| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Prevention of COVID-19 caused by SARS-CoV-2 |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 |
| To demonstrate the efficacy of SARS-CoV-2 rS with Matrix-M1 adjuvant in the prevention of virologically confirmed (by polymerase chain reaction [PCR]) to SARS-CoV-2, symptomatic COVID-19, when given as a 2-dose vaccination regimen, as compared to placebo, in serologically negative (to SARS-CoV-2) adult participants. |
|
| E.2.2 | Secondary objectives of the trial |
To demonstrate efficacy of the study drug in prevention of virologically confirmed, symptomatic COVID-19, versus placebo, regardless of
serostatus at baseline.
To assess efficacy of the study drug on:
- SARS-CoV-2 seropositive participants requiring specific medical interventions.
- mild COVID-19 symptoms.
- occurrence of asymptomatic or undetected infections with SARSCoV-2.
In a subset of participants, evaluate the immunogenicity of study drug.
To evaluate safety in terms of:
- SAEs and MAAEs related to study vaccination during entire study.
- AESI, which encompasses PIMMCs and AESIs relevant to COVID-19 including possible vaccine-enhanced disease, at any time after the first dose.
- All MAAEs for 14 days after second vaccination and unsolicited AEs for 21 days after first and 28 days after second study vaccinations.
In a subset, to evaluate safety and reactogenicity in terms of solicited local and systemic AEs for 7 days after each vaccination. |
|
| 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 |
A licensed seasonal influenza co-administration sub-study will be conducted in the first 400 participants who meet the additional inclusion criteria for this study.
After being randomised to receive IM injections of SARS-CoV-2 rS with Matrix-M1 adjuvant or placebo, sub-study participants will receive a licensed seasonal influenza vaccine on Day 0 in the opposite deltoid. These participants will be part of the solicited AE safety subset analysis.
This sub-group will undergo the same safety and efficacy evaluations as the entire study population. In addition, the entire sub-study will have reactogenicity assessed. This group must not have had a current season licensed influenza vaccine and have no prior history of allergy or severe reaction to seasonal influenza vaccine. To assess the possible impact of the study vaccine on the immunogenicity of the influenza vaccine, this group will also have a hemagglutination inhibition assay (HAI) performed.
Objective: In a subset of adult participants, to evaluate the safety and immunogenicity of SARS-CoV-2 rS with Matrix-M1 adjuvant when co-administered with a licensed seasonal influenza vaccine. |
|
| E.3 | Principal inclusion criteria |
1. Adult males or females aged 18 to 84 years (inclusive) at screening.
2. Able and willing (in the investigator’s opinion) to comply with all study requirements.
3. Willing to allow the investigators to discuss the volunteer’s medical history with their General Practitioner and access all medical records when relevant to study procedures.
4. Willing and able to give informed consent prior to study enrolment.
5. Female participants of childbearing potential (defined as any female who has experienced menarche and who is NOT surgically sterile [i.e., hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea at least 12 consecutive months or > 1 documented plasma follicle-stimulating hormone level ≥ 40 mIU/mL]) must agree to be heterosexually inactive from at least 28 days prior to enrolment and through 3 months after the last study vaccination OR agree to consistently use any of the following methods of contraception from at least 28 days prior to enrolment and through 3 months after the last study vaccination:
a. Condoms (male or female)
b. Diaphragm with spermicide
c. Cervical cap with spermicide
d. Intrauterine device
e. Oral or patch contraceptives
f. Norplant®, Depo-Provera®, or other in country regulatory-approved contraceptive method that is designed to protect against pregnancy
g. Abstinence, as a form of contraception, is acceptable if in line with the participant’s lifestyle (Other approaches to abstinence are not acceptable)
NOTE: Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.
6. Room air oxygen saturation >95% at Screening/Day 0
Seasonal Influenza Vaccine Co-Administration Sub-Study Only
7. Participant should not have received a current season influenza vaccine, have no contraindication to the specific vaccine to be administered in the study, and no prior history of allergy or severe reaction to seasonal influenza vaccines. |
|
| E.4 | Principal exclusion criteria |
1. Participation in COVID-19 prophylactic drug trials for the duration of the study.
2. Future participation in SARS-CoV-2 serological surveys where
participants are informed of their serostatus for the duration of the
study.
3. Participation in research involving an investigational product
(drug/biologic/device) within 45 days prior to first study vaccination.
4. History of laboratory-confirmed (by PCR or serology to SARS-CoV-2)
COVID-19 infection at any time prior to randomisation.
5. Administration of immunoglobulins and/or any blood products within the 3 months preceding the planned administration of the study vaccine
candidate.
6. Any confirmed or suspected immunosuppressive or immunodeficient state; chronic administration (defined as more than 14 continuous days) of immunosuppressant medication within the past 3 months, except
topical steroids or short-term oral steroids (course lasting ≤ 14 days).
NOTE: An immunosuppressant dose of glucocorticoid is defined as a
systemic dose ≥ 10 mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted if other chronic disease conditions are not exclusionary. HIV-positive participants receiving highly active antiretroviral therapy and a history within 6 months of screening of viral load < 1000 copies/mL or CD4 count > 300 cells/mm3 would be eligible.
7. History of allergic disease or reactions likely to be exacerbated by any component of the study vaccines.
8. Any history of anaphylaxis to any prior vaccine.
9. Pregnancy, lactation or willingness/intention to become pregnant within 3 months following the last study vaccination.
10. Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ, at the discretion of the investigator).
11. Bleeding disorder (e.g., factor deficiency, coagulopathy or platelet
disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture.
12. Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e., warfarin) or novel oral anticoagulants/anti-platelet
agents. (NOTE: The use of ≤ 325 mg of aspirin per day as prophylaxis is
permitted)
13. Suspected or known current alcohol or drug dependency.
14. Study team member or first-degree relative of any study team
member (inclusive of sponsor, contract research organisation (CRO), and site personnel involved in the study).
15. Participants who are having any current workup of undiagnosed
illness within the last 8 weeks that is either participant-reported or has
been clinician-assessed, which could lead to a new condition or
diagnosis.
16. Received any live vaccine within 4 weeks or any vaccine (excluding
influenza) within 2 weeks prior to first study vaccination or any licensed influenza vaccine within 1 week prior to first study vaccination or plans to receive any vaccine from these time periods until 28 days after second study vaccination. NOTE: In addition, a licensed seasonal influenza vaccine may be given 7 days after dose 1 and dose 2 but should not be given within 7 days of dose 2.
17. Have clinically significant chronic cardiovascular, endocrine,
gastrointestinal, hepatic (including hepatitis B and C), renal,
neurological, respiratory, psychiatric or other medical disorders not
excluded by other exclusion criteria, that are assessed by the investigator as being clinically unstable within the prior 4 weeks as evidenced by:
a. Hospitalisation for the condition, including day surgical interventions.
b. New significant organ function deterioration.
c. Needing addition of new treatments or major dose adjustments of current treatments (mild or moderate well-controlled comorbidities are allowed).
18. History of chronic neurological disorders that have required prior
specialist physician review for diagnosis and management (multiple sclerosis, dementia, transient ischemic attacks, Parkinson's disease,
degenerative neurological conditions and neuropathy) or a history of stroke or previous neurological disorder within 12 months with residual
symptoms. Participants with a history of migraine or chronic headaches or nerve root compression that have been stable on treatment for the
last 4 weeks are not excluded.
19. Any autoimmune disease/condition (iatrogenic or congenital) in Table 9-3 or being treated with a biologic therapy.
20. Any other significant disease, disorder or finding that, in the opinion of the investigator, may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study, or impair interpretation of the study data.
21. Participant requires the use of continuous oxygen therapy or any
oxygen therapy while awake or is anticipated to require daytime oxygen therapy during the course of the study. NOTE: Nocturnal oxygen use only is acceptable for study inclusion. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
First occurrence of virologically confirmed (by PCR to SARS-CoV-2), symptomatic mild, moderate or severe COVID-19 with onset at least 7 days after second study vaccination (e.g., Day 28) in serologically negative (to SARS-CoV-2) adult participants at baseline until the endpoint-driven efficacy analysis is triggered by the occurrence of a prespecified number of blinded endpoints.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| This will be an event-driven study for the assessment of vaccine efficacy (VE) and will end when a sufficient number of events have been observed, yet all participants will be followed for the entire study duration for safety endpoints. |
|
| E.5.2 | Secondary end point(s) |
The key secondary endpoint is:
- First occurrence of virologically confirmed (by PCR to SARS-CoV-2), symptomatic moderate or severe COVID-19 with onset at least 7 days after second study vaccination (e.g., Day 28) in serologically negative
(to SARS-CoV-2) adult participants at baseline until the endpoint-driven efficacy analysis is triggered by the occurrence of a prespecified number of blinded endpoints.
The other secondary endpoints are:
− First occurrence of virologically confirmed (by PCR to SARS-CoV-2), symptomatic mild, moderate or severe COVID-19, with onset at least 7 days after second study vaccination (e.g., Day 28) in adult participants regardless of their serostatus at baseline.
− First occurrence of laboratory-confirmed (by PCR or nucleocapsid (N)protein serology to SARS-CoV-2) symptomatic or asymptomatic COVID19 with onset at least 7 days after second study vaccination (e.g., Day 28) in adult participants regardless of their serostatus at baseline.
− First occurrence of COVID-19 requiring hospitalisation, intensive care unit (ICU) admission or mechanical ventilation linked to any virologically confirmed (by PCR to SARS-CoV-2) COVID-19 with onset at least 7 days after second study vaccination (e.g., Day 28) in adult participants regardless of their serostatus at baseline.
− First occurrence of virologically confirmed (by PCR to SARS-CoV-2), symptomatic mild COVID-19 (with no progression to moderate or severe COVID-19 during the course of the COVID-19 episode) with onset at
least 7 days after second study vaccination (e.g., Day 28) in adult participants, regardless of their serostatus at baseline.
− Analysis of antibodies binding to the SARS-CoV-2 spike (S) protein by enzyme-linked immunosorbent assay (ELISA) at Day 0 (baseline) and Day 35 (14 days after second study vaccination).
− The occurrence and relationship to study vaccination of SAEs and MAAEs related to study vaccination (in all adult participants) during the entire study period.
− The occurrence and relationship to study vaccination of AESIs and PIMMCs (in all adult participants) during the entire study period.
− The occurrence and severity of reactogenicity in terms of solicited local and systemic AEs (in sub-study participants) for 7 days after each study vaccination.
− The occurrence, severity, and relationship to study vaccination of all MAAEs for 14 days after second vaccination and unsolicited AEs (in all adult participants) for 21 days after first study vaccination and 28 days after second study vaccination. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| This will be an event-driven study for the assessment of vaccine efficacy (VE) and will end when a sufficient number of events have been observed, yet all participants will be followed for the entire study duration for safety endpoints. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| 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) | No |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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 | 28 |
| 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 | 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
|
| The end of the study is defined as the date on which the last participant completes the last study visit (including the EOS visit and any additional long-term follow-up). |
|
| 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 | 1 |
| 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 | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
