A Study of a Candidate COVID-19 Vaccine (COV003)

• ClinicalTrials.gov Identifier: NCT04536051
• Recruitment Status: Unknown
• First Posted: September 2, 2020
• Last Update Posted: November 27, 2020
• Sponsor: University of Oxford
• Information provided by (Responsible Party): University of Oxford

Tracking Information

• First Submitted Date: September 1, 2020
• First Posted Date: September 2, 2020
• Last Update Posted Date: November 27, 2020
• Actual Study Start Date: June 2, 2020
• Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 1, 2020)

Evaluate the efficacy of ChAdOx1 nCoV-19 vaccine against COVID-19 disease confirmed with PCR [ Time Frame: 12 months post final vaccination ]

COVID-19 virologically confirmed symptomatic cases (PCR positive).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 1, 2020)

• 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 [ Time Frame: 7 days post vaccination ]
  Occurrence of signs and symptoms of local and systemic reactogenicity requested during 7 days after vaccination (in a subset of 200 participants)
• Evaluate the safety, tolerability and reactogenicity profile of ChAdOx1 nCoV-19 candidate vaccine: occurrence of serious adverse events [ Time Frame: 12 months post final vaccination ]
  Occurrence of serious adverse events
• Evaluate the safety, tolerability and reactogenicity profile of ChAdOx1 nCoV-19 candidate vaccine: occurrence of episodes; intensified disease [ Time Frame: 12 months post final vaccination ]
  Occurrence of episodes; intensified disease
• 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 [ Time Frame: 12 months post final vaccination ]
  Hospitalization for COVID-19 disease confirmed by PCR
• Evaluate the efficacy of ChAdOx1 nCoV-19 candidate vaccine against severe and non-severe COVID-19 disease: COVID-19 serious disease confirmed by PCR [ Time Frame: 12 months post final vaccination ]
  COVID-19 serious disease confirmed by PCR
• Evaluate the efficacy of ChAdOx1 nCoV-19 candidate vaccine against severe and non-severe COVID-19 disease: death associated with COVID-19 disease [ Time Frame: 6 months ]
  Death associated with COVID-19 disease
• 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) [ Time Frame: 12 months post final vaccination ]
  Antibodies against SARS-CoV-2 non-Spike protein (serum efficacy rates).
• Evaluate the humoral immunogenicity of ChAdOx1 nCoV-19: antibodies against the SARS-CoV-2 spike protein (serum conversion rates) [ Time Frame: 12 months post final vaccination ]
  Antibodies against the SARS-CoV-2 spike protein (serum conversion rates)
• Evaluate the humoral immunogenicity of ChAdOx1 nCoV-19: virus neutralizing antibodies (NAb) against live and/or pseudotyped SARS-CoV-2 virus [ Time Frame: 12 months post final vaccination ]
  Virus neutralizing antibodies (NAb) against live and/or pseudotyped SARS-CoV-2 virus
• Assess the cellular immunogenicity of ChAdOx1 nCoV-19 candidate vaccine [ Time Frame: 12 months post final vaccination ]
  Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Single (Participant); Primary Purpose: Prevention
• Condition: Coronavirus

Intervention

• Biological: ChAdOx1 nCoV-19 single dose + paracetamol
  Single dose of ChAdOx1nCOV19 vaccine, 5x10^10 vp + paracetamol
• Biological: MenACWY single dose + paracetamol
  Single dose of MenACWY + paracetamol
• Biological: ChAdOx1 nCoV-19 two dose + paracetamol
  Two dose of ChAdOx1 nCoV-19 vaccine, 5x10^10vp (prime) and 0.5mL boost (3.5 - 6.5 × 10^10 vp), 4-12 weeks apart + paracetamol
• Biological: MenACWY prime & saline placebo boost + paracetamol
  MenACWY prime, and Saline Placebo boost (0.5mL) + paracetamol

Study Arms

• Experimental: Group 1a: single dose ChAdOx & paracetamol
  Participants will receive a single standard dose of ChAdOx1 nCOV19 vaccine plus paracetamol
  Intervention: Biological: ChAdOx1 nCoV-19 single dose + paracetamol
• Active Comparator: Group 1b: single dose MenACWY & paracetamol
  Participants will receive a single dose of MenACWY plus paracetamol
  Intervention: Biological: MenACWY single dose + paracetamol
• Experimental: Group 1c: two dose ChAdOx & paracetamol
  Participants will receive two standard doses of ChAdOx1 nCoV-19 vaccine, 4-12 weeks apart, plus paracetamol
  Intervention: Biological: ChAdOx1 nCoV-19 two dose + paracetamol
• Active Comparator: Group 1d: two dose MenACWy/saline & paracetamol
  Participants will receive MenACWY prime, and Saline Placebo boost (0.5mL) plus paracetamol
  Intervention: Biological: MenACWY prime & saline placebo boost + paracetamol

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 23, 2020): 10300
• Original Estimated Enrollment (submitted: September 1, 2020): 5000
• Estimated Study Completion Date: September 2021
• Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT04536051
• Other Study ID Numbers: COV003
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Oxford
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Oxford
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Andrew Pollard, Prof; University of Oxford

• PRS Account: University of Oxford
• Verification Date: September 2020