Safety, Immunogenicity, Efficacy of Ad26.Mos4.HIV, MVA-BN-HIV and PGT121, PGDM1400, and VRC07-523LS in HIV-1-Infected Adults
A Safety, Immunogenicity and Efficacy Phase 1/2a Study of a Heterologous Ad26.Mos4.HIV, MVA-BN-HIV Vaccine Regimen Plus Broadly Neutralizing Antibodies PGT121, PGDM1400, and VRC07-523LS in HIV-1-Infected Adults on Suppressive ART
3 other identifiers
interventional
36
1 country
6
Brief Summary
A multicenter, randomized, parallel-group, placebo-controlled, double-blind, Phase 1/2a clinical study to investigate the safety, tolerability, immunogenicity and exploratory efficacy of a vaccine regimen consisting of an Ad26.Mos4.HIV prime and a boost with Modified Vaccinia Ankara (MVA)-BN-HIV in combination with broadly neutralizing antibodies (bNAb) PGT121, PGDM1400, and VRC07-523LS in human immunodeficiency virus type 1 (HIV-1)-infected study participants on suppressive anti-retroviral therapy (ART).
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
Started Apr 2022
Longer than P75 for phase_1 hiv
6 active sites
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
July 5, 2021
CompletedFirst Posted
Study publicly available on registry
July 30, 2021
CompletedStudy Start
First participant enrolled
April 1, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 28, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2026
CompletedJanuary 12, 2026
January 1, 2026
3.9 years
July 5, 2021
January 8, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (7)
Percentage of Participants With Solicited Local Adverse Events (AEs) as a Measure of Safety and Tolerability
Solicited local AEs: erythema, swelling/induration, and pain/tenderness will be assessed.
7 days post-investigational product administration
Percentage of Participants With Solicited Systemic AEs as a Measure of Safety and Tolerability
Solicited systemic AEs: fever (temperature measurement), fatigue, headache, nausea, myalgia, and chills will be assessed.
7 days post-investigational product administration
Percentage of Participants With Unsolicited AEs as a Measure of Safety and Tolerability
An Unsolicited AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Approximately up to 72 weeks
Percentage of Participants With Adverse Events of Special Interest (AESIs)
AESIs and potential AESIs are judged to be of special interest because of clinical importance, known or suspected class effects and include thrombotic events and symptomatic thrombocytopenia.
From first vaccination until 6 months after last vaccination.
Frequency of Epitope Recognition by Enzyme-Linked Immunospot (ELISPOT)
Assays of peptide pool sets covering the Gag, Env or Pol will be evaluated by standard enzyme linked immunospot assay (ELISPOT).
Up to post-vaccination follow-up period until Week 72
Total IgG and Subclass Specific Antibody Titer
Total immunoglobulin G (IgG) and subclass (IgG1-4) specific antibody titers (binding antibody) to envelope (Env) proteins representing Clades A, B, and C, as well as Mosaic antigens.
Up to post-vaccination follow-up period until Week 72 ]
Antiviral activity - Percentage of participants who maintain plasma HIV RNA <1000 copies/mL
Proportion of participants who remain off ART and maintaining plasma HIV RNA \<1000 copies/mL for at least two thirds of the time between 24 and 72 weeks of analytical treatment interruption (ATI).
Time between week 24 and week 72 week
Secondary Outcomes (6)
Measurement of the HIV-1 reservoir (dQVOA)
At baseline, Week 24 and Week 32
Measurement of intact proviral DNA
At baseline, Week 24 and Week 32
Compare the time to viral rebound (defined as confirmed plasma HIV RNA levels ≥1,000 copies/mL) following Ad26.Mos4.HIV, MVA-BN-HIV and placebo with the results of the rates of viral rebound as observed in historical controls.
Week 48
To evaluate PGT121, VRC07-523LS and PGDM1400 serum levels at which viral rebound is detected during the analytical treatment interruption.
From start of ATI until the date of HIV RNA >1000 copies/ml assessed up to week 72
HIV genotyping of circulating virus
From start of ATI until the date of HIV RNA >1000 copies/ml assessed up to week 72
- +1 more secondary outcomes
Study Arms (3)
Ad26.Mos4.HIV, MVA-BN-HIV Vaccine Plus PGT121, PGDM1400, and VRC07-523LS bNAbs
EXPERIMENTALParticipants will receive Ad26.Mos4.HIV vaccine at week 0 and MVA-BN-HIV vaccine at week 12. The bNAbs PGT121, PGDM1400, and VRC07-523LS will be administered at week 24, and the bNAbs PGT121 and PGDM1400 will be administered at week 28.
Ad26.Mos4.HIV, MVA-BN-HIV Vaccine Plus Placebo
ACTIVE COMPARATORParticipants will receive Ad26.Mos4.HIV vaccine at week 0 and MVA-BN-HIV vaccine at week 12. Placebo will be administered at week 24, and at week 28.
Placebo Plus PGT121, PGDM1400, and VRC07-523LS bNAbs
ACTIVE COMPARATORParticipants will receive Placebo at week 0 and 12. The bNAbs PGT121, PGDM1400, and VRC07-523LS will be administered at week 24, and the bNAbs PGT121 and PGDM1400 will be administered at week 28.
Interventions
Ad26.Mos4.HIV is a tetravalent vaccine containing Mos1.Env, Mos2S.Env, Mos1.Gag-Pol, and Mos2.Gag-Pol HIV-1 proteins.
MVA-BN-HIV is a monovalent vaccine comprising a single Modified Vaccinia Ankara - Bavarian Nordic (MVA-BN®) vector encoding Mos1.Env, Mos2S.Env, Mos1.Gag-Pol, and Mos2.Gag-Pol HIV-1 proteins.
PGT121 is a human mAb that targets the HIV-1 V3 glycan, centered on N332.
PGDM1400 is a human mAb that targets the HIV-1 V2 glycan, centered on N160.
VRC-HIVMAB075-00-AB (VRC07-523LS) is a human monoclonal antibody (mAb) that targets the HIV-1 CD4 binding site.
Eligibility Criteria
You may qualify if:
- Each potential study participant must pass the Test of Understanding (TOU), indicating that he or she understands the purpose of, and procedures required for the study, after reading the informed consent and after the investigator or designee has provided detailed information on the study and has answered the potential study participant's questions. Each study participant must subsequently sign the ICF, indicating that he or she is willing to participate in the study.
- Each study participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
- Study participants are ≥18 to ≤70 years old on the day of signing the ICF.
- Each study participant must have documented HIV-1 infection.
- Must be on suppressive ART for at least 48 weeks prior to screening. ART is defined as a combination therapy regimen including at least 2 compounds, e.g., integrase inhibitor and nucleoside reverse transcriptase inhibitors (such as DovatoTM) or more than 2 compounds, e.g., 2x nucleoside reverse transcriptase inhibitors plus integrase inhibitor.
- Must have a plasma HIV RNA \<50 cps/mL at screening and at least 1 documented evidence of plasma HIV RNA \<50 cps/mL after the last ART change.
- Must be willing to undergo ATI.
- 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.
- Ability and willingness to restart ART according to study guidelines.
- Each study participant must meet the following laboratory criteria prior to randomization:
- Hemoglobin: Women ≥10.5 g/dL; Men ≥11.0 g/dL
- White cell count: 2,500 to 11,000 cells/mm3, inclusive
- Absolute neutrophil count: \>1,000 cells/mm3
- Platelets: 125,000 to 450,000 per mm3, inclusive
- Screening serum liver enzymes (e.g., alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], total bilirubin): within the normal reference ranges at baseline
- +5 more criteria
You may not qualify if:
- Anyone who is pregnant, breastfeeding, or planning to become pregnant while enrolled in this study.
- Anyone with contraindication to intramuscular injections, placement of intravenous lines, and blood draws eg, bleeding disorders. NOTE: nonsteroidal anti- inflammatory drugs (NSAIDS) and acetylsalicylic acid containing preparations have to be stopped for 5 days before and after planned leukapheresis.
- Anyone with acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature ≥38.0oC within 24 hours prior to the first dose of study vaccine; enrollment at a later date is permitted.
- Any history of an HIV-associated malignancy (including Kaposi's sarcoma), and any type of lymphoma, or virus-associated cancers.
- Active or recent non-HIV-associated malignancy requiring systemic chemotherapy or surgery in the 36 months prior to Stage 1 randomization or for whom such therapies are expected in the next 12 months (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence).
- Anyone with a history of an underlying clinically significant acute or uncontrolled chronic medical condition or physical examination findings for which, in the opinion of the investigator, participation would not be in the best interest of the study participant.
- History or current clinical atherosclerotic cardiovascular disease, as defined by 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, including a previous diagnosis of any of the following:
- Acute myocardial infarction
- Acute coronary syndromes
- Stable or unstable angina
- Coronary or other arterial revascularization
- Stroke
- TIA
- Peripheral arterial disease presumed to be of atherosclerotic origin
- Anyone with a history of HIV-related illness under CDC Category C (except for recurrent pneumonia) within 10 years prior to screening, based on available medical history and assessed by the investigator for clinical relevance.
- +29 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Boris Juelg, MD PhDlead
- Janssen Pharmaceuticalscollaborator
- Harvard School of Public Health (HSPH)collaborator
- National Institute of Allergy and Infectious Diseases (NIAID)collaborator
Study Sites (6)
UCLA CARE (Center for AIDs Research and Education)
Los Angeles, California, 90035, United States
Orlando Immunology Center
Orlando, Florida, 32803, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115, United States
Washington University Clinical Trials Unit
St Louis, Missouri, 63110, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
University of Washington Positive Research
Seattle, Washington, 98104, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Boris D Juelg, MD PHD
Beth Israel Deaconess Medical Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Physician
Study Record Dates
First Submitted
July 5, 2021
First Posted
July 30, 2021
Study Start
April 1, 2022
Primary Completion
February 28, 2026
Study Completion
April 30, 2026
Last Updated
January 12, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- Immediately following publication. No end date.
- Access Criteria
- Anyone who wishes to access the data.
We plan to share all IPD that underlie the results reported in a respective publication, after deidentification (text, tables, figures, and appendices).