Combination Vaccination and Broadly Neutralising Antibody Therapy in HIV

NCT07054931 | Recruiting Phase 2 DMC

• 2 other identifiers: AbVaxMR/Y008847/1
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 3

Brief Summary

There is no cure for HIV infection. Antiretroviral therapy (ART) is widely available but requires daily, life-long intake. This can cause issues around side-effects, resistance, adherence and stigma. A new therapy, broadly neutralising antibodies, (bNAbs), may work as well as ART and may last longer - one dose can last six months. bNAbs appear to first target HIV viruses, then drive a protective immune response conferring long-term control, called the vaccinal effect. AbVax is a clinical trial to understand this effect and how to enhance it to give the strongest possible long-term protection for people living with HIV (PWH). The investigators are studying whether a combination of vaccines that attack HIV, a short period of treatment interruption induced viraemia (TIIV - stopping ART for a few weeks to allow a small amount of virus to return to the bloodstream) and bNABs will produce the most sustained immune protection.

Conditions

HIV

Keywords

vaccination; broadly neutralising antibodies; HIV treatment

Outcome Measures

Primary Outcomes (1)

• Fold change in T cell immune response to the HIV Gag protein

  The geometric mean of the fold-change (GMFC) will be compared between Arm C compared to Arm A; and Arm C compared to Arm B.

  Baseline and 12 weeks after ATI

Secondary Outcomes (11)

• Safety Assessment

  From enrollment until 16 weeks after restarting ART after ATI

• Safety Assessment

  From enrollment until 16 weeks after ART restart after ATI

• HIV viral control

  Weeks 12 and weeks 24 after ATI

• Immunological correlation of virological remission

  Week 12 and week 24 after ATI

• Immunological correlates of virological remission

  Weeks 12 and 24 after ATI

Study Arms (3)

Arm A

ACTIVE COMPARATOR

Participants in Arm A will undergo a period of treatment interruption induced viraemia followed by two infusions of broadly neutralising antibodies (GS-5423 and GS-2872). They will then stop ART for an analytical treatment interruption period to determine the clinical impact and to measure how long before any HIV virus returns to the blood.

Biological: GS-5423; Biological: GS-2872; Other: Treatment interruption induced viraemia

Arm B

ACTIVE COMPARATOR

Participants in Arm B will receive a combination of three HIV vaccines (one prime dose (ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62) followed by two booster doses of MVA.tHIVconsv4 at 4 weeks and 16 weeks), followed by two infusions of broadly neutralising antibodies, GS-5423 and GS-2872. They will then stop ART for an analytical treatment interruption period to determine the clinical impact and to measure how long before any HIV virus returns to the blood.

Biological: ChAdOx1.tHIVconsv1; Biological: ChAdOx1.HIVconsv62; Biological: MVA.tHIVconsv4; Biological: GS-5423; Biological: GS-2872

Arm C

ACTIVE COMPARATOR

Participants in Arm C will undergo a period of treatment interruption induced viraemia followed by a combination of three HIV vaccines (one prime dose (ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62) followed by two booster doses of MVA.tHIVconsv4 at 4 weeks and 16 weeks), followed by two infusions of broadly neutralising antibodies, GS-5423 and GS-2872. They will then stop ART for an analytical treatment interruption period to determine the clinical impact and to measure how long before any HIV virus returns to the blood.

Biological: ChAdOx1.tHIVconsv1; Biological: ChAdOx1.HIVconsv62; Biological: MVA.tHIVconsv4; Biological: GS-5423; Biological: GS-2872; Other: Treatment interruption induced viraemia

Interventions

ChAdOx1.tHIVconsv1 BIOLOGICAL

solution for injection one dose of 2.5 x 10\^10 vp/ml Arm B and Arm C

Arm B; Arm C

ChAdOx1.HIVconsv62 BIOLOGICAL

solution for injection one dose of 2.5 x 10\^10 vp/ml Arm B and Arm C

Arm B; Arm C

MVA.tHIVconsv4 BIOLOGICAL

suspension for injection two doses of 1 x 10\^8 vpu/ml Arm B and Arm C

Arm B; Arm C

GS-5423 BIOLOGICAL

Solution for infusion 2550 mg Arm A, Arm B and Arm C

Arm A; Arm B; Arm C

GS-2872 BIOLOGICAL

Solution for infusion 850 mg Arm A, Arm B and Arm C

Arm A; Arm B; Arm C

Treatment interruption induced viraemia OTHER

Participants pause ART before receiving vaccines and/or bNAbs Arm A and Arm C

Arm A; Arm C

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• PWH aged ≥18 to ≤64 years old at screening
• Able to give informed written consent including consent to long-term follow-up
• Willing and able to comply with visit schedule and provide blood sampling
• Willing to consent to their HIV care team being informed of their participation and sharing relevant clinical information
• Stable on oral ART with suppressed undetectable HIV pVL 'target not detected' (TND) using local assays for ≥ 1 years (a single viral load measurement \>50 but \<500 copies/ml during this time period is allowable)
• No evidence of viral insensitivity to GS-2872 based on proviral sequencing
• No significant co-morbidities according to the investigator's opinion
• Nadir CD4 \>200 cells/µl unless treatment commenced during documented acute seroconversion
• Current CD4 count \>500 cells/µl or CD4:CD8 ratio \>1.0
• On integrase inhibitor (INSTI) or boosted protease inhibitor (bPI) based regimen at time of randomisation. If previously on non-nucleoside reverse transcriptase inhibitor (NNRTI) must have switched at least 4 weeks prior to randomisation
• Adequate haemoglobin (Hb ≥12 g/dL for males, ≥11 g/dL for females)
• Weight ≥ 50kg
• Has received at least 3 doses of vaccination against coronavirus (COVID-19), at least 4 weeks prior to randomisation
• Has received current seasonal vaccination against Influenza\*
• People of childbearing potential\*\* must agree to use hormonal contraception, intrauterine device, intrauterine hormone-releasing system, or otherwise practice complete abstinence\*\*\* from at least two weeks before the first Investigational Medicinal Product (IMP) administration, for at least 20 months after the last IMP administration, and until undetectable viral load on ART

You may not qualify if:

• Previous ischaemic heart disease (ST or non-ST myocardial infarction, Q3-risk \>20, stable angina, unstable angina, stroke)
• Any current or past history of malignancy, excluding squamous cell skin cancers
• Concurrent opportunistic infection or other co-morbidity likely to occur during the trial e.g.
• malabsorption syndromes, autoimmune disease
• Any contraindication to receipt of BHIVA recommended combination antiretrovirals
• Current treatment with injectable ART
• HTLV-1 co-infection
• Any evidence of major antiretroviral resistance mutations
• Evidence of HBV infection requiring treatment (HBsAg+, or HBcAb+ without HBsAb+)
• Evidence of HCV infection (HCVAg+ and/or HCV RNA detected)
• Individuals at high risk from severe Covid-19 disease who may be defined in accordance with NHSE guidance as vulnerable and shielded (as per the view of participant's physician)
• Current or planned systemic immunosuppressive therapy (inhaled and topical corticosteroids are allowed)
• Participation in another research study involving receipt of an investigational medicinal product (IMP) in the 3 months preceding enrolment or 5 half-lives of the investigational medicinal product, whichever is longer, or planned participation during the study period (concurrent observational studies are allowed)
• History of anaphylaxis or severe adverse reaction to antibody infusions, or hypersensitivity to GS-2872 or GS-5423 or to any constituent products or excipients thereof
• History of anaphylaxis or severe adverse reaction to any previous vaccine

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (3)

Guys and St Thomas' NHS Trust

London, SE1 7EH, United Kingdom

RECRUITING

St Mary's Clinical Trial Unit

London, W2 1NY, United Kingdom

RECRUITING

Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)

Oxford, OX3 7LJ, United Kingdom

RECRUITING

Central Study Contacts

Paola Cicconi, MD, PhD

CONTACT

00 44 1865 611425; paola.cicconi@ndm.ox.ac.uk

John Frater, MD, PhD

CONTACT

0000; john.frater@ndm.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomised to one of three arms. Participants in Arm A undergo a period of treatment interruption induced viraemia, followed by two bNAB infusions (GS-5423 and GS-2872). Participants in Arm B receive three HIV vaccines (one prime dose of two vaccines, ChAdOx1.tHIVconsv1 and ChAdOx2.HIVconsv62 and two booster doses of MVA.tHIVconsv4 after 4 and 16 weeks), followed by two bNAb infusions (GS-5423 and GS-2872). Participants in Arm C undergo a period of treatment interruption induced viraemia, followed by three HIV vaccines (one prime dose of two vaccines, ChAdOx1.tHIVconsv1 and ChAdOx2.HIVconsv62 and two booster doses of MVA.tHIVconsv4 after 4 and 16 weeks), followed by two bNAb infusions (GS-5423 and GS-2872). All participants then undergo a period of analytical treatment interruption where there responses to the interventions are measured.

Study Record Dates

• First Submitted: May 16, 2025
• First Posted: July 8, 2025
• Study Start: September 5, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: January 21, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)