A Study to Test Three Experimental HIV Vaccines in Healthy Adults.

NCT04553016 | Unknown Phase 1 DMC

• 1 other identifier: HIV-CORE 006
• Study Type: interventional
• Target: 88
• Locations: 3 countries
• Sites: 4

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.

Conditions

HIV-1-infection

Keywords

HIV; vaccine; adenovirus; poxvirus; ChAdOx1; MVA

Outcome Measures

Primary Outcomes (4)

• Safety- local and systemic reactogenicity post vaccination

  Proportion of volunteers with local and systemic reactogenicity events from Day 0 to Day 7 post vaccination

  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

  28 days

• Safety - vaccine related SAEs

  Proportion of volunteers with vaccine related serious adverse events (SAEs) collected throughout the study period

  48 weeks

• Immunogenicity - HIV-1 specific T-cell responses

  Proportion of vaccine recipients developing HIV-1-specific T-cell responses

  44 weeks

Secondary Outcomes (2)

• Immunogenicity- Analysis of T-cell responses

  44 weeks

• Immunogenicity- Inhibition of HIV-1 viruses

  44 weeks

Study Arms (2)

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.

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 .

Biological: Placebo

Interventions

Vaccine BIOLOGICAL

IM vaccination with ChAdOx1.tHIVconsv1, MVA.tHIVconsv3 and MVA.tHIVconsv4

1: Vaccine

Placebo BIOLOGICAL

IM administration of 0.9% sterile sodium chloride solution

2. Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Oxford: lead
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator
• University of Nairobi: collaborator
• KEMRI-Wellcome Trust Collaborative Research Program: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• International AIDS Vaccine Initiative: collaborator
• Imperial College London: collaborator
• Center for Family Health Research in Zambia: collaborator

Study Sites (4)

Kenya Medical Research Institute Wellcome Trust Programme

Kilifi, PO Box 230, 80108, Kenya

Location

Kenya AIDS Vaccine Institute for Clinical Research

Nairobi, PO Box 19676-00202, Kenya

Location

Medical Research and Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit

Masaka, Uganda

Location

Center for Family Health Research in Zambia

Lusaka, 10101, Zambia

Location

Related Publications (1)

• 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.

  PMID: 40388952 DERIVED

MeSH Terms

Conditions

Adenoviridae Infections

Interventions

Vaccines

Condition Hierarchy (Ancestors)

DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• Walter Jaoko, MD

  University of Nairobi

  PRINCIPAL INVESTIGATOR

• Pontiano Kaleebu, MD

  London School of Hygiene and Tropical Medicine

  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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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).
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: double-blind placebo-controlled

Study Record Dates

• First Submitted: September 10, 2020
• First Posted: September 17, 2020
• Study Start: August 16, 2021
• Primary Completion: November 1, 2022
• Study Completion: November 1, 2022
• Last Updated: June 22, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: 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.

Locations

KE (2); ZA (1); UG (1)