CH505 TF chTrimer Vaccine for HIV

Recruiting at 24 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Antiretrovirals

Must not be taking: Immunomodulators, Cytotoxic chemotherapy

Disqualifiers: Opportunistic infections, Autoimmune disorders, others

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

A5422 is a phase 1, randomized, double-blind, placebo-controlled clinical trial to assess the safety, tolerability, and immunogenicity of a vaccination with stabilized CH505 TF chTrimer admixed with 3M-052-AF + Aluminum hydroxide (Alum), to assess the effect of CH505 TF chTrimer vaccine as a therapeutic vaccine in adults living with HIV-1 on suppressive antiretroviral therapy (ART) with the aim of inducing new HIV-1 Envelope (Env) B-cell neutralizing immune responses. Participants will be on study for up to 100 weeks (52 weeks on study treatment plus 48 weeks follow-up).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on a stable antiretroviral therapy (ART) regimen for at least 24 months before joining. If you are using certain medications like immunomodulators or have had recent vaccinations, you may not be eligible.

What data supports the effectiveness of the CH505 TF chTrimer Vaccine treatment for HIV?

The research on similar HIV vaccines, like the Trimer 4571, shows that they are safe and can trigger an immune response in healthy adults. Additionally, other studies on HIV vaccines have demonstrated that they can boost immune responses and maintain low levels of the virus in the body, suggesting potential benefits for the CH505 TF chTrimer Vaccine. ^{1 2 3 4 5}

How is the CH505 TF chTrimer Vaccine treatment for HIV different from other treatments?

The CH505 TF chTrimer Vaccine is unique because it uses a multivalent approach, combining different HIV-1 envelope proteins to elicit a stronger and broader neutralizing antibody response compared to single-component vaccines. This strategy aims to address the challenge of HIV's sequence diversity, potentially offering more effective protection against various strains of the virus. ^{3 4 6 7 8}

Research Team

Madhu Choudhary, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for adults with HIV-1 who are successfully managing their condition with antiretroviral therapy. They should be interested in testing a new vaccine that might improve their immune response against HIV. Specific criteria will determine eligibility.

Inclusion Criteria

CD4+ cell count greater than 200 cells/mm3 obtained within 56 days prior to study entry

HIV-1 RNA <200 copies/mL obtained within 56 days prior to study entry

White blood cell count ≥2,500 cells/mm3

Exclusion Criteria

Currently breastfeeding

I have not had any cancer in the last 5 years.

History of or active autoimmune disorders

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the CH505 TF chTrimer vaccine or placebo for 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 weeks

Treatment Details

Interventions

• CH505 TF chTrimer Vaccination

Trial Overview The study is evaluating the safety and immune response to a stabilized CH505 TF chTrimer vaccine mixed with an adjuvant (3M-052-AF) and Aluminum hydroxide in people living with HIV. It's randomized, double-blind, and placebo-controlled.

Participant Groups

Group I: Study Arm 1: CH505 TF chTrimer (300 mcg) admixed with 3M-052-AF (3 mcg) and Alum (500 mcg) Experimental Treatment 3 Interventions

Group II: Study Arm 2: Placebo (sodium chloride for injection, 0.9% USP) Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Access to Advanced Health Institute (AAHI)

Collaborator

Trials

30

Recruited

1,700+

Findings from Research

The Trimer 4571 HIV-1 vaccine was found to be safe and well-tolerated in a phase I trial involving 16 HIV-negative adults, with mild to moderate side effects and no serious adverse events reported.

The vaccine induced specific antibody responses in 44% of participants, particularly at the higher 500 mcg dose, suggesting its potential as a component in future HIV vaccine strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of an HIV-1 prefusion-stabilized envelope trimer (Trimer 4571) vaccine in healthy adults: A first-in-human open-label, randomized, dose-escalation, phase 1 clinical trial. Houser, KV., Gaudinski, MR., Happe, M., et al.[2022]

The LFn-p24C therapeutic HIV vaccine was found to be safe and well-tolerated in a Phase I trial with 30 HIV-positive volunteers, who were already on stable antiretroviral therapy.

After vaccination, participants showed significantly higher CD4 counts and 30% of those who underwent a treatment interruption did not experience viral rebound, indicating potential benefits in boosting immune response against HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic immunization in HIV infected Ugandans receiving stable antiretroviral treatment: a Phase I safety study. Kityo, C., Bousheri, S., Akao, J., et al.[2021]

The HVTN 120 trial, involving 160 healthy HIV-uninfected adults, demonstrated that the ALVAC-HIV vaccine was generally safe and well tolerated, with no significant safety concerns reported.

Among the different vaccine regimens tested, the 40 μg gp120 protein adjuvanted with AS01B produced the strongest immune responses, showing higher CD4+ T-cell responses and binding antibody levels compared to other formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein dose-sparing effect of AS01B adjuvant in a randomized preventive HIV vaccine trial of ALVAC-HIV (vCP2438) and adjuvanted bivalent subtype C gp120. Chirenje, ZM., Laher, F., Dintwe, O., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of an HIV-1 prefusion-stabilized envelope trimer (Trimer 4571) vaccine in healthy adults: A first-in-human open-label, randomized, dose-escalation, phase 1 clinical trial. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Therapeutic immunization in HIV infected Ugandans receiving stable antiretroviral treatment: a Phase I safety study. [2021]

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

HIV-1 sub-type C chimaeric VLPs boost cellular immune responses in mice. [2021]

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

Protein dose-sparing effect of AS01B adjuvant in a randomized preventive HIV vaccine trial of ALVAC-HIV (vCP2438) and adjuvanted bivalent subtype C gp120. [2023]

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

Decreased HIV-specific T-regulatory responses are associated with effective DC-vaccine induced immunity. [2019]

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

Neutralizing antibody responses to subtype B and C adjuvanted HIV envelope protein vaccination in rabbits. [2021]

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

Novel Adenovirus type 5 vaccine platform induces cellular immunity against HIV-1 Gag, Pol, Nef despite the presence of Ad5 immunity. [2021]

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

A multivalent clade C HIV-1 Env trimer cocktail elicits a higher magnitude of neutralizing antibodies than any individual component. [2018]