COVID-19 Vaccine (ChAdOx1 nCoV-19) Trial in South African Adults With and Without HIV-infection

Coronavirus Clinical Trial

Official title:

An Adaptive Phase I/II Randomized Placebo-controlled Trial to Determine Safety, Immunogenicity and Efficacy of Non-replicating ChAdOx1 SARS-CoV-2 Vaccine in South African Adults Living Without HIV; and Safety and Immunogenicity in Adults Living With HIV

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04444674
• Other study ID #: ChAdOx1 nCoV-19_ZA_phI/II v4.1
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 24, 2020
• Est. completion date: December 2021

Study information

• Verified date: November 2020
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase I/II, double-blinded, placebo-controlled, individually randomized trial to assess safety, immunogenicity and efficacy of the candidate Coronavirus disease (COVID-19) vaccine ChAdOx1 nCoV-19 in adults aged 18-65 years living with and without HIV in South Africa. The vaccine or placebo will be administered via an intramuscular injection into the deltoid muscle of the non-dominant arm.

Description:

A total of 2070 participants will be enrolled into the trial; 1970 HIV-uninfected and 100 people living with HIV. There will be 4 trial groups, group 1 (n=50; intensive safety & immunogenicity cohort, HIV negative), group 2a (n=250; safety, intense immunogenicity & efficacy), group 2b (n=1650; safety, immunogenicity & vaccine efficacy) and group 3 (n=100, intensive safety & immunogenicity cohort, HIV positive). Participants will be followed up for 12 months after enrollment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2130
• Est. completion date: December 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Healthy adults aged 18-65 years.
• Documented result of not being infected with HIV (including screening by a rapid HIV antibody test) within two weeks of randomization into the study for Group-1 and Group-2 participants only.
• Able and willing (in the Investigator's opinion) to comply with all study requirements.
• Willing to allow investigators review available medical records, and review all medical and laboratory records if participant is admitted to hospital with respiratory tract infection suspected or confirmed to be COVID-19.
• 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 (within 14 days of randomization) or vaccination.
• For Group-3 only (i.e. HIV-infected), need to have been on anti-retroviral treatment for at least three months and HIV-1 viral load is <1,000 copies/ml within two weeks of randomization.
• Agreement to refrain from blood donation during the course of the study.
• Provide written informed consent.

Exclusion Criteria:

• Planned receipt of any vaccine other (licensed or investigational) than the study intervention within 30 days before and after each study vaccination.
• Use of any unproven registered and unregistered treatments for COVID-19.
• 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.
• HBSAg positivity on the screening sample.
• Grade 2 or higher level of abnormality for FBC, U&E or LFT based on DAIDS Grading Criteria (Version 2.1, July 2017)
• History of allergic disease or reactions likely to be exacerbated by any component of the ChAdOx1 nCoV-19 vaccine.
• Any history of hereditary angioedema or idiopathic angioedema.
• Any history of anaphylaxis in relation to vaccination.
• 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.
• Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture.
• Any other serious chronic illness requiring hospital specialist supervision.
• Chronic respiratory diseases, including asthma
• Chronic cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness
• Seriously overweight (BMI = 40 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 enrollment.
• Any clinically significant abnormal finding on screening urinalysis.
• Any other significant disease, disorder or finding which may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study or impair interpretation of the study data.
• History of laboratory confirmed COVID-19 illness or known contact with a person that was infected with SARS-COV-2.
• New onset of fever or a cough or shortness of breath in the 30 days preceding screening and/or enrollment
• Travel history to any other country with widespread epidemic since January 2020
• In addition to above, Group 1 & 2 participants need to fulfill the following exclusion criteria: Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent severe infections and chronic use (more than 14 days) immunosuppressant medication within the past 6 months ( topical steroids are allowed).
• Any confirmed or suspected immunosuppressive or immunodeficient state (except HIV infection for Group-3), asplenia, recurrent severe infections and chronic use (more than 14 days) immunosuppressant medication within the past 6 months (topical steroids are allowed).

Related Conditions & MeSH terms

• Coronavirus
• Coronavirus Infections

Intervention

Biological:
• ChAdOx1 nCoV-19
Dose of 5-7.5x10^10vp of ChAdOx1 nCoV-19
• Normal saline 0.9%
Normal saline 0.9% as placebo

Locations

Country	Name	City	State
South Africa	FAMCRU	Cape Town	Western Cape
South Africa	Groote Schuur hospital, Lung infection and immunity unit, UCT	Cape Town	Western Cape
South Africa	PHRU Kliptown	Johannesburg	Gauteng
South Africa	Soweto Clinical Trials Centre	Johannesburg	Gauteng
South Africa	Wits RHI Shandukani Research Centre	Johannesburg	Gauteng
South Africa	Setshaba Research Centre (SRC)	Soshanguve	Gauteng
South Africa	Chris Hani Baragwanath Academic Hospital - DST/NRF VPD RMPRU	Soweto	Gauteng

Sponsors (5)

Lead Sponsor	Collaborator
University of Oxford	Bill and Melinda Gates Foundation, Medical Research Council, South Africa, University of Witwatersrand, South Africa, Wits Health Consortium (Pty) Ltd

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assess Fc effector functionality in participants who receive ChAdOx1 nCoV-19 vaccine or placebo	Cellular Fc effector functionality assays to measure the ability of vaccine elicited antibodies to mediate cellular cytotoxicity, complement deposition, and phagocytosis.	Up to 12 months post enrollment
Other	Assess B cell responses to SARS-CoV-2 spike trimer and/or the receptor binding domain in participants who receive ChAdOx1 nCoV-19 vaccine or placebo	Flow cytometric sorting of plasmablasts and memory B cells to using spike and receptor binding domain "baits" to isolate SARS-CoV-2 specific B cells, sequence their immunoglobulin genes and define their epitope specificity.	Up to 12 months post enrollment
Primary	Assess the incidence of adverse events (intervention-related and intervention-unrelated) in HIV-negative adults aged 18-65 year receiving candidate ChAdOx1 nCoV-19 vaccine or placebo (safety)	Number of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination, and unsolicited adverse events for 28 days following vaccination.; Assess occurrence of disease enhancement episodes and serious adverse events in year post vaccination	Up to 12 months post enrollment
Primary	Determine if there is a reduction of severe and non-severe COVID-19 disease in HIV-negative adults who receive candidate vaccine ChAdOx1 nCoV-19 compared to placebo recipients (efficacy)	Virologically-confirmed COVID-19 clinical disease will be defined as an acute respiratory illness that is clinically consistent with COVID-19 disease, AND SARS-CoV-2 RT-PCR positivity.	Up to 12 months post enrollment
Primary	Assess the incidence of adverse events (intervention-related and intervention-unrelated) in HIV-positive adults aged 18-65 year receiving candidate ChAdOx1 nCoV-19 vaccine or placebo (safety)	Number of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination, and unsolicited adverse events for 28 days following vaccination.; Assess occurrence of disease enhancement episodes and serious adverse events in year post vaccination	Up to 12 months post enrollment
Primary	Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in people living with HIV (immunogenicity)	Assessing the Interferon-gamma (IFN-?) enzyme- linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein and Th1 and Th2 cytokine response profile at 3-4 days after vaccination	Up to 12 months post enrollment
Primary	Assess humoral immunogenicity of ChAdOx1 nCoV-19 in people living with HIV	Assessing Enzyme-linked immunosorbent assay (ELISA) or fluorescence based micro-bead immunosorbent assay on luminex platform to quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) and Virus neutralising antibody (NAb) assays against live and/or pseudotyped SARS-CoV-2 virus	Up to 12 months post enrollment
Secondary	Assess humoral Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)	Assessing Enzyme-linked immunosorbent assay (ELISA) or fluorescence based micro-bead immunosorbent assay on luminex platform to quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) and Virus neutralising antibody (NAb) assays against live and/or pseudotyped SARS-CoV-2 virus	Up to 12 months post enrollment
Secondary	Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)	Assessing the Interferon-gamma (IFN-?) enzyme- linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein and Th1 and Th2 cytokine response profile at 3-4 days after vaccination	Up to 12 months post enrollment