E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Acute Respiratory Syndrome Coronavirus 19 (COVID-19/SARS-CoV-2) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10084457 |
E.1.2 | Term | COVID-19 immunisation |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084462 |
E.1.2 | Term | SARS-CoV-2 vaccination |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
The overarching objective is to evaluate anti-SARS-CoV-2 immune responses to different booster strategies in individuals already fully vaccinated against SARS-CoV-2. Specifically, this subprotocol will determine the need for, optimal timing of and immunogenicity of administering a 3rd homologous vaccination dose against SARS-CoV-2 in the general population (18+ years) who have already vaccinated with two doses of the BNT162b2 vaccine. |
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E.2.2 | Secondary objectives of the trial |
• To determine the change in cellular immune response measured by a direct from blood qPCR based T-cell activation (dq-TACT) assay at 14 days after 3rd dose vaccine in comparison to prior to 3rd dose vaccination. • To correlate humoral immune response, cellular immune responses and viral neutralising capacity against wild type SARS-CoV-2 • To determine the durability of humoral and cellular immune responses after initial and third dose vaccination • To determine rates of, and maximum disease severity associated with confirmed SARS-CoV-2 infections occurring after enrolment in study participants before and after 3rd dose vaccine
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Adults aged 18 years or above at baseline -Be no more than 9 months (+/- 6 weeks) from the date of second dose of BNT162b2 vaccine at the time of consent -Have received two homologous doses as primary vaccination against SARS CoV-2 with BNT162b2 vaccine (vaccination status should be documented). -No contra-indication against any of the vaccine products in the trial. -Written informed consent from the subject has been obtained. |
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E.4 | Principal exclusion criteria |
-Unable to provide written, informed consent -Participation in any other interventional trials -People who have already received a booster vaccination -Any significant or uncontrolled disease posing a risk with vaccination as judged by the investigator (including recent, confirmed positive SARS-CoV-2 test within the previous three weeks) - Any significant medical condition that in the opinion of the investigator would necessitate booster vaccination against SARS-CoV-2 within the trial timelines - Any kind of dependency on the principal investigator or employed by the sponsor or principal investigator -Where a subject received primary vaccination not with two doses of the BNT162b2 mRNA vaccine or the primary vaccination was with two different vaccine products as 1st and 2nd vaccination doses (heterologous vaccination scheme) -Any contraindication to the vaccines in the trial at the moment of randomization as per the Summary of Medicinal Product Characteristics, SmPC) or the Investigator’s Brochure, if appropriate. A list of contraindications (including prior anaphylaxis to BNT162b2) are listed in Annex A. -Use of drugs with significant interaction with the investigational product -Subjects who are pregnant -Unwillingness to use highly effective contraceptive methods. The following contraceptive methods with a Pearl Index lower than 1% are regarded as highly-effective: o Oral hormonal contraception o Dermal hormonal contraception o Vaginal hormonal contraception (NuvaRing®) o Contraceptive plaster o Long-acting injectable contraceptives o Implants that release progesterone (Implanon®) o Tubal ligation (female sterilisation) o Intrauterine devices that release hormones (hormone spiral) o Double barrier methods |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint comprises a composite endpoint of either an increase in anti-RBD antibody titre to ≥500 IU/mL at day 14 post 3rd dose booster vaccine in those with anti-RBD antibody titre of ≤500 IU/mL immediately before 3rd dose booster vaccination or a 2-fold increase in anti-RBD antibody titre at day 14 following 3rd dose vaccination in those with anti-RBD titre of ≥500 IU/mL immediately before 3rd dose booster vaccination, as measured by quantitative immunoassay targeting the anti-RBD antibody. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
14 days after 3rd dose vaccine |
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E.5.2 | Secondary end point(s) |
• The proportion of subjects reporting positive tests (PCR and/or antigen tests) for SARS-CoV-2 at each reporting time point after enrolment • The proportion of subjects who receive 3rd dose vaccination at each specific timepoint that achieve a 2-fold increase in RBD antibody titre 14 days after the 3rd dose vaccine • The proportion of subjects who receive 3rd dose vaccination at each specific timepoint that achieve an anti-RBD antibody titre ≥500 IU/mL 14 days after the 3rd dose vaccine • Rate of 2-fold RBD antibody titre increase following 3rd dose vaccination measured by quantitative immunoassay targeting the spike 1 (S1) and nucleocapsid (NC) antibodies at 14 days after 3rd dose vaccine as compared to immediately before vaccination
Safety/tolerability: • Unsolicited AEs for 14 days after 3rd dose • Solicited AEs for 7 days after 3rd dose • Spontaneous AEs until the end of trial • Rate of serious adverse events (SAEs) Grade ≥3 according to the National Cancer Institute Common Toxicity Criteria until up to three months after 3rd dose
Laboratory: • T-cell activation as measured by a whole blood dq-TACT assay before and 14 days after 3rd dose vaccine • Neutralising activity against SARS-CoV-2 wild-type and variants of concern as measured by a standardised viral neutralisation assay (sub-group analysis)
Exploratory endpoints: • Detailed immunophenotyping of immune responses, including metabolomics, proteomics and transcriptomics where relevant (sub-group analysis) • Whole genome sequencing of isolated SARS-CoV-2 viral strains detected in breakthrough infections • Haemagglutination assay as a surrogate of neutralising capacity
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
7 and 14 days after 3rd dose vaccine |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Control group offered 3rd dose vaccine at the end of the study(19 months after initial vaccination) |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
Denmark |
Germany |
Ireland |
Netherlands |
Norway |
Spain |
Sweden |
Switzerland |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |