Clinical trial NCT04536051: A Study of a Candidate COVID-19 Vaccine (COV003)
Official title: A Randomized, Controlled, Phase III Study to Determine the Safety, Efficacy, and Immunogenicity of the Non-Replicating ChAdOx1 nCoV-19 Vaccine
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Coronavirus
Keywords: Covid-19
ChAdOx1 nCov19
sars-cov-2
vaccine
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2020-09-02
Enrollment: 10300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: A Randomized, Controlled, Phase III Study to Determine the Safety, Efficacy, and Immunogenicity of the Non-Replicating ChAdOx1 nCoV-19 Vaccine.

Detailed description: There will be 2 study groups and an anticipated enrolment of 10,300 health professionals and adults with high potential for exposure to SARS-CoV-2, aged ≥18 years.

All subjects will undergo follow-up for a total of 1 year post last vaccination. Additional visits or procedures may be performed at the discretion of the investigators, e.g., further medical history and physical examination, or additional blood tests and other investigations if clinically relevant

Eligibility criteria: Inclusion Criteria:

* Adults from 18 to 55 years of age
* Adults aged 56-69 years old (after review of safety data by DSMB in this age group in the UK trial)
* Adults aged 70 and above years old (after review of safety data by DSMB in this age group in the UK trial)
* Able and willing (in the Investigator's opinion) to fulfill all study requirements;
* Health professionals and adults at high risk of exposure to SARS-CoV-2, as defined in section 5.2 of this protocol;
* Serology with SARS-CoV-2 negative IgG antibodies; This inclusion criteria does not apply to participants enrolled from version 4.0 of the protocol onwards.
* Willing to allow investigators to discuss the participant's clinical history with their GP/personal physician and access medical records relevant to the study procedures
* Only for women of childbearing age willing to practice continuous effective birth control (see below) during the study, and a negative pregnancy test on the screening and vaccination day(s);
* Consent to abstain from blood donation during the course of the study;
* Provide informed consent in writing

Exclusion Criteria:

* Participation in trials of prophylactic drugs for COVID-19 during the course of the study; Note: Participation in COVID-19 treatment trials is permitted in case of hospitalization due to COVID-19, after confirmation of positive PCR. The study team should be informed as soon as possible. Participants with COVID-19 not hospitalized with positive PCR results for COVID-19 may be medicated according to standard clinical practice.
* Participation in SARS-CoV-2 serological research where participants are informed of their serological status during the course of the study;
* Planned receipt of any vaccine (authorized or investigational), within 30 days before and after vaccination;
* Prior receipt of an investigational vaccine or authorized with the possibility of impacting the interpretation of the study data (for example, vaccines vectorized by Adenovirus, any vaccines against coronavirus);
* Administration of immunoglobulins and/or any blood products in the three months prior to the planned administration of the candidate vaccine;
* Any confirmed or suspected immunosuppressive or immunodeficiency state; asplenia; severe recurrent infections and chronic use (more than 14 days) of immunosuppressive medication in the last 6 months, except for topical steroids or short-term oral steroids (cycle lasting ≤14 days);
* History of allergic disease or reactions possibly exacerbated by any component of ChAdOx1 nCoV-19 or MenACWY or paracetamol;
* Any history of angioedema;
* Any history of anaphylaxis;
* Pregnancy, lactation or willingness/intention to become pregnant during the study;
* Current diagnosis or treatment for cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ);
* History of severe psychiatric illness that possibly affects your participation in the study;
* Hemorrhagic disorder (for example, factor deficiency, coagulopathy or platelet disorder), or a previous history of significant bleeding or bruising after IM injections or venipuncture;
* Current suspected or known dependence on alcohol or drugs;
* Severe and/or uncontrolled cardiovascular diseases, respiratory diseases, gastrointestinal diseases, liver disease, kidney disease, endocrine disorder, and neurological disease (mild/moderate well-controlled comorbidities are allowed);
* History of COVID-19 confirmed by laboratory;
* Seropositive for antibodies to SARS-CoV-2 before recruitment; This exclusion criteria does not apply to participants enrolled from version 4.0 of the protocol onwards
* Continued use of anticoagulants, such as coumarins and related anticoagulants (for example, warfarin) or new oral anticoagulants (for example, apixaban, rivaroxaban, dabigatran and edoxaban);
* Any other significant illness, disorder or finding that may significantly increase the risk for the participant, affect his/her ability to participate in the study or impair the interpretation of the study data.

Re-vaccination exclusion criteria (two-dose groups only)

* Anaphylactic reaction following administration of vaccine
* Pregnancy

Primary outcomes:
measure: Evaluate the efficacy of ChAdOx1 nCoV-19 vaccine against COVID-19 disease confirmed with PCR
timeFrame: 12 months post final vaccination
Secondary outcomes:
measure: Evaluate the safety, tolerability and reactogenicity profile of ChAdOx1 nCoV-19 candidate vaccine: occurrence of signs and symptoms of local and systemic reactogenicity requested during 7 days after vaccination
timeFrame: 7 days post vaccination
measure: Evaluate the safety, tolerability and reactogenicity profile of ChAdOx1 nCoV-19 candidate vaccine: occurrence of serious adverse events
timeFrame: 12 months post final vaccination
measure: Evaluate the safety, tolerability and reactogenicity profile of ChAdOx1 nCoV-19 candidate vaccine: occurrence of episodes; intensified disease
timeFrame: 12 months post final vaccination
measure: Evaluate the efficacy of ChAdOx1 nCoV-19 candidate vaccine against severe and non-severe COVID-19 disease: hospitalization for COVID-19 disease confirmed by PCR
timeFrame: 12 months post final vaccination
measure: Evaluate the efficacy of ChAdOx1 nCoV-19 candidate vaccine against severe and non-severe COVID-19 disease: COVID-19 serious disease confirmed by PCR
timeFrame: 12 months post final vaccination
measure: Evaluate the efficacy of ChAdOx1 nCoV-19 candidate vaccine against severe and non-severe COVID-19 disease: death associated with COVID-19 disease
timeFrame: 6 months
measure: Evaluate the efficacy of ChAdOx1 nCoV-19 candidate vaccine against severe and non-severe COVID-19 disease: antibodies against SARS-CoV-2 non-Spike protein (serum efficacy rates)
timeFrame: 12 months post final vaccination
measure: Evaluate the humoral immunogenicity of ChAdOx1 nCoV-19: antibodies against the SARS-CoV-2 spike protein (serum conversion rates)
timeFrame: 12 months post final vaccination
measure: Evaluate the humoral immunogenicity of ChAdOx1 nCoV-19: virus neutralizing antibodies (NAb) against live and/or pseudotyped SARS-CoV-2 virus
timeFrame: 12 months post final vaccination
measure: Assess the cellular immunogenicity of ChAdOx1 nCoV-19 candidate vaccine
timeFrame: 12 months post final vaccination
Other outcomes:
Locations:
city: Salvador
country: Brazil
facility: Instituto D'Or de Pesquisa e Ensino - I'Dor
state: Bahia
city: Natal
country: Brazil
facility: Centro de Pesquisas Clinicas de Natal (CPCLIN)
state: Rio Grande Do Norte
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas de Porto Alegre
state: Rio Grande Do Sul
city: Santa Maria
country: Brazil
facility: Universidade Federal de Santa Maria (UFSM)
state: Rio Grande Do Sul
city: Rio de Janeiro
country: Brazil
facility: Instituto D'Or de Pesquisa e Ensino - I'Dor
city: São Paulo
country: Brazil
facility: CRIE, Universidade Federal de São Paulo
Study officials:
affiliation: University of Oxford
name: Andrew Pollard, Prof
role: PRINCIPAL_INVESTIGATOR
References: