Trial ISRCTN73765130
Publication Munro A, Lancet, 2021
Dates: 2021-06-01 to 2021-06-30
Funding: Mixed (UK Government through the National Institute for Health Research (NIHR) and the Vaccine Taskforce; NVX, VLA, Ad26, and CVn were supplied by the manufacturers, without charge.)
Conflict of interest: Yes
| Methods | |
| RCT | |
| Location :
Multicenter / UK Follow-up duration (months): 2.7 | |
| BNT/BNT (primary) / mRNA1273 (booster) (n = 111) BNT/BNT (primary) / CVnCov (booster) (n = 106) BNT/BNT (primary) / BNT (half) (booster) (n = 110) BNT/BNT (primary) / MenACWY placebo (n = 112) | |
| Inclusion criteria | Willing and able to give written informed consent; aged 30 years or above; in good health as determined by a trial clinician (may have well controlled or mild-moderate comorbidity; Female participants of childbearing potential must be willing to ensure that they or their partner use effective contraception from 1 month prior to first immunisation continuously until 3 months after boost immunization; able and willing to comply with all trial requirements; Willing to allow their General Practitioner and consultant, if appropriate, to be notified of participation in the trial; Willing to allow investigators to discuss the volunteer’s medical history with their General Practitioner and access all medical records when relevant to study procedures; Agreement to refrain from blood donation during the study; Received priming dose of COVID-19 vaccination in December 2020, January or February 2021 and is at least 84 days post second vaccination. Due to the NHS deployment timelines, some sites may need to invite people who have been prime-boosted with their second dose of AstraZeneca with a minimum of 70 days from their second dose. |
| Exclusion criteria | Receipt of any vaccine (licensed or investigational) other than the study intervention within 30 days before and after each study vaccination (one week for licensed seasonal influenza vaccine or pneumococcal vaccine); Prior or planned receipt of any other investigational or licensed vaccine or product likely to impact on interpretation of the trial data (e.g. adenovirus vectored vaccines, any coronavirus vaccines); Participants who are pregnant at enrolment or planning to become pregnant during the first 3 months following vaccination; Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccines; Any confirmed or suspected immunosuppressive or immunodeficient state; asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 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 study vaccines (e.g. hypersensitivity to the active substance or any of the SmPC-listed ingredients of the Pfizer vaccine); Any history of anaphylaxis; Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ); 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 (i.e. apixaban, rivaroxaban, dabigatran and edoxaban); History of cerebral venous sinus thrombosis, antiphospholipid syndrome or heparin induced thrombocytopenia and thrombosis (HITT or HIT type 2); Suspected or known current alcohol or drug dependency; Any other significant disease, disorder or finding which 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; Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness (mild/moderate well controlled comorbidities are allowed); History of active or previous auto-immune neurological disorders (e.g. multiple sclerosis, Guillain-Barre syndrome, transverse myelitis). Bell’s palsy will not be an exclusion criterion; Significant renal or hepatic impairment; Scheduled elective surgery during the trial; Participant with life expectancy of less than 6 months; Participants who have participated in another research trial involving an investigational product in the past 12 weeks. This does not exclude participants in trials of AZD1222 (ChAdOx1 nCOV-19) who were originally recipients of placebo and who received AZD1222 (ChAdOx1 nCOV-19) or BNT162b2 as part of the “national schedule” with AZD1222 (ChAdOx1 nCOV-19) or BNT162b2 dose 1 from mid-Dec 2020 through end February 2021 and then AZD1222 (ChAdOx1 nCOV-19) or BNT162b2 second dose 12 twelve weeks later (this is allowed by the COV001 and COV002 protocols); Insufficient level of English language to undertake all study requirements in opinion of the Investigators except where translation has been able to be provided and is available. |
| Interventions | |
| Intervention
1 IM 0.1 mg booster dose ≥84 days after primary schedule 1 IM 12 mcg booster dose ≥84 days after primary schedule 1 IM 15 mcg booster dose ≥84 days after primary schedule |
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| Control
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| Participants | |
| Randomized 2883 participants | |
| Characteristics of participants Type of participants: Adults, elderly, health care workers N=2883 208 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: NR | |
| Description of participants Adults aged ≥30 years in good physical health at 18 centers in the UK. | |
| Primary outcome | |
| In the register 1. Immunology measured using serum Anti Spike protein IgG levels at 28 days 2. Safety/Reactogenicity measured using the following from participant records: 2.1. Incidence and details of solicited adverse events between 0 and 7 days 2.2. Incidence and details of unsolicited adverse events between 0 and 28 days 2.3. Incidence and details of Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) throughout the study | |
| In the report Safety and reactogenicity, and immunogenicity. Safety and reactogenicity were determined by the occurrence of solicited, unsolicited adverse events, adverse events of special interest, or serious adverse events following vaccination, as recorded in participant electronic diaries or ascertained at follow-up visits. Immunogenicity outcome was anti-spike protein IgG at day 28 follow-up. | |
| Variants description | |
| Variants | |
| Description Immunogenicity outcomes reported for Delta and Beta variants | |
| Documents avalaible |
Protocol Yes. In English Statistical plan Yes Data-sharing stated:
Yes, On study completion |
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment | In addition to the published article, the registry, protocol, statistical analysis plan and supplementary appendices were used in data extraction and assessment of risk of bias. The primary outcomes in the published article reflected those in the registry. The trial (n = 2883) did not fully achieve its target sample size (n = 2886). |