Safety, Immunogenicity, Efficacy of Ad26.Mos4.HIV, MVA-BN-HIV and PGT121, PGDM1400, and VRC07-523LS in HIV-1-Infected Adults

NCT ID: NCT04983030

Last Updated: 2026-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-01

Study Completion Date

2026-04-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The study will enroll 36 adults randomized in a 1:1:1 ratio to 3 groups (vaccines+ bNAbs, vaccine+placebo, placebo+bNAbs), respectively. The study population will include HIV-infected adults who are on suppressive ART for at least 48 weeks prior to screening. The study comprises of a screening period of 10 weeks (Stage 0), a 24-week vaccination and follow-up period (Stage 1), a 4-week bNAb administration period and a 20-week bNAb washout period (Stage 2), and a 24-week monitoring period (Stage 3). An analytical antiretroviral treatment interruption (ATI) to assess rates of sustained virologic suppression will be conducted during Stages 2-3. Participants will record solicited signs and symptoms in a diary on the evening after each study drug administration and then daily for the next 7 days. Further safety evaluations will include monitoring of AEs, physical examinations, vital sign measurements, clinical laboratory tests (including urinalysis, CD4 count and HIV RNA), and for women, also pregnancy testing. Blood samples will be taken at specific clinic visits to assess immune and virologic responses as well as the pharmacokinetics and pharmacodynamics of bNAbs.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

HIV Acquired Immunodeficiency Syndrome Immunologic Deficiency Syndrome, Acquired Sexually Transmitted Diseases, Viral Retroviridae Infections

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Ad26.Mos4.HIV, MVA-BN-HIV Vaccine Plus PGT121, PGDM1400, and VRC07-523LS bNAbs

Participants 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.

Group Type EXPERIMENTAL

Ad26.Mos4.HIV

Intervention Type BIOLOGICAL

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

Intervention Type BIOLOGICAL

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

Intervention Type BIOLOGICAL

PGT121 is a human mAb that targets the HIV-1 V3 glycan, centered on N332.

PGDM1400

Intervention Type BIOLOGICAL

PGDM1400 is a human mAb that targets the HIV-1 V2 glycan, centered on N160.

VRC07-523LS

Intervention Type BIOLOGICAL

VRC-HIVMAB075-00-AB (VRC07-523LS) is a human monoclonal antibody (mAb) that targets the HIV-1 CD4 binding site.

Ad26.Mos4.HIV, MVA-BN-HIV Vaccine Plus Placebo

Participants 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.

Group Type ACTIVE_COMPARATOR

Ad26.Mos4.HIV

Intervention Type BIOLOGICAL

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

Intervention Type BIOLOGICAL

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.

Placebo Plus PGT121, PGDM1400, and VRC07-523LS bNAbs

Participants 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.

Group Type ACTIVE_COMPARATOR

PGT121

Intervention Type BIOLOGICAL

PGT121 is a human mAb that targets the HIV-1 V3 glycan, centered on N332.

PGDM1400

Intervention Type BIOLOGICAL

PGDM1400 is a human mAb that targets the HIV-1 V2 glycan, centered on N160.

VRC07-523LS

Intervention Type BIOLOGICAL

VRC-HIVMAB075-00-AB (VRC07-523LS) is a human monoclonal antibody (mAb) that targets the HIV-1 CD4 binding site.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Ad26.Mos4.HIV

Ad26.Mos4.HIV is a tetravalent vaccine containing Mos1.Env, Mos2S.Env, Mos1.Gag-Pol, and Mos2.Gag-Pol HIV-1 proteins.

Intervention Type BIOLOGICAL

MVA-BN-HIV

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.

Intervention Type BIOLOGICAL

PGT121

PGT121 is a human mAb that targets the HIV-1 V3 glycan, centered on N332.

Intervention Type BIOLOGICAL

PGDM1400

PGDM1400 is a human mAb that targets the HIV-1 V2 glycan, centered on N160.

Intervention Type BIOLOGICAL

VRC07-523LS

VRC-HIVMAB075-00-AB (VRC07-523LS) is a human monoclonal antibody (mAb) that targets the HIV-1 CD4 binding site.

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. 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.
2. Each study participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
3. Study participants are ≥18 to ≤70 years old on the day of signing the ICF.
4. Each study participant must have documented HIV-1 infection.
5. 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.
6. 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.
7. Must be willing to undergo ATI.
8. 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.
9. Ability and willingness to restart ART according to study guidelines.
10. 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
* Creatinine: \<1.2 x ULN
* Estimated glomerular filtration rate ≥ 60 mL/min
* CD4+: \>450 cells/mm3 at screening and at least 1 documented result \>300 cells/mm3 during 48 weeks before randomization (for nadir, see exclusion criterion 9)
* Troponin: \<1 x ULN
11. For participants who are able to become pregnant, negative serum or urine pregnancy test (with a sensitivity of 15-25 mIU/mL) within 24 hours prior to Stage 1 randomization
12. A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction starting from the first vaccination at Week 0 visit and for a period of 24 weeks after last dose of bNAb.

Exclusion Criteria

1. Anyone who is pregnant, breastfeeding, or planning to become pregnant while enrolled in this study.
2. 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.
3. 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.
4. Any history of an HIV-associated malignancy (including Kaposi's sarcoma), and any type of lymphoma, or virus-associated cancers.
5. 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).
6. 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.
7. 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
8. 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.
9. Anyone with a history of repeated CD4+ \<200 cells/mm3, based on available medical history and assessed by the investigator for clinical relevance. .
10. Current receipt of ART other than nucleoside reverse transcriptase inhibitor and integrase inhibitor.
11. Anyone who had major surgery (per the investigator's judgment), within 12 weeks before dosing, or has not have fully recovered from surgery, or has surgery planned during the time the study participant is expected to participate in the study or within 6 months after the last dose of study vaccine administration.
12. Anyone with a history of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with permanent sequelae, clinically significant arrhythmia (including any arrhythmia requiring medication, treatment, or clinical follow-up).
13. Anyone with an ECG with reading and showing clinically significant findings, or features that would interfere with the assessment of myocarditis/pericarditis.
14. Current advanced liver disease (non-alcoholic fatty liver disease, steatohepatitis, or alcoholic liver disease) with known or suspected cirrhosis or fibrosis score ≥F2.
15. Anyone with chronic active hepatitis B (measured by hepatitis B surface antigen test) or active hepatitis C (measured by hepatitis C virus \[HCV\] antibody test; if positive, HCV RNA polymerase chain reaction test will be used to confirm active versus past HCV infection) or syphilis infection that has not been effectively treated. Positive syphilis serology due to past effectively treated infection is not exclusionary.
16. Anyone with active, untreated gonorrhea or chlamydia infection will be referred to a clinician for appropriate treatment. If chlamydia and/or gonorrhea treatment is successfully completed, the participant is eligible for a repeat gonorrhea or chlamydia screening test and potential study entry.
17. Anyone with thyroidectomy or active thyroid disease requiring medication during the last 12 months (Not excluded: a stable thyroid supplementation).
18. Anyone with history of HIV-associated neurocognitive disease or progressive multifocal leukoencephalopathy.
19. Anyone who has had major psychiatric illness and/or drug or alcohol abuse which in the investigator's opinion would compromise the study participant's safety and/or compliance with the study procedures.
20. Anyone with a history of thrombosis with thrombocytopenia syndrome (TTS), or Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS)
21. Anyone who received treatment with immunoglobulins in the 2 months or blood products in the 4 months before the planned administration of the first dose of study vaccine or has any plans to receive such treatment during the study. Prior recipients of anti-HIV bNAbs, independently of the timing, are excluded.
22. Anyone who received or plans to receive:

1. licensed live attenuated vaccines - within 28 days before or after planned administration of any of the study products.
2. other licensed (not live) vaccines - within 14 days before or after planned administration of any of the study products.
3. SARS-CoV-2 vaccines under Emergency Use Authorization (EUA) by the FDA - within 28 days before or after planned administration of any of the study products.
23. Anyone who received an investigational drug (not under EUA by the FDA) or used an invasive investigational medical device within 30 days or received an investigational vaccine within 6 months before the planned administration of the first dose of study vaccine. Receipt of prophylactic or therapeutic HIV vaccine candidate at any time is always exclusionary.
24. Anyone who is currently enrolled or plans to participate in another investigational study during the course of this study.
25. Anyone who has known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products (including any of the constituents of the study vaccines) and specifically to neomycin or streptomycin or egg products.
26. Anyone with a history of chronic urticaria (recurrent hives) or a history of chronic or recurrent eczema and/or atopic dermatitis.
27. Anyone with abnormal function of the immune system resulting from:

1. Clinical conditions (e.g., autoimmune disease or immunodeficiency that are not HIV related).
2. Chronic or recurrent use of systemic corticosteroids.
3. Administration of antineoplastic and immunomodulating agents or radiotherapy.
28. Anyone with history of acute polyneuropathy(e.g.,Guillain-Barré syndrome).
29. Anyone who cannot communicate reliably with the investigator.
30. Known resistance to 1 or more drugs in 2 or more ARV drug classes.
31. Weight \>115kg.
32. Anyone who, in the opinion of the investigator, is unlikely to adhere to the requirements of the study, or is unlikely to complete the full course of vaccination and observation.
33. Any employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator, or an employee of the sponsor (or its partners).
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Janssen Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Harvard School of Public Health (HSPH)

OTHER

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Boris Juelg, MD PhD

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Boris Juelg, MD PhD

Physician

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Boris D Juelg, MD PHD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

UCLA CARE (Center for AIDs Research and Education)

Los Angeles, California, United States

Site Status

Orlando Immunology Center

Orlando, Florida, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Washington University Clinical Trials Unit

St Louis, Missouri, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

University of Washington Positive Research

Seattle, Washington, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

5U01AI145801

Identifier Type: NIH

Identifier Source: secondary_id

View Link

38743

Identifier Type: REGISTRY

Identifier Source: secondary_id

IPCAVD014/HTX1004

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.