HIV Vaccine for HIV/AIDS

Recruiting at 6 trial locations

Overseen By Dan H Barouch, MD PHD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Boris Juelg, MD PhD

Must be taking: Suppressive ART

Must not be taking: NSAIDs, Aspirin, others

Disqualifiers: Pregnancy, Cardiovascular disease, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 24

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to be on suppressive anti-retroviral therapy (ART) for at least 48 weeks before screening and to continue it during the study. However, nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin must be stopped for 5 days before and after planned leukapheresis. Other medications are not specifically mentioned, so it's best to discuss with the study team.

What data supports the effectiveness of the HIV vaccine treatment Ad26.Mos4.HIV, MVA-BN-HIV, PGDM1400, PGT121, VRC07-523LS, VRC07-523LS?

Research on similar treatments, like the MVA-B vaccine, shows it is safe and can trigger strong immune responses, including the production of antibodies and T cells that target HIV. This suggests that the components in the new treatment might also be effective in stimulating the body's defenses against HIV. ^{1 2 3 4 5}

Is the HIV vaccine safe for humans?

The HIV vaccine candidates, including MVA-B and MVA-BN, have been tested in various trials and found to be generally safe in humans, with no serious adverse events reported. Common side effects were mild, such as injection site pain, and the vaccines were well tolerated even in people with HIV. ^{1 6 7 8 9}

What is the purpose of this trial?

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).

Research Team

Boris D Juelg, MD PHD

Principal Investigator

Beth Israel Deaconess Medical Center

Eligibility Criteria

Adults aged 18-70 with HIV, on stable ART for at least 48 weeks, and undetectable viral load. They must understand the study, consent to it, be willing to restart ART if needed, and adhere to protocol restrictions. Excluded are those with acute illness or certain medical conditions like advanced liver disease or history of significant heart issues.

Inclusion Criteria

I have been on ART for at least 48 weeks.

Each potential study participant must pass the Test of Understanding (TOU) after reading the informed consent and receiving detailed information on the study

Must be willing to undergo Analytical Treatment Interruption (ATI)

Exclusion Criteria

I have not had a severe HIV-related illness in the last 10 years.

Pregnant, breastfeeding, or planning to become pregnant while enrolled in the study

I cannot have shots, IV lines, or blood taken due to medical reasons.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

10 weeks

Vaccination and Follow-up

Participants receive Ad26.Mos4.HIV vaccine at week 0 and MVA-BN-HIV vaccine at week 12, followed by monitoring

24 weeks

Multiple visits for vaccine administration and follow-up

bNAb Administration and Washout

Administration of bNAbs PGT121, PGDM1400, and VRC07-523LS, followed by a washout period

24 weeks

bNAbs administered at weeks 24 and 28

Monitoring

Participants are monitored for safety, immunogenicity, and efficacy, including an analytical treatment interruption

24 weeks

Regular monitoring visits

Treatment Details

Interventions

• Ad26.Mos4.HIV
• MVA-BN-HIV
• PGDM1400
• PGT121
• VRC07-523LS

Trial Overview The trial is testing a vaccine regimen (Ad26.Mos4.HIV prime and MVA-BN-HIV boost) combined with antibodies (PGT121, PGDM1400, VRC07-523LS) in HIV-infected adults on ART. It's a Phase 1/2a study assessing safety, tolerability, immune response and preliminary effectiveness.

Participant Groups

Group I: Ad26.Mos4.HIV, MVA-BN-HIV Vaccine Plus PGT121, PGDM1400, and VRC07-523LS bNAbs Experimental Treatment 5 Interventions

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 II: Ad26.Mos4.HIV, MVA-BN-HIV Vaccine Plus Placebo Active Control 2 Interventions

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 III: Placebo Plus PGT121, PGDM1400, and VRC07-523LS bNAbs Active Control 3 Interventions

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.

Who Is Running the Clinical Trial?

Boris Juelg, MD PhD

Lead Sponsor

Trials

1

Recruited

40+

The University of Texas Health Science Center, Houston

Collaborator

Trials

974

Recruited

361,000+

Janssen Pharmaceuticals

Industry Sponsor

Trials

87

Recruited

208,000+

Joaquin Duato

Janssen Pharmaceuticals

Chief Executive Officer since 2022

MBA from ESADE Business School

John (Jack) Lawrence

Janssen Pharmaceuticals

Chief Medical Officer since 2023

MD from University of Virginia School of Medicine

Harvard School of Public Health (HSPH)

Collaborator

Trials

283

Recruited

17,030,000+

Orlando Immunology Center

Collaborator

Trials

6

Recruited

130+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase I safety and immunogenicity evaluation of MVA-CMDR, a multigenic, recombinant modified vaccinia Ankara-HIV-1 vaccine candidate. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Immunogenic profiling in mice of a HIV/AIDS vaccine candidate (MVA-B) expressing four HIV-1 antigens and potentiation by specific gene deletions. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a modified vaccinia Ankara-based HIV-1 vaccine (MVA-B) in HIV-1-infected patients alone or in combination with a drug to reactivate latent HIV-1. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Vector replication and expression of HIV-1 antigens by the HIV/AIDS vaccine candidate MVA-B is not affected by HIV-1 protease inhibitors. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Broad and potent cellular and humoral immune responses after a second late HIV-modified vaccinia virus ankara vaccination in HIV-DNA-primed and HIV-modified vaccinia virus Ankara-boosted Swedish vaccinees. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a modified pox vector-based HIV/AIDS vaccine candidate expressing Env, Gag, Pol and Nef proteins of HIV-1 subtype B (MVA-B) in healthy HIV-1-uninfected volunteers: A phase I clinical trial (RISVAC02). [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

A randomized phase II trial to compare safety and immunogenicity of the MVA-BN smallpox vaccine at various doses in adults with a history of AIDS. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization. [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and tolerability of recombinant modified vaccinia virus Ankara expressing an HIV-1 gag/multiepitope immunogen (MVA.HIVA) in HIV-1-infected persons receiving combination antiretroviral therapy. [2022]