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A Study to Test Three Experimental HIV Vaccines in Healthy Adults. (HIV-CORE 006)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04553016
Recruitment Status : Recruiting
First Posted : September 17, 2020
Last Update Posted : October 11, 2021
Sponsor:
Collaborators:
European and Developing Countries Clinical Trials Partnership (EDCTP)
University of Nairobi
KEMRI-Wellcome Trust Collaborative Research Program
MRC/UVRI & LSHTM Uganda Research Unit
International AIDS Vaccine Initiative
Imperial College London
Center for Family Health Research in Zambia
Information provided by (Responsible Party):
University of Oxford

Brief 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. 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.


Condition or disease Intervention/treatment Phase
HIV-1-infection Biological: Vaccine Biological: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 88 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: double-blind placebo-controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

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.

Unblinded study pharmacist(s) staff at each site will be responsible for investigational medicinal product preparation and accountability. All other site staff and all trial volunteers will be blinded to treatment assignment (i.e., active versus placebo).

Primary Purpose: Prevention
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.
Actual Study Start Date : August 16, 2021
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Vaccines

Arm Intervention/treatment
Experimental: 1: Vaccine

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.

Biological: Vaccine
IM vaccination with ChAdOx1.tHIVconsv1, MVA.tHIVconsv3 and MVA.tHIVconsv4

Placebo Comparator: 2. Placebo
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 .
Biological: Placebo
IM administration of 0.9% sterile sodium chloride solution




Primary Outcome Measures :
  1. 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

  2. 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

  3. Safety - vaccine related SAEs [ Time Frame: 48 weeks ]
    Proportion of volunteers with vaccine related serious adverse events (SAEs) collected throughout the study period

  4. Immunogenicity - HIV-1 specific T-cell responses [ Time Frame: 44 weeks ]
    Proportion of vaccine recipients developing HIV-1-specific T-cell responses


Secondary Outcome Measures :
  1. Immunogenicity- Analysis of T-cell responses [ Time Frame: 44 weeks ]
    Frequency, breadth and duration of T-cell responses to conserved epitopes measured by interferon-gamma ELISPOT assay in each vaccine recipient

  2. Immunogenicity- Inhibition of HIV-1 viruses [ Time Frame: 44 weeks ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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
  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04553016


Contacts
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Contact: Paola Cicconi, MD +44 (0) 1865 611413 paola.cicconi@ndm.ox.ac.uk
Contact: Alison Crook, PhD +44 (0)1865 611421 alison.crook@ndm.ox.ac.uk

Locations
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Kenya
Kenya Medical Research Institute Wellcome Trust Programme Recruiting
Kilifi, Kenya, PO Box 230, 80108
Contact: Clara A Agutu, MBChB    +254720735000    cagutu@kemri-wellcome.org   
Contact: Fred W Ogada, Dip    +254724894643    FOgada@kemri-wellcome.org   
Kenya AIDS Vaccine Institute for Clinical Research Recruiting
Nairobi, Kenya, PO Box 19676-00202
Contact: Gaudensia Mutua, MD    +254733826815    gmutua@kaviuon.org   
Uganda
Medical Research and Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit Not yet recruiting
Masaka, Uganda
Contact: Pontiano Kaleebu, MD    +256 417704103    pontiono.kaleebu@mrcuganda.org   
Contact: Freddie Makasa Kibengo, MD    +256772435251    Freddie.Kibengo@mrcuganda.org   
Zambia
Center for Family Health Research in Zambia Recruiting
Lusaka, Zambia, 10101
Contact: William Kilembe, MD    +260966862787    wkilembe@rzhrg-mail.org   
Contact: Tyronza Sharkey    +260966862037    tsharkey@rzhg-mail.org   
Sponsors and Collaborators
University of Oxford
European and Developing Countries Clinical Trials Partnership (EDCTP)
University of Nairobi
KEMRI-Wellcome Trust Collaborative Research Program
MRC/UVRI & LSHTM Uganda Research Unit
International AIDS Vaccine Initiative
Imperial College London
Center for Family Health Research in Zambia
Investigators
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Principal Investigator: Walter Jaoko, MD University of Nairobi
Principal Investigator: Pontiano Kaleebu, MD MRC/UVRI & LSHTM Uganda Research Unit
Principal Investigator: William Kilembe, MD Center for Family Health Research in Zambia
Principal Investigator: Eduard Sanders, MD KEMRI-Wellcome Trust
Principal Investigator: Paola Cicconi, MD University of Oxford
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Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT04553016    
Other Study ID Numbers: HIV-CORE 006
First Posted: September 17, 2020    Key Record Dates
Last Update Posted: October 11, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Time Frame: Within 12 months of the study completion date we will provide the additional document types as described above.
Access Criteria: Aim is to provide a summary of the results or a link to summary results within the trial registration record.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Oxford:
HIV
vaccine
adenovirus
poxvirus
ChAdOx1
MVA