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) |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 |
|
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 |
|
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 |
To determine the need for, optimal timing of, and immunogenicity of administering a 4th homologous vaccination dose against SARS-CoV-2 in the general population (18+ years) already vaccinated with the BNT162b2 vaccine. |
|
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 4th dose vaccine in comparison to prior to 4th 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 3rd dose of initial vaccination and 4th 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 4th dose vaccine • To explore primary and secondary endpoints stratified by incident infection pre-4th dose vaccine or by any modification of vaccine epitope.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adults aged 18 years or above at baseline • Be at least three but no more than 6 months (+/- 4 weeks) from the date of 3rd dose of BNT162b2 vaccine at the time of consent • Have received three homologous doses as primary vaccination against SARS-CoV-2 with BNT162b2 vaccine (vaccination status should be documented). • Written informed consent from the subject has been obtained.
|
|
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 • 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 sponsor or principal investigator or employed by the sponsor or principal investigator • Where a subject’s primary vaccination and third dose vaccination was not with the BNT162b2 mRNA vaccine • Any contraindication to the vaccines in the trial as per the Summary of Medicinal Product Characteristics, SmPC) or the Investigator’s Brochure, if appropriate. • Use of drugs with significant interaction with the investigational product • Subjects who are pregnant and who are planning to become pregnant • Nursing mothers • Unwillingness to use highly effective contraceptive methods.
|
|
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 4th dose booster vaccine in those with anti-RBD antibody titre of ≤500 IU/mL immediately before 4th dose booster vaccination or a 2-fold increase in anti-RBD antibody titre at day 14 following 4th dose vaccination in those with anti-RBD titre of ≥500 IU/mL immediately before 4th dose booster vaccination, as measured by quantitative immunoassay targeting the anti-RBD antibody. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
14 days after 3rd dose vaccine |
|
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 4th dose vaccination at each specific timepoint that achieve a 2-fold increase in RBD antibody titre 14 days after the 4th dose vaccine • The proportion of subjects who receive 4th dose vaccination at each specific timepoint that achieve an anti-RBD antibody titre ≥500 IU/mL 14 days after the 4th dose vaccine • Rate of 2-fold RBD antibody titre increase following 4th dose vaccination measured by quantitative immunoassay targeting the spike 1 (S1) and nucleocapsid (NC) antibodies at 14 days after 4th dose vaccine as compared to immediately before vaccination • Analysis stratified by incident pre-4th dose SARS-CoV-2 infections and any modification of vaccine epitope
Safety/tolerability: • Solicited AEs for 7 days after 4th dose • Unsolicited/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 4th dose or subject completes the study, whichever occurs first.
Laboratory: • T-cell activation as measured by a whole blood dq-TACT assay before and 14 days after 4th 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
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
7 and 14 days after 3rd dose vaccine |
|
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) |
|
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.8.5 | 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 |
Sweden |
Netherlands |
Spain |
Switzerland |
Germany |
Belgium |
Denmark |
Ireland |
Norway |
|
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 | 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 |