A phase 3, randomised, observer-blinded, placebo-controlled trial to evaluate the efficacy and safety of a Sars-Cov-2 recombinant spike protein nanoparticle vaccine (Sars-Cov-2 RS) with Matrix-M1TN adjuvant in adult participants 18-84 years of age in the United Kingdom.
Aim of the study:
The purpose of this study is to evaluate the efficacy, safety, and immunogenicity of SARS-CoV-2 rS with Matrix-M1 adjuvant in adults 18-84 years of age (inclusive). The study will be conducted at anticipated high COVID-19 transmission areas in the United Kingdom (UK). The information provided in this study will inform progression of the study vaccine, to determine efficacy of the study vaccine to prevent COVID-19 in the general population, in participants regardless of serostatus, in participants who have required medical intervention, and in participants with mild or asymptomatic infections. The study will determine the safety of the study vaccine to use in the general population and to ensure that it elicits a robust immune response.
Inclusion and exclusion criteria:
- Adult males or females aged 18 to 84 years (inclusive) at screening.
- Able and willing (in the investigator’s opinion) to comply with all study requirements.
- 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.
- Willing and able to give informed consent prior to study enrolment.
- Female participants of childbearing potential 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.
- Room air oxygen saturation > 95% at Screening/Day 0.
- Participation in COVID-19 prophylactic drug trials for the duration of the study.
- Future participation in SARS-CoV-2 serological surveys where participants are informed of their serostatus for the duration of the study.
- Participation in research involving an investigational product (drug/biologic/device) within 45 days prior to first study vaccination.
- History of laboratory-confirmed (by PCR or serology to SARS-CoV-2) COVID-19 infection at any time prior to randomisation.
- Administration of immunoglobulins and/or any blood products within the 3 months preceding the planned administration of the study vaccine candidate.
- 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).
- History of allergic disease or reactions likely to be exacerbated by any component of the study vaccines.
- Any history of anaphylaxis to any prior vaccine.
- Pregnancy, lactation, or willingness/intention to become pregnant within 3 months following the last study vaccination.
- 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).
- Bleeding disorder (e.g., factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture.
- Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e., warfarin) or novel oral anticoagulants/anti-platelet agents.
- Suspected or known current alcohol or drug dependency.
- 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).
- 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.
- 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.
- 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:
- Hospitalisation for the condition, including day surgical interventions.
- New significant organ function deterioration.
- Needing addition of new treatments or major dose adjustments of current treatments (mild or moderate well-controlled comorbidities are allowed).
- History of chronic neurological disorders that have required prior specialist physician review for diagnosis and management (such as 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.
- Any autoimmune disease/condition (iatrogenic or congenital) listed in Table 9-3 or being treated with a biologic therapy.
- 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.
- 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.
What participating in the study involves?: If you decide to take part, you will be in the study for approximately 1 year after your second study vaccination in the First Vaccination Period (including screening). You will have to visit the study site (i.e., clinic) at least 6 times. All visits will involve only day visits to the study site. You may have to attend unscheduled (extra) visits if you develop COVID-19-like symptoms in order to see if you have COVID-19.
Key Tests and Assessments:
- Demographics and Medical History
- Physical Examination and Vital Signs
- Pregnancy Tests
- Nose/Throat Swab testing for SARS-CoV-2
- Blood tests
- COVID-19 Symptom Diary (if you develop symptoms)
- Self Nose/Throat Swab testing for SARS-CoV-2 (if you develop symptoms)
- Health Checks and Medication Review
Results: UK Novavax COVID-19 vaccine trial. We are pleased to report that the first results from this trial will be published in the New England Journal of Medicine and will become available at their website. https://www.nejm.org/doi/full/10.1056/NEJMoa2107659?query=featured_home
Here is a summary of these results:
Background: the earlier Novavax (NVX) Phase 1/2 trials had indicated that the NVX vaccine was safe and showed a good immune response against the Covid-19 virus. The UK Phase 3 trial was designed to show if the vaccine was also safe when given to large numbers of people and could actually protect them (provide “efficacy”) against Covid-19.
Trial results: In total 15,187 participants were recruited. 27% were older than 65 years. Half of the participants (7,569) were randomised to receive the NVX vaccine, and the other half (7,570) to receive the placebo (normal saline water). 400 participants were also recruited into an “Influenza Sub-study” to look at the results when the NVX vaccine was given at the same time as an influenza vaccine. The results of this will be published separately.
Safety: 2,310 participants were asked to complete an electronic diary for 7 days after each vaccine and to record any symptoms. Overall, those who received the NVX vaccine reported more injection site symptoms than those who received the placebo: around 58% vs. 18% after the first dose and 80% vs. 16% after the 2nd dose. These were mainly tenderness and pain, lasting around 2-3 days after each dose. Headache, muscle pain and fatigue were also reported (more commonly after the 2nd dose: each at around 40%) and again were short-lived (average of 2 days). Across the whole study “serious” adverse events were very rare and were equal in both the vaccine and the saline placebo groups (0.6%). There were no serious allergic reactions.
Efficacy: There were 10 cases of symptomatic Covid-19 from 7 or more days after the 2nd dose of the Novavax vaccine (none required hospitalisation), as compared with 96 cases after the placebo (89.7% efficacy). Most of the cases (66) were caused by the Kent variant (B.1.1.7, now called the alpha variant), and the efficacy was 86.3% against this variant. The vaccine was equally effective in all age groups, including those ³65 years old, and in those with a range of other health problems.
In summary, two doses of the NVX vaccine provides around 90% protection against symptomatic Covid-19 and appears to be safe. We look forward to reporting more results to you after a longer period of follow up. We are highly appreciative of the ongoing contributions of all our participants in this trial.