g., for cancer or an autoimmune disease, or planned receipt during the study period. If a short-term course of systemic corticosteroids have been administered for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 30 days before the first study vaccination. A unique dose of systemic steroids on a single day would be allowed, as well as inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
5. Individuals who are pregnant, or breastfeeding, or planning to become pregnant during the study period.
6. Individuals who have a history of severe adverse reaction associated with a vaccine or severe allergic reaction (e.g., anaphylaxis) to any component of the study vaccine (SCB-2019, CpG 1018 Adjuvant and Aluminum hydroxide/SCB-2019 components as outlined in the latest IB).
7. Individuals who have a history of malignancy within 1 year before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix which have been cured, or other malignancies with minimal risk of recurrence).
8. Individuals who have received any other investigational product within 30 days prior to Day 1 or intent to participate in another clinical study at any time during the conduct of this study.
9. Individuals who have received previous vaccination with any coronavirus vaccine.
10. Individuals who have received any other licensed vaccines within 14 days prior to enrollment in this study or who are planning to receive any vaccine up to 14 days after the second vaccination.
11. Individuals with known bleeding disorder that would, in the opinion of the investigator, contraindicate intramuscular injection.
12. Individuals who received any blood/plasma products or immunoglobulins within 60 days prior to Day 1 or plan to receive it during the study period.
13. Individuals with any condition that, in the opinion of the Investigator, may increase the risk of study participation or interfere with the assessment of the primary study objectives
14. Individuals with fever >37.8°C (irrespective of method), or any acute illness at baseline (Day 1) or within 3 days of randomization. Participants meeting this criterion may be rescheduled within the relevant window. A febrile participant with minor illness can be enrolled at the discretion of the investigator.
Note: Exclusion criteria should also be used to determine whether the placebo subject is eligible to receive SCB-2019 or SCB-2019 recipient is eligible to participate in booster cohort. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary efficacy endpoint:
- First occurrence of any RT-PCR-confirmed COVID-19 of any severity with onset at least 14 days after the second study vaccination in subjects without evidence of prior SARS-CoV-2 infection.
Primary safety and reactogenicity endpoints:
- Local and systemic solicited AEs (Days 1-7 after vaccination; Phase 2 subjects only)
- Unsolicited AEs (Days 1-43; Phase 2 subjects only)
- SAEs, AEs leading to early termination from the study, MAAEs, and AESIs during the entire study period (in all subjects).
Primary Immunogenicity Objective:
SARS-CoV-2–neutralization titers after booster dose (Day 15A) and primary vaccination series (Day 36) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
For efficacy endpoint: From 14 days after the second study vaccination until the end of efficacy surveillance
For safety and reactogenecity endpoints:
- For local and systemic solicited AEs: 7 days after each vaccination
- For unsolicited AEs: from Day 1 to Day 43
- For SAEs, AEs leading to early termination from the study: during the entire study period
Primary Immunogenicity Objective: Day 36 (15 days after primary vaccination series) and Day 15A (15 days after booster dose) |
|
| E.5.2 | Secondary end point(s) |
The following endpoints will be assessed in subjects without evidence of prior SARS-CoV-2 infection, from 14 days after the second vaccination:
- First occurrence of RT-PCR confirmed moderate-to-severe COVID 19
- First occurrence of RT-PCR confirmed severe COVID 19
- Occurrence of any SARS-CoV-2 infection
- Occurrence of laboratory-confirmed asymptomatic SARS-CoV-2 infection
- Borden of disease (occurrence of any SARS-CoV-2 infection, any RT PCR COVID-19 and any RT-PCR-confirmed severe COVID-19)
- First occurrence of RT-PCR confirmed COVID 19 of any severity, associated with hospitalization
- First occurrence of RT-PCR confirmed COVID 19 in subjects with high risk of severe COVID-19
- First occurrence of RT-PCR-confirmed COVID-19 of any severity, caused by SARS-CoV-2 variants of concern
The following endpoints will be assessed in subjects with evidence of prior SARS-CoV-2 infection, from 14 days after the second vaccination:
- First occurrence of RT-PCR confirmed COVID 19 of any severity
- First occurrence of RT-PCR confirmed moderate-to-severe COVID 19
- First occurrence of RT-PCR confirmed severe COVID 19
- Occurrence of any SARS-CoV-2 infection
- Occurrence of laboratory-confirmed asymptomatic SARS-CoV-2 infection
- First occurrence of RT-PCR confirmed COVID 19 of any severity, associated with hospitalization
The following endpoints will be assessed in subjects without evidence of prior SARS-CoV-2 infection, from 14 days after the first vaccination:
- First occurrence of RT-PCR confirmed COVID 19 of any severity
- First occurrence of RT-PCR confirmed moderate-to-severe COVID 19
- First occurrence of RT-PCR confirmed severe COVID 19
- Occurrence of any SARS-CoV-2 infection
- Occurrence of laboratory-confirmed asymptomatic SARS-CoV-2 infection
- First occurrence of RT-PCR confirmed COVID 19 of any severity, associated with hospitalization
Secondary immunigenicity endpoints:
- VNA with wild-type strain, VNA with pseudovirus (in adults only), SCB-2019 binding antibody ELISA, and ACE2-competitive ELISA (in adults only): GMTs, GMFRs (post/pre-vaccination), proportion of subjects with seroconversion, and proportion of subjects with antibody titer above a pre-specified threshold
Secondary safety endpoint:
- Trimer-Tag binding antibody as measured by ELISA assay
- Local and systemic solicited AEs reported within 7 days after booster dose of study vaccine (subset);
- Unsolicited AEs reported from Visit 1A (Day 1A) through Safety Call (Day 21A) in the booster cohort (subset). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy Endpoints: from 14 days after the second vaccination up to the end of efficacy surveillance period, or from 14 days after the first vaccination up to the end of efficacy surveillance period
For Immunogenicity and safety endpoints: Days 1, 22, 35, 205 and 389 (primary vaccination series) and Days 1, 15 and 389 (booster series) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 9 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Belgium |
| Brazil |
| Colombia |
| Philippines |
| South Africa |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
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