RV630 - Approach to Control HIV With Immune Enhancement and Vaccination (ACHIEV
ACHIEV
1 other identifier
interventional
48
1 country
1
Brief 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 hiv-infections
Started Mar 2025
Typical duration for phase_1 hiv-infections
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 31, 2024
CompletedFirst Posted
Study publicly available on registry
July 3, 2024
CompletedStudy Start
First participant enrolled
March 27, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 1, 2027
September 16, 2025
August 1, 2025
2.3 years
May 31, 2024
September 15, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
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 Outcomes (16)
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.
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.
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.
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 the number of participants with plasma HIV-1 RNA < 1000 copies/mL at 12 and 24 weeks of
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 ART resumption for an HIV-related (virologic, immunologic, or clinical) reason d
i. Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)
- +11 more secondary outcomes
Other Outcomes (4)
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
Measure at week 0 of Step 3 in all groups, just prior to ATI.
To assess the development of anti- drug antibody toVRC07-523LS and PGDM1400LS.
Measure at week 0 of Step 3 in all groups, just prior to ATI.
To evaluate baseline ChAdOx1 and ModifiedVaccinia Ankara (MVA) serostatus and its effects onimmune response and primary outcomes.
Measure at week 0 of Step 3 in all groups, just prior to ATI.
- +1 more other outcomes
Study Arms (3)
Active Arm
ACTIVE COMPARATORActive Arm (Group 1) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Active Arm: Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20
Comparator Arm
PLACEBO COMPARATORComparator Arm (Group 2) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Comparator Arm - Group 2 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. Placebo vaccination at Step 2, Weeks 4, 12 and 20
Exploratory Arm
OTHERExploratory Arm (Group 3) will have 8 participants. This study will also enroll an Exploratory arm of newly enrolled participants of the RV 254/ WRAIR #1494 study, who are PLWH aged 18 - 60 years, diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. For the Exploratory Arm - Group 3 will receive: iv. VRC07-523LS and PGDM1400LS at Step 2, Week 0 v. ART starting at Step 2, Week 0 vi. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 vii. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28
Interventions
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 is a recombinant human IgG1 bNAb targeted against the HIV-1 V2 apex epitope region.
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 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 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, 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 (Army Liposome Formulation, ALF) is a liposomal adjuvant containing a synthetic
Normal saline (0.9% sodium chloride for injection) will be used as a placebo.
Eligibility Criteria
You may qualify if:
- Participants are eligible to be included in the protocol Step 1 only if all of the following criteria are met:
- Thai National
- Age ≥18 and ≤60 years of age
- Can read and write Thai
- Able and willing to provide written informed consent
- Confirmed HIV-1 infection (nucleic acid testing \[NAT\] and/or HIV-1 serology positive with confirmatory quantitative HIV-1 viral load) and started ART during acute infection
- Uninterrupted treatment with ART (no interruption of ART for ≥7 consecutive days or longer) since ART initiation, for ≥ 48 weeks.
- Currently on integrase inhibitor-based ART regimen (excluding long-acting injectable regimens) and no recent (≤8 weeks prior to screening) changes to ART regimen.
- a. There must be at least one documented plasma HIV-1 RNA \<50 cps/mL after the last ART change prior to screening
- Must be medically stable as confirmed by medical history, physical examination, vital signs, and clinical laboratory tests performed at screening, and as per the Investigator's discretion.
- a. If the results of the screening laboratory panel are outside the normal reference ranges, the participant may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study after discussion with the Sponsor's Representative.
- The following laboratory values at screening:
- CD4 T-cell count ≥400 cells/mm3
- Absolute neutrophil count (ANC) ˃1,000/mm3
- Hemoglobin \>11.5 g/dL
- +15 more criteria
You may not qualify if:
- Participants who meet any of the following criteria will be excluded from the study:
- 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.
- Any clinically significant acute or chronic medical condition, that in the opinion of the investigator would preclude participation including cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological disorders, that in the opinion of the investigator would preclude participation (e.g., history of seizure disorders, cardiovascular disease, bleeding/clotting disorder, autoimmune disease, malignancy, poorly controlled asthma, active tuberculosis or other systemic infections, etc.).
- Active or chronic hepatitis B virus infection (detectable HBsAg, HBV DNA, or both)
- HCV treatment or HCV RNA\>LOD within the previous 6 months
- Receipt of a licensed or Emergency Use Authorization vaccine within 4 weeks prior to study screening or plans to receive live attenuated vaccines within 4 weeks or any other licensed or Emergency Use Authorization vaccine within 2 weeks prior to or 2 weeks after any of the study investigational product administrations.
- Plans to receive an MVA-vectored licensed or Emergency Use Authorization vaccine (i.e., smallpox or Mpox vaccine) within 12 weeks prior to or 2 weeks after either of the two study MVA.tHIVconsv4 vaccine administrations.
- Previous receipt of immunoglobulin (IgG) therapy Note: Individuals who received IgGs as prophylactic therapy (e.g., for HBV or rabies exposure) \>12 months prior to screening will not be excluded.
- Previous receipt of humanized or human monoclonal antibody whether licensed or investigational Note: Individuals who received monoclonal antibody for the prevention and/or treatment of SARS-CoV-2/COVID-19 \>12 months prior to screening will not be excluded.
- Previous participation in a candidate HIV vaccine study or immune prophylaxis for HIV-1 infection with confirmed receipt of active product or with unknown receipt of active product vs placebo (i.e. remains blinded to what was actually received).
- History of use of any immunomodulatory medications within 6 months of study entry including systemic corticosteroids (\>14 days), immunosuppressants, anti-cancer drugs, interleukins, systemic interferons, systemic chemotherapy, or other medications that the site investigator feels could have an immune modulatory effect Note: Topical or inhaled corticosteroids are not prohibited.
- Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines, vaccine products, neomycin, streptomycin, gentamicin or egg products
- +71 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
The Faculty of Medicine, Chulalongkorn University/ King Chulalongkorn Memorial Hospital
Pathum Wan, Bangkok, 10330, Thailand
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Masking Details
- The participants, clinical staff, laboratory staff, Principal Investigator (PI) and the Sponsor will be blinded to vaccine/placebo allocation for Groups 1 and 2. The pharmacist with primary responsibility for vaccine dispensing will not be blinded to the treatment and maintains the randomization code and completes assignments of participants according to the randomization allocation. The contents of the syringes containing vaccine IP will be obscured and not discernable to the participant or study staff in the vaccination room. All analyses conducted prior to the completion of the study will be performed by an unblinded statistician, and results will only be presented in aggregate to protect the participant-level blind. See Section 6.4 below for unblinding procedures. Group 3 will be unblinded.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 31, 2024
First Posted
July 3, 2024
Study Start
March 27, 2025
Primary Completion (Estimated)
August 1, 2027
Study Completion (Estimated)
August 1, 2027
Last Updated
September 16, 2025
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will not share