A Study of a Candidate COVID-19 Vaccine (COV001)

• ClinicalTrials.gov Identifier: NCT04324606
• Recruitment Status: Active, not recruiting
• First Posted: March 27, 2020
• Last Update Posted: November 18, 2020
• Sponsor: University of Oxford
• Information provided by (Responsible Party): University of Oxford

Tracking Information

• First Submitted Date: March 20, 2020
• First Posted Date: March 27, 2020
• Last Update Posted Date: November 18, 2020
• Actual Study Start Date: April 23, 2020
• Estimated Primary Completion Date: October 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 16, 2020)

• Assess efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19: Number of virologically confirmed (PCR positive) symptomatic cases [ Time Frame: 6 months ]
  Number of virologically confirmed (PCR or NAAT positive) symptomatic cases of COVID-19
• Assess the safety of the candidate vaccine ChAdOx1 nCoV: Occurrence of serious adverse events (SAEs) [ Time Frame: 6 months ]
  Occurrence of serious adverse events (SAEs) throughout the study duration

Original Primary Outcome Measures (submitted: March 26, 2020)

• Assess efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19: Number of virologically confirmed (PCR positive) symptomatic cases [ Time Frame: 6 months ]
  Number of virologically confirmed (PCR positive) symptomatic cases of COVID-19
• Assess the safety of the candidate vaccine ChAdOx1 nCoV: Occurrence of serious adverse events (SAEs) [ Time Frame: 6 months ]
  Occurrence of serious adverse events (SAEs) throughout the study duration

Current Secondary Outcome Measures (submitted: September 30, 2020)

• Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of solicited local reactogenicity signs and symptoms [ Time Frame: 7 days following vaccination ]
  Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination
• Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of solicited systemic reactogenicity signs and symptoms [ Time Frame: 7 days following vaccination ]
  Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination
• Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of unsolicited adverse events (AEs) [ Time Frame: 28 days following vaccination ]
  Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination
• Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV through standard blood tests [ Time Frame: 6 months ]
  Change from baseline for safety laboratory measures (haematology and biochemistry blood results)
• Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV by measuring the number of disease enhancement episodes [ Time Frame: 6 months ]
  Occurrence of disease enhancement episodes
• Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by hospital admissions [ Time Frame: 6 months ]
  Number of hospital admissions associated with COVID-19
• Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by ICU admissions [ Time Frame: 6 months ]
  Number of intensive care unit admissions associated with COVID-19
• Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by COVID-19 related deaths [ Time Frame: 6 months ]
  Number of deaths associated with COVID-19
• Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 [ Time Frame: 6 months ]
  Occurrence of severe COVID-19 disease (defined according to clinical severity scales)
• Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring seroconversion rates [ Time Frame: 6 months ]
  Proportion of people who become seropositive for non-Spike SARS-CoV-2 antigens during the study
• Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through ELISpot assays [ Time Frame: 6 months ]
  Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein
• Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 [ Time Frame: 6 months ]
  Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates)

Original Secondary Outcome Measures (submitted: March 26, 2020)

• Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of solicited local reactogenicity signs and symptoms [ Time Frame: 7 days following vaccination ]
  Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination
• Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of solicited systemic reactogenicity signs and symptoms [ Time Frame: 7 days following vaccination ]
  Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination
• Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of unsolicited adverse events (AEs) [ Time Frame: 28 days following vaccination ]
  Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination
• Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV through standard blood tests [ Time Frame: 6 months ]
  Change from baseline for safety laboratory measures (haematology and biochemistry blood results)
• Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV by measuring the number of disease enhancement episodes [ Time Frame: 6 months ]
  Occurrence of disease enhancement episodes
• Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 [ Time Frame: 6 months ]
  Number of deaths associated with COVID-19
• Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 [ Time Frame: 6 months ]
  Number of hospital admissions associated with COVID-19
• Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 [ Time Frame: 6 months ]
  Number of intensive care unit admissions associated with COVID-19
• Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring seroconversion rates [ Time Frame: 6 months ]
  Proportion of people who become seropositive for non-Spike SARS-CoV-2 antigens during the study
• Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through ELISpot assays [ Time Frame: 6 months ]
  Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein
• Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 [ Time Frame: 6 months ]
  Enzyme-linked immunosorbent assay (ELISA) to quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates)

Current Other Pre-specified Outcome Measures (submitted: November 16, 2020)

• Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through Virus neutralising antibody assays [ Time Frame: 6 months ]
  Virus neutralising antibody (NAb) assays against live and/or pseudotype SARS-CoV-2 virus
• Assess safety, reactogenicity, immunogenicity and efficacy endpoints, for participants receiving prophylactic paracetamol [ Time Frame: 6 months ]
  All safety, reactogenicity, immunogenicity and efficacy endpoints
• Assess immunogenicity of ChAdOx1 nCoV-19 given as homologous prime-boost [ Time Frame: 6 months ]
  Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) post boost
• Compare viral shedding on stool samples of SARS-CoV-2 PCR or NAAT positive individuals [ Time Frame: 6 months ]
  Differences in viral shedding on stool between vaccine and comparator arms at 7 days and beyond post SARS-CoV-2 PCR or NAAT positivity

Original Other Pre-specified Outcome Measures (submitted: March 26, 2020)

Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through Virus neutralising antibody assays [ Time Frame: 6 months ]

Virus neutralising antibody (NAb) assays against live and/or pseudotype SARS-CoV-2 virus

Descriptive Information

• Brief Title: A Study of a Candidate COVID-19 Vaccine (COV001)
• Official Title: A Phase I/II Study to Determine Efficacy, Safety and Immunogenicity of the Candidate Coronavirus Disease (COVID-19) Vaccine ChAdOx1 nCoV-19 in UK Healthy Adult Volunteers
• Brief Summary: A phase I/II single-blinded, randomised, multi-centre study to determine efficacy, safety and immunogenicity of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19 in UK healthy adult volunteers aged 18-55 years. The vaccine will be administered intramuscularly (IM) into the deltoid region of the arm
• Detailed Description: There will be 4 study groups and it is anticipated that a total of 1090 volunteers will be enrolled. Volunteers will participate in the study for approximately 12 months from last vaccination visit (approximately 15 months from enrolment for participants receiving 2 doses)
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Coronavirus

Intervention

• Biological: ChAdOx1 nCoV-19
  A single dose of 5x10^10vp of ChAdOx1 nCoV-19
• Biological: MenACWY
  Standard single dose of MenACWY vaccine delivered intramuscularly
• Biological: ChAdOx1 nCoV-19 full boost
  A single dose of 5x10^10vp of ChAdOx1 nCoV-19 followed by a boost dose of 5x10^10vp of ChAdOx1 nCoV-19
• Biological: ChAdOx1 nCoV-19 half boost
  A single dose of 5x10^10vp of ChAdOx1 nCoV-19 followed by a boost dose of 2.5x10^10vp of ChAdOx1 nCoV-19
• Biological: MenACWY boost
  A standard dose of MenACWY followed by a boost dose of MenACWY
• Drug: Paracetamol
  1g every 6 hours for 24 hours
• Biological: ChAdOx1 nCoV-19 0.5mL boost
  A single dose of 5x10^10vp of ChAdOx1 nCoV-19 followed by a boost dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x1010vp)

Study Arms

• Experimental: Group 1a
  Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 delivered intramuscularly
  Intervention: Biological: ChAdOx1 nCoV-19
• Active Comparator: Group 1b
  Volunteers will receive a standard single dose of MenACWY vaccine delivered intramuscularly
  Intervention: Biological: MenACWY
• Experimental: Group 2a
  Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 delivered intramuscularly
  Intervention: Biological: ChAdOx1 nCoV-19
• Active Comparator: Group 2b
  Volunteers will receive a standard single dose of MenACWY vaccine delivered intramuscularly
  Intervention: Biological: MenACWY
• Experimental: Group 2c
  Volunteers will receive two doses of 5x10^10vp ChAdOx1 nCoV-19 delivered intramuscularly at week 0 and week 8
  Intervention: Biological: ChAdOx1 nCoV-19 full boost
• Experimental: Group 2d
  Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 at week 0 and a boost dose of 2.5x10^10vp ChAdOx1 nCoV-19 at week 8 delivered intramuscularly
  Intervention: Biological: ChAdOx1 nCoV-19 half boost
• Active Comparator: Group 2e
  Volunteers will receive two standard single doses of MenACWY vaccine delivered intramuscularly at week 0 and week 8
  Intervention: Biological: MenACWY boost
• Experimental: Group 2f
  Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 at week 0 and a boost dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x1010vp) a minimum of 4 weeks later, delivered intramuscularly
  Intervention: Biological: ChAdOx1 nCoV-19 0.5mL boost
• Active Comparator: Group 2g
  Volunteers will receive two standard single doses of MenACWY vaccine delivered intramuscularly a minimum of 4 weeks apart
  Intervention: Biological: MenACWY boost
• Experimental: Group 3
  Volunteers will receive one dose of 5x10^10vp ChAdOx1 nCoV-19 at week 0 and one dose of 5x10^10vp ChAdOx1 nCoV-19 at week 4 delivered intramuscularly
  Intervention: Biological: ChAdOx1 nCoV-19 full boost
• Experimental: Group 4a
  Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 delivered intramuscularly
  Interventions:

  • Biological: ChAdOx1 nCoV-19
  • Drug: Paracetamol
• Active Comparator: Group 4b
  Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 delivered intramuscularly
  Interventions:

  • Biological: MenACWY
  • Drug: Paracetamol
• Experimental: Group 4c
  Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 at week 0 and a boost dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x1010vp) a minimum of 4 weeks later, delivered intramuscularly
  Interventions:

  • Biological: ChAdOx1 nCoV-19
  • Biological: ChAdOx1 nCoV-19 0.5mL boost
• Active Comparator: Group 4d
  Volunteers will receive two standard single doses of MenACWY vaccine delivered intramuscularly a minimum of 4 weeks apart
  Intervention: Biological: MenACWY boost

Publications *

• Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Collins AM, Colin-Jones R, Cutland CL, Darton TC, Dheda K, Duncan CJA, Emary KRW, Ewer KJ, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Goodman AL, Green CM, Green CA, Heath PT, Hill C, Hill H, Hirsch I, Hodgson SHC, Izu A, Jackson S, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Lawrie AM, Lelliott A, Libri V, Lillie PJ, Mallory R, Mendes AVA, Milan EP, Minassian AM, McGregor A, Morrison H, Mujadidi YF, Nana A, O'Reilly PJ, Padayachee SD, Pittella A, Plested E, Pollock KM, Ramasamy MN, Rhead S, Schwarzbold AV, Singh N, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Tarrant R, Thomson EC, Török ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, Watson MEE, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ; Oxford COVID Vaccine Trial Group. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2020 Dec 8. pii: S0140-6736(20)32661-1. doi: 10.1016/S0140-6736(20)32661-1. [Epub ahead of print]
• Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, Bellamy D, Bibi S, Bittaye M, Clutterbuck EA, Dold C, Faust SN, Finn A, Flaxman AL, Hallis B, Heath P, Jenkin D, Lazarus R, Makinson R, Minassian AM, Pollock KM, Ramasamy M, Robinson H, Snape M, Tarrant R, Voysey M, Green C, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ; Oxford COVID Vaccine Trial Group. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020 Aug 15;396(10249):467-478. doi: 10.1016/S0140-6736(20)31604-4. Epub 2020 Jul 20. Erratum in: Lancet. 2020 Aug 15;396(10249):466. Erratum in: Lancet. 2020 Dec 12;396(10266):1884.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 7, 2020): 1090
• Original Estimated Enrollment (submitted: March 26, 2020): 510
• Estimated Study Completion Date: October 2021
• Estimated Primary Completion Date: October 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

The volunteer must satisfy all the following criteria to be eligible for the study:

• Healthy adults aged 18-55 years.
• Able and willing (in the Investigator's opinion) to comply with all study requirements (participants must not rely on public transport or taxis).
• 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.
• For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and vaccination.
• Agreement to refrain from blood donation during the course of the study.
• Provide written informed consent.

Exclusion Criteria

The volunteer may not enter the study if any of the following apply:

• Planned receipt of any vaccine other than the study intervention within 30 days before and after each study vaccination .with the exception of the licensed seasonal influenza vaccination and the licensed pneumococcal vaccine. Participants will be encouraged to receive this vaccination at least 7 days before or after their study vaccine.
• Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines).
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; 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) .
• Any autoimmune conditions, except mild psoriasis, well-controlled autoimmune thyroid disease, vitiligo or stable coeliac disease not requiring immunosuppressive or immunomodulatory therapy.
• History of allergic disease or reactions likely to be exacerbated by any component of the ChAdOx1 nCoV-19 or MenACWY vaccines.
• Any history of angioedema .
• Any history of anaphylaxis .
• Pregnancy, lactation or willingness/intention to become pregnant during the study.
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
• History of serious psychiatric condition likely to affect participation in the study (e.g. ongoing severe depression, history of admission to an in-patient psychiatric facility, recent suicidal ideation, history of suicide attempt, bipolar disorder, personality disorder, alcohol and drug dependency, severe eating disorder, psychosis, use of mood stabilisers or antipsychotic medication).
• Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture.
• Any other serious chronic illness requiring hospital specialist supervision.
• Chronic respiratory diseases, including mild asthma (resolved childhood asthma is allowed)
• Chronic cardiovascular disease (including hypertension), gastrointestinal disease, liver disease (except Gilberts Syndrome), renal disease, endocrine disorder (including diabetes) and neurological illness (excluding migraine)
• Seriously overweight (BMI≥40 Kg/m2) or underweight (BMI≤18 Kg/m2)
• Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week.
• Suspected or known injecting drug abuse in the 5 years preceding enrolment.
• Any clinically significant abnormal finding on screening biochemistry, haematology blood tests or urinalysis.
• 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.
• History of laboratory confirmed COVID-19.
• New onset of fever or a cough or shortness of breath or anosmia/ageusia since February 2020. Should a reliable test become available, this exclusion criteria will be replaced with seropositivity for SARS-CoV-2 before enrolment.
• Those who have been at high risk of exposure before enrolment, including but not limited to: close contacts of confirmed COVID-19 cases, anyone who had to self-isolate as a result of a symptomatic household member, frontline healthcare professionals working in A&E, ICU and other higher risk areas. Should a reliable test become available, this exclusion criteria will be replaced with seropositivity for SARS-CoV-2 before enrolment.
• Living in the same household as any vulnerable groups at risk of severe COVID-19 disease (as per Public Health England guidance)

Additional exclusion criteria (subset of participants receiving Paracetamol in group 4 only)

• History of allergic disease or reactions likely to be exacerbated by Paracetamol

Re-vaccination exclusion criteria:

The following AEs associated with any vaccine, or identified on or before the day of vaccination constitute absolute contraindications to further administration of an IMP to the volunteer in question. If any of these events occur during the study, the subject will not be eligible to receive a booster dose and will be followed up by the clinical team or their GP until resolution or stabilisation of the event:

• Anaphylactic reaction following administration of vaccine
• Pregnancy
• Any AE that in the opinion of the Investigator may affect the safety of the participant or the interpretation of the study results

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT04324606
• Other Study ID Numbers: COV001
• 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
• Responsible Party: University of Oxford
• Study Sponsor: University of Oxford
• Collaborators: Not Provided

Investigators

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

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