Clinical trial NCT04444674: COVID-19 Vaccine (ChAdOx1 nCoV-19) Trial in South African Adults With and Without HIV-infection
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Coronavirus
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Medical Research Council, South Africa
name: Bill and Melinda Gates Foundation
name: Wits Health Consortium (Pty) Ltd
name: University of Witwatersrand, South Africa
First posted: 2020-06-23
Enrollment: 2130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Four groups will be enrolled to receive either one or two doses of investigational vaccine or placebo. Follow up intensity and blood draws differ between groups
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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).

Primary outcomes:
measure: 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)
timeFrame: Up to 12 months post enrollment
measure: 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)
timeFrame: Up to 12 months post enrollment
measure: 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)
timeFrame: Up to 12 months post enrollment
measure: Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in people living with HIV (immunogenicity)
timeFrame: Up to 12 months post enrollment
measure: Assess humoral immunogenicity of ChAdOx1 nCoV-19 in people living with HIV
timeFrame: Up to 12 months post enrollment
Secondary outcomes:
measure: Assess humoral Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)
timeFrame: Up to 12 months post enrollment
measure: Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)
timeFrame: Up to 12 months post enrollment
Other outcomes:
measure: Assess Fc effector functionality in participants who receive ChAdOx1 nCoV-19 vaccine or placebo
timeFrame: Up to 12 months post enrollment
measure: 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
timeFrame: Up to 12 months post enrollment
Locations:
city: Johannesburg
country: South Africa
facility: PHRU Kliptown
state: Gauteng
city: Johannesburg
country: South Africa
facility: Soweto Clinical Trials Centre
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits RHI Shandukani Research Centre
state: Gauteng
city: Soshanguve
country: South Africa
facility: Setshaba Research Centre (SRC)
state: Gauteng
city: Soweto
country: South Africa
facility: Chris Hani Baragwanath Academic Hospital - DST/NRF VPD RMPRU
state: Gauteng
city: Cape Town
country: South Africa
facility: FAMCRU
state: Western Cape
city: Cape Town
country: South Africa
facility: Groote Schuur hospital, Lung infection and immunity unit, UCT
state: Western Cape
Study officials:
affiliation: University of Witwatersrand, South Africa
name: Shabir A Madhi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Madhi SA, Kwatra G, Richardson SI, Koen AL, Baillie V, Cutland CL, Fairlie L, Padayachee SD, Dheda K, Barnabas SL, Bhorat QE, Briner C, Ahmed K, Aley PK, Bhikha S, Bhorat AE, Esmail A, Horne E, Kaldine H, Mukendi CK, Madzorera VS, Manamela NP, Masilela M, Hermanus ST, Motlou T, Mzindle N, Oelofse S, Patel F, Rhead S, Rossouw L, Taoushanis C, van Eck S, Lambe T, Gilbert SC, Pollard AJ, Moore PL, Izu A. Durability of ChAdOx1 nCoV-19 (AZD1222) vaccine and hybrid humoral immunity against variants including omicron BA.1 and BA.4 6 months after vaccination (COV005): a post-hoc analysis of a randomised, phase 1b-2a trial. Lancet Infect Dis. 2023 Mar;23(3):295-306. doi: 10.1016/S1473-3099(22)00596-5. Epub 2022 Oct 20.
citation: Madhi SA, Koen AL, Izu A, Fairlie L, Cutland CL, Baillie V, Padayachee SD, Dheda K, Barnabas SL, Bhorat QE, Briner C, Aley PK, Bhikha S, Hermanus T, Horne E, Jose A, Kgagudi P, Lambe T, Masenya M, Masilela M, Mkhize N, Moultrie A, Mukendi CK, Moyo-Gwete T, Nana AJ, Nzimande A, Patel F, Rhead S, Taoushanis C, Thombrayil A, van Eck S, Voysey M, Villafana TL, Vekemans J, Gilbert SC, Pollard AJ, Moore PL, Kwatra G; Wits VIDA COVID team. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial. Lancet HIV. 2021 Sep;8(9):e568-e580. doi: 10.1016/S2352-3018(21)00157-0. Epub 2021 Aug 17.
citation: Madhi SA, Baillie V, Cutland CL, Voysey M, Koen AL, Fairlie L, Padayachee SD, Dheda K, Barnabas SL, Bhorat QE, Briner C, Kwatra G, Ahmed K, Aley P, Bhikha S, Bhiman JN, Bhorat AE, du Plessis J, Esmail A, Groenewald M, Horne E, Hwa SH, Jose A, Lambe T, Laubscher M, Malahleha M, Masenya M, Masilela M, McKenzie S, Molapo K, Moultrie A, Oelofse S, Patel F, Pillay S, Rhead S, Rodel H, Rossouw L, Taoushanis C, Tegally H, Thombrayil A, van Eck S, Wibmer CK, Durham NM, Kelly EJ, Villafana TL, Gilbert S, Pollard AJ, de Oliveira T, Moore PL, Sigal A, Izu A; NGS-SA Group; Wits-VIDA COVID Group. Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med. 2021 May 20;384(20):1885-1898. doi: 10.1056/NEJMoa2102214. Epub 2021 Mar 16.
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