Safety and Efficacy of Broadly Neutralizing Antibodies Combined With Therapeutic Vaccination for the Induction of HIV Remission
NCT Number: NCT06484335
Acronym: ACHIEV
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: HIV Infections|PLWH|ART|Acute HIV Infection
Interventions: BIOLOGICAL: VRC07-523LS|BIOLOGICAL: PGDM1400LS|BIOLOGICAL: ChAdOx1.tHIVconsv1|BIOLOGICAL: ChAdOx1.HIVconsv62|BIOLOGICAL: MVA.tHIVconsv4|BIOLOGICAL: A244d11 gp120|BIOLOGICAL: ALFQ|OTHER: Placebo
Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine
Collaborators: US Military HIV Research Program
Sex: ALL
Age: ADULT
Enrollment: 48
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2025-02-01
Completion Date: 2027-08-01
Locations: The Faculty of Medicine, Chulalongkorn University/ King Chulalongkorn Memorial Hospital, Pathum Wan, Bangkok, 10330, Thailand

Summary:
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).

Primary Outcome Measures: 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, Measured from enrollment to a minimum of 50 weeks to a maximum of 100 weeks per participant|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., Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)
Secondary Outcome Measures: 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, Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)|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, Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)|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 during ATI prior to ART resumption, Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)|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., Nadir viral load during ATI prior to ATI resumption, Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)|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., Viral load area under the curve (AUC) during the first 8 weeks after viral rebound during ATI., i. Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)|To evaluate the impact of VRC07-523LS, 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 ATI., The number of participants with plasma HIV-1 RNA \<1000 copies/mL at 12 and 24 weeks of step 3 (ATI)., Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)|To evaluate the impact of VRC07-523LS, PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on time to ART resumption for an HIV-related reason during Step 3., Time (days) from ATI to ART resumption during Step 3 (ATI), Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)|To measure the effects of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on HIV-1 RNA levels while on ART., HIV-1 RNA levels using single copy assay while on ART, Measure during step 2: from the initial administration of bNab therapy through week 22 in arms 1 and 2 and through week 30 in arm 3.|To assess the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on total HIV-1 DNA levels prior to ATI, Total HIV-1 DNA levels prior to ATI, Measure at week 0 of Step 3 in all groups, just prior to ATI.|To assess the effects of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on HIV-1 specific cellular immune responses prior to ATI, CD4 T Cell response to HIV measured by flow cytometry, Measure at week 0 of Step 3 in all groups, just prior to ATI.|To assess the effects of VRC07-523LS and PGDM1400LSin combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on HIV-1 specific humoral immune responses., Binding antibody to clade AE envelop protein measured by ELISA, Measure at week 0 of Step 3 in all groups, just prior to ATI.|To assess the effects of VRC07-523LS and PGDM1400LSin combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on HIV-1 specific humoral immune responses., Measure Antibody Dependent Cytotoxicity using clade AE protein coated target cells, Measure at week 0 of Step 3 in all groups, just prior to ATI.|To assess the effects of VRC07-523LS and PGDM1400LSin combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on HIV-1 specific humoral immune responses., Measure Antibody Dependent Cellular Phagocytosis using clade AE protein coated target cells, Measure at week 0 of Step 3 in all groups, just prior to ATI.|To assess the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on the HIV-1 reservoir prior to ATI, Total HIV DNA measured by quantitative PCR, Measure at week 0 of Step 3 in all groups, just prior to ATI.|To assess the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on the HIV-1 reservoir prior to ATI, Total HIV intact DNA measured by the Intact Proviral DNA Assay, Measure at week 0 of Step 3 in all groups, just prior to ATI.|To assess the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on the HIV-1 reservoir prior to ATI, Total Quantitative Infectious HIV measured by the QVOA assay, Measure at week 0 of Step 3 in all groups, just prior to ATI.|To assess the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on the HIV-1 reservoir prior to ATI, Total HIV cell associate RNA measured by the quantitative RNA PCR, Measure at week 0 of Step 3 in all groups, just prior to ATI.|To characterize the pharmacokinetics of VRC07-523LS and PGDM1400LS., Concentration of VRC07-523LS during ATI by Meso Scale Discovery (MSD), Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)|To characterize the pharmacokinetics of VRC07-523LS and PGDM1400LS., Concentration of PGDM1400LS during ATI by MSD, Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)