E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The aim is to study primarily effectiveness as well as safety of citizens being vaccinated with one of the SARS-CoV2 vaccines being applied in the Danish COVID-19 vaccine programme. Whereas ongoing phase III trials are reporting vaccine efficacy in defined study populations, the effectiveness of these vaccines – and in particular the durability hereof - once introduced into the general population is presently unknown, and the focus of intense research and public health interest.
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Health Care [N] - Environment and Public Health [N06] |
MedDRA Classification |
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 primary objective of the study is to assess effectiveness of citizens being vaccinated with one of SARS-CoV2 vaccines the government has purchased, and the Danish Medicines Agency has approved for use in Denmark. The study will compare and predict the durability of the minimal protective titre afforded by each of the vaccines against COVID-19 through conducting comprehensive high-throughput SARS-CoV-2 antibody analyses and in-depth characterization of the vaccine-induced cellular immune response |
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E.2.2 | Secondary objectives of the trial |
In relation to effectiveness, the following outcome will be compared between vaccine groups: • Breakthrough infections throughout the 24 month follow-up period. • A series of more detailed immunological assessment in subgroups of participants of markers of cellular immunity (see appendix 3)
In relation to safety, the following outcome will be compared between vaccine groups: • Participants with local and systemic reactions to vaccination • Grade 3 and 4 adverse events and serious adverse events. This will be ascertained and reported by study-affiliated staff. Primary safety outcomes are any grade 3 or 4 (i.e. serious) events observed within the first three months after the initial vaccination. • Grade 1 and 2 events. This will be ascertained by study-affiliated staff as present on the specific day of Visit 2 and Visit 3.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Appendix 3 to the protocol: Under separate participant informed consent, a cohort will be established including 250 patients (100 healthy and 150 high-risk individuals) from each vaccine group. Live cells (PBMCs) and PAX tubes (for transcriptomic analysis) will be collected for the participants in this cohort. Several work packages or sub-studies will be embedded within this cohort addressing basic and translational research questions requiring additional sampling of biological material as described below. Work package 1 (WP1): Immunogenicity: Biobanking of live cells (liquid nitrogen) Work package 2 (WP2): Characterization of polyclonal antibody responses to SARS-CoV-2 variants Work package 3 (WP3): Characterization of adaptive immune response in individuals with breakthrough infections Work package 4 (WP4): Cellular Immunity: Longitudinal immunoprofiling of vaccine responses in SARS CoV-2 vaccinated individuals
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E.3 | Principal inclusion criteria |
1. Written informed consent obtained before any trial related procedures are performed 2. Male or female eligible for SARS-CoV-2 immunization (as defined by SST in the national vaccination plan) 3. The subject must be willing and able to comply with trial protocol (re-visits and biological samples)
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E.4 | Principal exclusion criteria |
1. Male and female under the age of 18 2. Any subgroup of individuals for which the vaccines are contra-indicated 3. Previous SARS-CoV-2 vaccination
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome is the minimal protective neutralising antibody titre (MPNAT); i.e. the minimum level of neutralising antibodies sufficient to protect the person from becoming infected.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
MPNAT will be measured via profiling of antibodies against SARS-CoV-2 Spike epitopes performed at each visit until month 24.
The exact value of the MPNAT is currently not precisely defined, but is expected to be documented within short periods of time based on analyses across the ongoing phase III trials, associating titre levels with risk of breakthrough infection in the actively vaccinated group.
As the exact value of the MPNAT remains to be determined, and until that time point has arisen, a priori (i.e. while remaining blinded to the actually obtained data) of the actually defined cut-offs in neutralising titres that reasonable can serve as proxy for the MPNAT will be recommended by an expert advisory panel, and endorsed by the study leadership
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | No |
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
| Yes |
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 | 50 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |