Health Trials

RV630 - Approach to Control HIV With Immune Enhancement and Vaccination (ACHIEV

ConditionsHIV InfectionsPLWHARTAcute HIV Infection
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-60
SponsorHenry M. Jackson Foundation for the Advancement of Military Medicine

About this trial

This is a phase I, randomized, double-blind, placebo-controlled clinical trial to investigate the safety of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62 prime, MVA.tHIVconsv4 and A244d11gp120/ALFQ vaccination, and the impact on viral load setpoint during analytic treatment interruption (ATI) in people living with human immunodeficiency virus-1 (HIV-1, PLWH) who have initiated or will initiate antiretroviral therapy (ART) during acute HIV-1 infection (AHI).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Thai National

Age ≥18 and ≤60 years of age

Can read and write Thai

Able and willing to provide written informed consent

Disqualifiers

Weight <50 kg or > 115 kg

Presence of HLA B*57:01 allele associated with viral control.

Anyone with contraindication to intramuscular injections, placement of intravenous lines, and blood draws

Acute or serious illness requiring systemic treatment and/or hospitalization within 90 days prior to entry.

Trial design

Design model

Parallel

Treatments tested in this trial

  • VRC07-523LS

    Biological/Vaccine

    VRC07-523LS (VRC-HIVMAB075-00-AB) is a recombinant human immunoglobulin G1 (IgG1) broadly neutralizing monoclonal antibody (bNAb) directed against the HIV-1 CD4 binding site

  • PGDM1400LS

    Biological/Vaccine

    PGDM1400LS is a recombinant human IgG1 bNAb targeted against the HIV-1 V2 apex epitope region.

  • ChAdOx1.tHIVconsv1

    Biological/Vaccine

    ChAdOx1.tHIVconsv1 is a replication-deficient virus expressing six conserved sub-protein regions of Gag and Pol (regions 1-6) of HIV-1 as one chimeric protein designated HIVconsv1.

  • ChAdOx1.HIVconsv62

    Biological/Vaccine

    ChAdOx1.HIVconsv62 is a replication-deficient virus expressing six conserved sub-protein regions of Gag and Pol (regions 1-6) of HIV-1 as one chimeric protein designated HIVconsv62.

  • MVA.tHIVconsv4

    Biological/Vaccine

    MVA.tHIVconsv4 is a recombinant, non-replicating Modified Vaccinia Ankara (MVA) virus expressing six conserved sub-protein regions of Gag and Pol (regions 1-6) of HIV-1 as one chimeric protein designated tHIVconsv4.

  • A244d11 gp120

    Biological/Vaccine

    A244d11 gp120, consists of the gp120 envelope glycoprotein HIV-1 subtype CRF\_01AE A244 derived from the CM244 CRF\_01AE strain, with an 11 amino N-terminal deletion. It is a modification of the A244 rgp120 immunogen from the AIDSVAX®B/E vaccine.

  • ALFQ

    Biological/Vaccine

    ALFQ (Army Liposome Formulation, ALF) is a liposomal adjuvant containing a synthetic

  • Placebo

    Other intervention

    Normal saline (0.9% sodium chloride for injection) will be used as a placebo.

Treatment groups

48 Participants
are divided into 3 treatment groups
Group A: Active ArmActive comparator 7 interventions
Group B: Comparator ArmPlacebo comparator 3 interventions
Group C: Exploratory ArmOther 7 interventions

Trial outcomes

Primary outcomes

1

To evaluate the safety of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination in PLWH who initiated ART during AHI.

Occurrence of ≥ grade 3 AE or SAE that are possibly, probably, or definitely related to the IPs during the study

Time frame
Measured from enrollment to a minimum of 50 weeks to a maximum of 100 weeks per participant
2

To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on viral load setpoint after viral rebound during ATI.

Viral Load setpoint after 2 weeks post viral rebound during ATI.

Time frame
Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)

Secondary outcomes

1

To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on time to first documented HIV-1 RNA viral rebound of ≥50 copies/mL following ATI.

Time (days) from ATI to first documented HIV-1 RNA viral rebound of ≥50 copies/mL

Time frame
Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)
2

To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on time to first documented HIV-1 RNA viral rebound of ≥1000 copies/mL following ATI.

Time (days) from ATI to first documented HIV-1 RNA viral rebound of ≥1000 copies/mL

Time frame
Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)
3

To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on viral rebound dynamics during ATI.

Peak viral load, nadir viral load, and viral load area under the curve (AUC) during the first 8 weeks after viral rebound.

Time frame
Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)
4

To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on the number of participants with plasma HIV-1 RNA < 1000 copies/mL at 12 and 24 weeks of

The number of participants with plasma HIV-1 RNA \< 1000 copies/mL at 12 and 24 weeks of ATI.

Time frame
Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)

Other outcomes

1

To assess the impact of VRC07-523LS andPGDM1400LS in combination withChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62,MVA.tHIVconsv4 and A244d11 gp120/ALFQvaccination on the HIV reservoir when started at thetime of AHI and ART initiation

Measurements of HIV-1 reservoir using assaysbased on contemporary literature that may includebut are not limited to total and/or intact HIV-1DNA, quantitative infectious virus outgrowth(qVOA), cell- associated HIV-1 RNA, and relatedassays prior to and following ATI

Time frame
Measure at week 0 of Step 3 in all groups, just prior to ATI.
2

To assess the development of anti- drug antibody toVRC07-523LS and PGDM1400LS.

Levels of ADA to VRC07-523LS andPGDM1400LS.

Time frame
Measure at week 0 of Step 3 in all groups, just prior to ATI.
3

To evaluate baseline ChAdOx1 and ModifiedVaccinia Ankara (MVA) serostatus and its effects onimmune response and primary outcomes.

ChAdOx1 nAbs titer at baseline and Vaccinia-virus-specific nAbs titer at baseline.

Time frame
Measure at week 0 of Step 3 in all groups, just prior to ATI.
4

To characterize participant experiences in the trialand preferences about participation in HIV remissiontrials with treatment interruptions

Responses to study participation questionnaires and pilot discrete choice experiment survey

Time frame
Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Henry M. Jackson Foundation for the Advancement of Military Medicine

Lead sponsor

US Military HIV Research Program

Collaborator

Source ClinicalTrials.gov
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