HIV-1-infectionPhase 1HIV-CORE 006NCT04553016
A Study to Test Three Experimental HIV Vaccines in Healthy Adults.
A Phase 1 study testing Vaccine in people with HIV-1-infection, run by University of Oxford at 4 sites in 3 countries.
Trial summary
HIV-CORE 006 is a Phase 1 double-blind placebo-controlled trial, in which the mosaic immunogens are delivered by a prime-boost regimen of non-replicating simian adenovirus followed by non-replicating poxvirus MVA. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 16 Aug 2021to Nov 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male and female as assessed by a medical history, physical exam, and laboratory tests.
- At low risk of HIV infection and willing to maintain low-risk behaviour for the duration of the trial. Individuals from key populations are not excluded provided they are assessed to be at low risk of HIV infection at screening and are willing to maintain low-risk behaviour during the study.
- At least 18 years of age on the day of screening and have not reached their 51st birthday on the day of the first vaccination.
- Willing and able to give informed consent for participation in the trial before any study-related procedures are performed. Volunteers will pass an Assessment of Understanding before signing the consent form.
- Willing to comply with the requirements of the protocol and be available for follow up for the planned duration of the study.
- Willing to undergo HIV testing, risk reduction counselling, receive HIV test results
Show all 10Show fewer
- All sexually active males (unless anatomically sterile or in a monogamous relationship with a female partner who uses a documented non-barrier method of birth control) must be willing to use an effective method of contraception (such as consistent condom use) from the day of first vaccination until 4 months after the last vaccination.
- If a female of childbearing potential, willing to use an effective non-barrier method of contraception (hormonal contraceptive or intrauterine device) from at least 2 weeks prior to first vaccination until at least 4 months after the last study vaccination. If not of childbearing potential: postmenopausal (>45 years of age with amenorrhea for at least 2 years, or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level >40 IU/L) or surgically sterile: no additional contraception required.
- All female volunteers must be willing to undergo urine pregnancy tests at time points indicated in the Schedule of Procedures and must test negative prior to each study vaccination.
- Willing to forego donations of blood or any other tissues during the trial and, for those who test positive for HIV antibodies due to vaccination (vaccine-induced seropositivity/ reactivity), until the anti-HIV antibody titres become undetectable.
Who cannot join
- Confirmed HIV-1 or HIV-2 infection
- Receipt of any vaccine in the previous 28 days or planned receipt within 28 days of Investigational Medicinal Product. Volunteers who expect to receive any adenoviral vectored vaccines within the next three months after ChAdOx1.tHIVconsv1 vaccine administration should not participate due to the risk of immune interference with the study vaccine.
- Participation in another clinical trial of an Investigational Medicinal Product (IMP) currently, within the previous 3 months or expected participation during the study.
- Receipt of another investigational HIV vaccine candidate or investigational adenoviral vectored vaccine (Note: receipt of an HIV vaccine placebo will not exclude a volunteer from participation if documentation is available and the Medical Monitor gives approval).
- Receipt of blood transfusion or blood-derived products within the previous 4 months or expectation of receiving blood products during the study period.
- Receipt of immunoglobulin products within the previous 3 months.
Show all 39Show fewer
- If female, pregnant or planning a pregnancy during the period of enrolment until 4 months after the last study vaccination; or lactating.
- Any clinically relevant abnormality on history or examination such as:
- Any confirmed or suspected history of immunodeficiency including recurrent severe infections;
- Use of systemic corticosteroids for >14 days (use of topical or inhaled steroids is permitted) within the previous 6 months;
- Immunosuppressive, anti-cancer, anti-tuberculosis or other medications considered significant by the investigator within the previous 6 months.
- History of splenectomy.
- History of autoimmune disease
- Bleeding disorder diagnosed by a physician (e.g., factor deficiency, coagulopathy or platelet disorder that requires special precautions). (Note: a volunteer that states that he or she has easy bruising or bleeding but does not have a formal diagnosis and has intramuscular injections and blood draws without any adverse experience is eligible)
- History of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with permanent sequelae, or clinically significant arrhythmia (including any arrhythmia requiring medication, treatment, or clinical follow up).
- History of cancer (except basal cell carcinoma of the skin)
- Asthma that is not well controlled.
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine
- History of severe local or systemic reactogenicity to vaccines (e.g., anaphylaxis, respiratory difficulty, angioedema).
- History of Guillain-Barre syndrome.
- Confirmed diagnosis of active or chronic hepatitis B, hepatitis C, active syphilis and/or active tuberculosis
- Seizure disorder: an individual who has had a seizure in the last 3 years is excluded (Not excluded: an individual with a history of seizures who has neither required medication nor had a seizure for three or more years).
- History of serious psychiatric conditions or any psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
- Substance abuse disorder that precludes compliance with the protocol as assessed by the investigator.
- Any clinically significant acute or chronic medical condition that is considered unstable/progressive, or in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer's ability to participate in the study
- Abnormal clinically significant abnormal finding on screening biochemistry or haematology blood, or urinalysis, including but not limited to:
- Haematology:
- Haemoglobin - <9.5 g/dl in females; <11.0 g/dl in males
- Absolute Neutrophil Count (ANC) - ≤1,000/mm3
- Absolute Lymphocyte Count (ALC) - ≤650/mm3
- Platelets - <100,000 cells/mm3 Chemistry
- Creatinine >1.1 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) >1.25 x ULN
- Alanine aminotransferase (ALT) >1.25 x ULN Urinalysis
- Clinically significant abnormal dipstick confirmed by microscopy:
- Protein = 2+ or more
- Blood = 2+ or more (not due to menses)
- Any other finding which in the opinion of the investigators would significantly increase the risk of having an adverse outcome from participating in the study
- If, in the opinion of the Principal Investigator, it is not in the best interest of the volunteer to participate in the trial.
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
Kenya2 sites
Kenya Medical Research Institute Wellcome Trust Programme
Kilifi, PO Box 230, 80108
Kenya AIDS Vaccine Institute for Clinical Research
Nairobi, PO Box 19676-00202
Uganda1 site
Medical Research and Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit
Masaka
About this study
Official title: A Phase 1 Trial of ChAdOx1- and MVA-vectored Conserved Mosaic HIV-1 Vaccines in Healthy, Adult HIV-1-negative Volunteers in Eastern and Southern Africa.
HIV-CORE 006 is a Phase 1 double-blind placebo-controlled trial, in which the mosaic immunogens are delivered by a prime-boost regimen of non-replicating simian adenovirus followed by non-replicating poxvirus MVA. Volunteers will be randomised to receive either the vaccine regimen or placebo at 2 vaccination visits 4 weeks apart. The vaccine regimen consists of a single mosaic prime ChAdOx1.tHIVconsv1 (C1) and a dual boost of MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) administered simultaneously. The trial will recruit healthy African adults 18-50 years of age, who are HIV-uninfected and at low risk of HIV infection.
The trial is designed to enrol 88 healthy men and women, who will be randomised to receive either the vaccine regimen or placebo in a ratio of 72:16:
Read more
- Vaccine Arm (ChAdOx1.tHIVconsv1 prime followed by MVA.tHIVconsv3 and MVA.tHIVconsv4 boost at 4 weeks after enrolment); 72 vaccine recipients;
- Placebo Arm; 16 recipients
To maintain blinding, all volunteers will receive two injections with half dose into the deltoid region of each arm of ChAdOx1.tHIVconsv1 or placebo at enrolment, and two injections (MVA.tHIVconsv3 or placebo into one deltoid region and MVA.tHIVconsv4 or placebo into the other) at 4 weeks after enrolment. The primary goal of assessing safety and immunogenicity will be served by weighting the randomisation toward vaccinees.
Read the detailed description
Phase 1 clinical trial HIV-CORE (COnserved REgions) 006 is a trial of a new combined vaccine regimen to determine safety and immunogenicity in healthy adults in Kenya, Uganda and Zambia. Immune responses may vary between populations and so it is important to confirm that the vaccines are suitable for the people and environment where they will be deployed for protection against HIV/AIDS. There are many different strains of HIV-1, and the virus can change to escape immune responses. This vaccine regimen is designed to work in all parts of the world.
The aim is to induce effective cytotoxic T lymphocytes (CTL) against HIV-1. These could complement broadly neutralizing antibodies in prophylaxis and play a central role in cure. CTL exert their effector functions by killing HIV-1-infected cells and producing soluble factors, which directly or indirectly counteract the HIV-1 replicative cycle. In future, this approach could be combined, in human efficacy testing, with other immunogens that stimulate humoral responses, with the goal of effectively preventing HIV-1 infections.
The central principle of this strategy is to focus T-cell immune responses on the most conserved regions of the HIV-1 proteome. These regions are common to most variants and, if mutated, reduce the ability of the virus to grow; these regions are the "Achilles heel" of HIV-1. Targeting of conserved regions is further enhanced by using 'mosaic' proteins, which are designed by computer to maximize the match of the vaccine with global HIV-1 variants and to block common ways the HIV-1 changes to escape the immune response. Vaccines should match circulating HIV-1 variants as much as possible to stop them efficiently. When T cells attack conserved parts of HIV-1 proteins (parts that seldom or never change), the disease is better controlled-this vaccine includes those parts.
The HIV-1-derived mosaic genes are called tHIVconsvX and are delivered by two safe, non-replicating vaccine vectors derived from chimpanzee adenovirus and poxvirus modified vaccinia virus Ankara (MVA). Adenoviruses, if able to grow, normally cause respiratory and gastrointestinal ailments, while the unmodified chimpanzee adenovirus is not known to cause disease in humans; the engineered vaccine vector called ChAdOx1 is crippled so it cannot grow. ChAdOx1 and similar experimental vaccines have been shown to be safe in over 1,500 human volunteers. MVA is a poxvirus, which does not replicate in humans. It was used safely as the smallpox vaccine in over 120,000 people at the end of the smallpox-eradication campaign and as an experimental vaccine vector against a variety of diseases in many clinical trials.
Humans and microbiota, which consist of bacteria, fungi, viruses and eukaryotic species, have co-evolved over millions of years and their coexistence is beneficial to both parties. Human immune system is constitutively exposed to microbial stimulation and any vaccine design and responsiveness needs to be considered in the context of host-microbiota interactions. Manipulation of the microbiota functions and composition through diet, engraftment and/or any other means may thus become a viable strategy for improving vaccine responsiveness as well as treating malfunctions of the immune system. The first reports on the influence of gut microbiota diversity and composition on responses to vaccination have been emerging for some time. As part of the exploratory endpoints for this trial, the gut microbiome of study volunteers will be characterised for composition and richness before and after administration of the study vaccines.
The ChAdOx1-vectored HIV-1 vaccine in this trial will be tested for the first time in humans, and MVA.tHIVconsv3 and MVA.tHIVconsv4 (M3M4) are currently administered to HIV-positive individuals in the first-in-human clinical trial in the USA (NCT03844386). However, this is the first time these C1-M3M4 vaccines will be administered to humans sequentially. In parallel with HIV-CORE 006, these vaccines will be tested for safety in the United Kingdom, in a phase I trial HIV-CORE 0052. The tHIVconsvX vaccines have been designed for global use irrespective of the HIV-1 strain and are therefore very suitable for Africa, where multiple strains are responsible for the epidemic, mainly from the HIV-1 families A, D and C. The HIV-CORE 006 trial will take place at four sites in Africa and will enrol healthy adults between 18 and 50 years of age. It is not yet known whether the vaccine will have a beneficial effect, no effect, or whether it could cause harm. The health of trial volunteers will be monitored carefully, and volunteers will receive counselling and support to minimise HIV-1 infection.
This trial is funded by EDCTP, under the SRIA-2015-1066 grant
- Conditions
- HIV-1-infection
- Being tested
- Vaccine, Placebo
- Keywords
- HIV, vaccine, adenovirus, poxvirus, ChAdOx1, MVA
- Medical subject headings
- Adenoviridae Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VaccineBiological
IM vaccination with ChAdOx1.tHIVconsv1, MVA.tHIVconsv3 and MVA.tHIVconsv4
PlaceboBiological
IM administration of 0.9% sterile sodium chloride solution
| Study group | Role | What they receive |
|---|---|---|
| 1: Vaccine | Experimental | At Week 0, volunteers receive 5.0 x 10^10 virus particles (vp) of ChAdOx1.tHIVconsv1 (C1) administered intramuscularly (IM). The dose is divided in 2 and administered in the deltoid muscle of each arm.
At week 4,1.0 x 10^8 Plaque forming units (PFU) of MVA.tHIVconsv3 (M3) administered IM and 0.9 x 10^8 PFU of MVA.tHIVconsv4 (M4) are administered IM simultaneously, one into the deltoid muscle of each arm. Receives: Biological: Vaccine |
| 2. Placebo | Placebo comparator | Normal sterile saline (0.9% Sodium Chloride solution) administered IM as Placebo, the volume is matched to that of the vaccines and administered in the deltoid muscle of each arm at Week 0 and at week 4 . Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety- local and systemic reactogenicity post vaccination
Proportion of volunteers with local and systemic reactogenicity events from Day 0 to Day 7 post vaccination
Measured: 7 days
Safety - unsolicited Grade 3 or Grade 4 adverse events post vaccination
Proportion of volunteers with Grade 3 or 4 unsolicited adverse events through 28 days post final vaccination
Measured: 28 days
Safety - vaccine related SAEs
Proportion of volunteers with vaccine related serious adverse events (SAEs) collected throughout the study period
Measured: 48 weeks
Immunogenicity - HIV-1 specific T-cell responses
Proportion of vaccine recipients developing HIV-1-specific T-cell responses
Measured: 44 weeks
Secondary outcomes (2)
Immunogenicity- Analysis of T-cell responses
Frequency, breadth and duration of T-cell responses to conserved epitopes measured by interferon-gamma ELISPOT assay in each vaccine recipient
Measured: 44 weeks
Immunogenicity- Inhibition of HIV-1 viruses
Breadth of inhibition of HIV-1 viruses representative of circulating viruses in Kenya, Uganda and Zambia and other global clades in the in vitro Virus Inhibition Assay
Measured: 44 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2020
- Study start16 Aug 2021
- Primary completionNov 2022 (estimated)
- Study completionNov 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double-blind placebo-controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP), University of Nairobi, KEMRI-Wellcome Trust Collaborative Research Program, London School of Hygiene and Tropical Medicine, International AIDS Vaccine Initiative, Imperial College London, Center for Family Health Research in Zambia
- Responsible party
- Sponsor
- Investigators
- Walter Jaoko, MD, Principal investigator, University of NairobiPontiano Kaleebu, MD, Principal investigator, London School of Hygiene and Tropical MedicineWilliam Kilembe, MD, Principal investigator, Center for Family Health Research in ZambiaEduard Sanders, MD, Principal investigator, KEMRI-Wellcome TrustPaola Cicconi, MD, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04553016
- Sponsor's protocol ID
- HIV-CORE 006
- Acronym
- HIV-CORE 006
- Status last verified
- Jun 2022
- First submitted
- 10 Sep 2020
- Last updated
- 22 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study information will be made available through an open repository. The information to be made available will be anonymized so that there is no link to participants and will include data on safety, immune responses and any other data generated from samples obtained in this study.
Publications
Chanda C, Kibengo F, Mutua M, Ogada F, Muturi-Kioi V, Akis Yildirim BM, Amondi M, Baines A, Basajja V, Borthwick N, Bosire K, Chambula E, Chetty P, Chinyenze K, Chirro O, Crook A, De Bont J, Fernandez N, Ejou P, Farah B, Glaze M, Gombe B, Gumbe A, Hayes P, Itwi S, Juma S, Kabarambi A, Kabengele C, Kafeero P, Kakande A, Kanungi J, Kidega W, King D, Mahira R, Malogo R, Matsoso M, Michelo C, Moyo A, Mugaba S, Mugenya I, Muhumuza P, Mujadidi YF, Muriuki M, Musale V, Mutua G, Muwowo M, Mwale F, Mwangi I, Nakimbugwe M, Namuyanja A, Nduati E, Nielsen L, Nyange J, Oino G, Okech B, Omosa-Manyonyi G, Otieno D, Palmer S, Phiri H, Ramko K, Rutishauser RL, Sayeed E, Sajabi R, Serwanga J, G-T Wee E, Wenden C, Cicconi P, Fast P, Gilmour J, Jaoko W, Kaleebu P, Kilembe W, Kuipers H, Sanders EJ, Hanke T. Safety and broad immunogenicity of HIVconsvX conserved mosaic candidate T-cell vaccines vectored by ChAdOx1 and MVA in HIV-CORE 006: a double-blind, randomised, placebo-controlled phase 1 trial in healthy adults living without HIV-1 in eastern and southern Africa. Lancet Microbe. 2025 Jun;6(6):101041. doi: 10.1016/j.lanmic.2024.101041. Epub 2025 May 16.
PubMed 40388952
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Trial of ChAdOx1- and MVA-vectored Conserved Mosaic HIV-1 Vaccines in Healthy, Adult HIV-1-negative Volunteers in Eastern and Southern Africa.
- ClinicalTrials.gov ID
- NCT04553016
- Acronym / sponsor ID
- HIV-CORE 006 / HIV-CORE 006
- Conditions
- HIV-1-infection
- Keywords
- HIV, vaccine, adenovirus, poxvirus, ChAdOx1, MVA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 88 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP), University of Nairobi, KEMRI-Wellcome Trust Collaborative Research Program, London School of Hygiene and Tropical Medicine, International AIDS Vaccine Initiative, Imperial College London, Center for Family Health Research in Zambia
- Study start
- 16 Aug 2021 (actual)
- Primary completion
- Nov 2022 (estimated)
- Study completion
- Nov 2022 (estimated)
- First posted
- 17 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
HIV-CORE 006 is a Phase 1 double-blind placebo-controlled trial, in which the mosaic immunogens are delivered by a prime-boost regimen of non-replicating simian adenovirus followed by non-replicating poxvirus MVA. Volunteers will be randomised to receive either the vaccine regimen or placebo at 2 vaccination visits 4 weeks apart. The vaccine regimen consists of a single mosaic prime ChAdOx1.tHIVconsv1 (C1) and a dual boost of MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) administered simultaneously. The trial will recruit healthy African adults 18-50 years of age, who are HIV-uninfected and at low risk of HIV infection.
The trial is designed to enrol 88 healthy men and women, who will be randomised to receive either the vaccine regimen or placebo in a ratio of 72:16:
- Vaccine Arm (ChAdOx1.tHIVconsv1 prime followed by MVA.tHIVconsv3 and MVA.tHIVconsv4 boost at 4 weeks after enrolment); 72 vaccine recipients;
- Placebo Arm; 16 recipients
To maintain blinding, all volunteers will receive two injections with half dose into the deltoid region of each arm of ChAdOx1.tHIVconsv1 or placebo at enrolment, and two injections (MVA.tHIVconsv3 or placebo into one deltoid region and MVA.tHIVconsv4 or placebo into the other) at 4 weeks after enrolment. The primary goal of assessing safety and immunogenicity will be served by weighting the randomisation toward vaccinees.
Detailed description
Phase 1 clinical trial HIV-CORE (COnserved REgions) 006 is a trial of a new combined vaccine regimen to determine safety and immunogenicity in healthy adults in Kenya, Uganda and Zambia. Immune responses may vary between populations and so it is important to confirm that the vaccines are suitable for the people and environment where they will be deployed for protection against HIV/AIDS. There are many different strains of HIV-1, and the virus can change to escape immune responses. This vaccine regimen is designed to work in all parts of the world.
The aim is to induce effective cytotoxic T lymphocytes (CTL) against HIV-1. These could complement broadly neutralizing antibodies in prophylaxis and play a central role in cure. CTL exert their effector functions by killing HIV-1-infected cells and producing soluble factors, which directly or indirectly counteract the HIV-1 replicative cycle. In future, this approach could be combined, in human efficacy testing, with other immunogens that stimulate humoral responses, with the goal of effectively preventing HIV-1 infections.
The central principle of this strategy is to focus T-cell immune responses on the most conserved regions of the HIV-1 proteome. These regions are common to most variants and, if mutated, reduce the ability of the virus to grow; these regions are the "Achilles heel" of HIV-1. Targeting of conserved regions is further enhanced by using 'mosaic' proteins, which are designed by computer to maximize the match of the vaccine with global HIV-1 variants and to block common ways the HIV-1 changes to escape the immune response. Vaccines should match circulating HIV-1 variants as much as possible to stop them efficiently. When T cells attack conserved parts of HIV-1 proteins (parts that seldom or never change), the disease is better controlled-this vaccine includes those parts.
The HIV-1-derived mosaic genes are called tHIVconsvX and are delivered by two safe, non-replicating vaccine vectors derived from chimpanzee adenovirus and poxvirus modified vaccinia virus Ankara (MVA). Adenoviruses, if able to grow, normally cause respiratory and gastrointestinal ailments, while the unmodified chimpanzee adenovirus is not known to cause disease in humans; the engineered vaccine vector called ChAdOx1 is crippled so it cannot grow. ChAdOx1 and similar experimental vaccines have been shown to be safe in over 1,500 human volunteers. MVA is a poxvirus, which does not replicate in humans. It was used safely as the smallpox vaccine in over 120,000 people at the end of the smallpox-eradication campaign and as an experimental vaccine vector against a variety of diseases in many clinical trials.
Humans and microbiota, which consist of bacteria, fungi, viruses and eukaryotic species, have co-evolved over millions of years and their coexistence is beneficial to both parties. Human immune system is constitutively exposed to microbial stimulation and any vaccine design and responsiveness needs to be considered in the context of host-microbiota interactions. Manipulation of the microbiota functions and composition through diet, engraftment and/or any other means may thus become a viable strategy for improving vaccine responsiveness as well as treating malfunctions of the immune system. The first reports on the influence of gut microbiota diversity and composition on responses to vaccination have been emerging for some time. As part of the exploratory endpoints for this trial, the gut microbiome of study volunteers will be characterised for composition and richness before and after administration of the study vaccines.
The ChAdOx1-vectored HIV-1 vaccine in this trial will be tested for the first time in humans, and MVA.tHIVconsv3 and MVA.tHIVconsv4 (M3M4) are currently administered to HIV-positive individuals in the first-in-human clinical trial in the USA (NCT03844386). However, this is the first time these C1-M3M4 vaccines will be administered to humans sequentially. In parallel with HIV-CORE 006, these vaccines will be tested for safety in the United Kingdom, in a phase I trial HIV-CORE 0052. The tHIVconsvX vaccines have been designed for global use irrespective of the HIV-1 strain and are therefore very suitable for Africa, where multiple strains are responsible for the epidemic, mainly from the HIV-1 families A, D and C. The HIV-CORE 006 trial will take place at four sites in Africa and will enrol healthy adults between 18 and 50 years of age. It is not yet known whether the vaccine will have a beneficial effect, no effect, or whether it could cause harm. The health of trial volunteers will be monitored carefully, and volunteers will receive counselling and support to minimise HIV-1 infection.
This trial is funded by EDCTP, under the SRIA-2015-1066 grant
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- double-blind placebo-controlled
| Arm | Type | Receives |
|---|---|---|
| 1: Vaccine | Experimental | Biological: VaccineAt Week 0, volunteers receive 5.0 x 10^10 virus particles (vp) of ChAdOx1.tHIVconsv1 (C1) administered intramuscularly (IM). The dose is divided in 2 and administered in the deltoid muscle of each arm. At week 4,1.0 x 10^8 Plaque forming units (PFU) of MVA.tHIVconsv3 (M3) administered IM and 0.9 x 10^8 PFU of MVA.tHIVconsv4 (M4) are administered IM simultaneously, one into the deltoid muscle of each arm. |
| 2. Placebo | Placebo comparator | Biological: PlaceboNormal sterile saline (0.9% Sodium Chloride solution) administered IM as Placebo, the volume is matched to that of the vaccines and administered in the deltoid muscle of each arm at Week 0 and at week 4 . |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Healthy male and female as assessed by a medical history, physical exam, and laboratory tests.
- At low risk of HIV infection and willing to maintain low-risk behaviour for the duration of the trial. Individuals from key populations are not excluded provided they are assessed to be at low risk of HIV infection at screening and are willing to maintain low-risk behaviour during the study.
- At least 18 years of age on the day of screening and have not reached their 51st birthday on the day of the first vaccination.
- Willing and able to give informed consent for participation in the trial before any study-related procedures are performed. Volunteers will pass an Assessment of Understanding before signing the consent form.
- Willing to comply with the requirements of the protocol and be available for follow up for the planned duration of the study.
Key exclusion criteria (39 listed)
- Confirmed HIV-1 or HIV-2 infection
- Receipt of any vaccine in the previous 28 days or planned receipt within 28 days of Investigational Medicinal Product. Volunteers who expect to receive any adenoviral vectored vaccines within the next three months after ChAdOx1.tHIVconsv1 vaccine administration should not participate due to the risk of immune interference with the study vaccine.
- Participation in another clinical trial of an Investigational Medicinal Product (IMP) currently, within the previous 3 months or expected participation during the study.
- Receipt of another investigational HIV vaccine candidate or investigational adenoviral vectored vaccine (Note: receipt of an HIV vaccine placebo will not exclude a volunteer from participation if documentation is available and the Medical Monitor gives approval).
- Receipt of blood transfusion or blood-derived products within the previous 4 months or expectation of receiving blood products during the study period.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VaccineIM vaccination with ChAdOx1.tHIVconsv1, MVA.tHIVconsv3 and MVA.tHIVconsv4 | Biological | 1: Vaccine |
| PlaceboIM administration of 0.9% sterile sodium chloride solution | Biological | 2. Placebo |
Primary outcome
Safety- local and systemic reactogenicity post vaccination
Time frame: 7 days
Proportion of volunteers with local and systemic reactogenicity events from Day 0 to Day 7 post vaccination
Safety - unsolicited Grade 3 or Grade 4 adverse events post vaccination
Time frame: 28 days
Proportion of volunteers with Grade 3 or 4 unsolicited adverse events through 28 days post final vaccination
Safety - vaccine related SAEs
Time frame: 48 weeks
Proportion of volunteers with vaccine related serious adverse events (SAEs) collected throughout the study period
Immunogenicity - HIV-1 specific T-cell responses
Time frame: 44 weeks
Proportion of vaccine recipients developing HIV-1-specific T-cell responses
2 secondary outcomes
Immunogenicity- Analysis of T-cell responses
Time frame: 44 weeks
Immunogenicity- Inhibition of HIV-1 viruses
Time frame: 44 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2022.
- Derived from this study: PubMed 40388952Chanda C, Kibengo F, Mutua M, Ogada F, Muturi-Kioi V, Akis Yildirim BM, Amondi M, Baines A, Basajja V, Borthwick N, Bosire K, Chambula E, Chetty P, Chinyenze K, Chirro O, Crook A, De Bont J, Fernandez N, Ejou P, Farah B, Glaze M, Gombe B, Gumbe A, Hayes P, Itwi S, Juma S, Kabarambi A, Kabengele C, Kafeero P, Kakande A, Kanungi J, Kidega W, King D, Mahira R, Malogo R, Matsoso M, Michelo C, Moyo A, Mugaba S, Mugenya I, Muhumuza P, Mujadidi YF, Muriuki M, Musale V, Mutua G, Muwowo M, Mwale F, Mwangi I, Nakimbugwe M, Namuyanja A, Nduati E, Nielsen L, Nyange J, Oino G, Okech B, Omosa-Manyonyi G, Otieno D, Palmer S, Phiri H, Ramko K, Rutishauser RL, Sayeed E, Sajabi R, Serwanga J, G-T Wee E, Wenden C, Cicconi P, Fast P, Gilmour J, Jaoko W, Kaleebu P, Kilembe W, Kuipers H, Sanders EJ, Hanke T. Safety and broad immunogenicity of HIVconsvX conserved mosaic candidate T-cell vaccines vectored by ChAdOx1 and MVA in HIV-CORE 006: a double-blind, randomised, placebo-controlled phase 1 trial in healthy adults living without HIV-1 in eastern and southern Africa. Lancet Microbe. 2025 Jun;6(6):101041. doi: 10.1016/j.lanmic.2024.101041. Epub 2025 May 16.
- Individual participant dataSharing planned: Yes. Study information will be made available through an open repository. The information to be made available will be anonymized so that there is no link to participants and will include data on safety, immune responses and any other data generated from samples obtained in this study.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Walter Jaoko, MD principal investigator
University of Nairobi
Pontiano Kaleebu, MD principal investigator
London School of Hygiene and Tropical Medicine
William Kilembe, MD principal investigator
Center for Family Health Research in Zambia
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vaccine in people with HIV-1-infection, run by University of Oxford at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Kenya, Uganda, Zambia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety- local and systemic reactogenicity post vaccination (time frame: 7 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04553016, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2022.