CH505 TF chTrimer Vaccine for HIV Prevention

Recruiting at 2 trial locations

Overseen By Lindsey Baden, M.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

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

Must be taking: PrEP

Must not be taking: Glucocorticoids, Blood products

Disqualifiers: Pregnancy, Breast-feeding, Seizure disorder, Asthma, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 23

Duration: 12 months

52 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new vaccine called CH505 TF chTrimer in healthy adults. The vaccine is combined with substances to see if it helps the immune system produce strong antibodies. The goal is to ensure the vaccine is safe and effective.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain medications like systemic glucocorticoids, recent vaccines, and investigational agents may affect eligibility. It's best to discuss your specific medications with the trial team.

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

The research shows that a similar HIV vaccine containing gp120 antigens induced strong immune responses in healthy adults, which lasted for 18 months. This suggests that vaccines targeting similar components may be effective in stimulating the immune system against HIV. ^{1 2 3 4 5}

Is the CH505 TF chTrimer Vaccine for HIV Prevention safe for humans?

The CH505 TF chTrimer Vaccine for HIV Prevention has not been specifically mentioned in the provided research articles, but similar HIV vaccines have been tested and found to be generally safe in humans, with minimal adverse events reported. ^{1 6 7 8 9}

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

The CH505 TF chTrimer treatment is unique because it uses a highly diverse set of HIV envelope proteins to stimulate a broad neutralizing antibody response, potentially offering better protection against various HIV strains compared to traditional vaccines that use a single type of envelope protein. ^{10 11 12 13 14}

Research Team

Kenneth H Mayer, M.D.

Principal Investigator

Beth Israel Deaconess Medical Center

Lindsey R Baden, M.D.

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

Healthy adults aged 18-55 who are not pregnant, breastfeeding, or at high risk for HIV. Participants must be in good health, available for follow-up visits, willing to undergo certain medical procedures like lymph node aspiration and leukapheresis, and agree to use effective birth control. Exclusions include recent receipt of blood products or certain vaccines, serious vaccine reactions, asthma requiring frequent steroid use or emergency care, immune-mediated diseases, drug abuse history.

Inclusion Criteria

Negative for Hepatitis B surface antigen

Negative results for HIV infection by an FDA-approved enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA)

I do not have hepatitis C.

Exclusion Criteria

History of allergy to local anesthetic

I haven't taken any experimental drugs with a short half-life in the last 4 weeks.

I received the Monkeypox vaccine within the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CH505 TF chTrimer vaccine with 3M-052-AF +/- Alum adjuvant via two intramuscular injections administered five times throughout the study

12 months

5 visits (in-person) at months 0, 2, 4, 8, and 12

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Scheduled clinic visits up to 18 months

Long-term follow-up

Participants have a follow-up safety assessment 12 months after their final vaccination

12 months

Treatment Details

Interventions

• CH505 TF chTrimer

Trial Overview The trial is testing the CH505 TF chTrimer vaccine with different doses of the adjuvants 3M-052-AF and Alum to evaluate safety and how well it generates an immune response (immunogenicity). Part A uses a specific dose combination while Part B tests varying doses/combinations to find the best balance between effectiveness and side effects.

Participant Groups

Group I: Group 4: Treatment Experimental Treatment 2 Interventions

CH505 chTrimer 300 mcg admixed with (5 mcg) 3M-052-AF administered at months 0, 2, 4, 8 and 12.

Group II: Group 3: Treatment Experimental Treatment 3 Interventions

CH505 cTrimer, 300 mcg admixed with (3 mcg) 3M-052-AF + (500 mcg) Aluminum Hydroxide Ssuspension (Alum) administered at months 0, 2, 4, 8 and 12.

Group III: Group 2: Treatment Experimental Treatment 2 Interventions

CH505 TF chTrimer 300 mcg admixed with (3 mcg) 3M-052-AF administered at months 0, 2, 4, 8 and 12.

Group IV: Group 1:Treatment Experimental Treatment 3 Interventions

CH505 TF chTrimer 300 mcg admixed with (5 mcg) 3M-052-AF + (500 mcg) Aluminum Hydroxide suspension, administered at months 0, 2, 4, 8 and 12.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Findings from Research

Daily oral PrEP with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is effective for men who have sex with men, but its effectiveness in cisgender women has been inconsistent, highlighting the need for diverse HIV prevention options.

Newer strategies like injectable long-acting cabotegravir have shown superior effectiveness compared to daily oral TDF/FTC, and ongoing studies are exploring other formulations like islatravir and lenacapavir, which may offer more flexible and effective prevention methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges and Opportunities for Preexposure Prophylaxis. Cambou, MC., Landovitz, RJ.[2021]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Strong and persistent CD4+ T-cell response in healthy adults immunized with a candidate HIV-1 vaccine containing gp120, Nef and Tat antigens formulated in three Adjuvant Systems. [2010]

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

Challenges and Opportunities for Preexposure Prophylaxis. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

It's Time: The Case for PrEP as an Active Comparator in HIV Biomedical Prevention Trials. [2021]

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

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

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

Safety and immune responses after a 12-month booster in healthy HIV-uninfected adults in HVTN 100 in South Africa: A randomized double-blind placebo-controlled trial of ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59 vaccines. [2021]

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

Safety and immunogenicity of a high-titered canarypox vaccine in combination with rgp120 in a diverse population of HIV-1-uninfected adults: AIDS Vaccine Evaluation Group Protocol 022A. [2020]

7. 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]

8. 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]

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

Safety and immunogenicity of combinations of recombinant subtype E and B human immunodeficiency virus type 1 envelope glycoprotein 120 vaccines in healthy Thai adults. [2022]

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

Comparison of neutralizing antibody responses elicited from highly diverse polyvalent heterotrimeric HIV-1 gp140 cocktail immunogens versus a monovalent counterpart in rhesus macaques. [2022]

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

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

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

Antigenicity and immunogenicity of a trimeric envelope protein from an Indian clade C HIV-1 isolate. [2021]

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

Comparison of immunity generated by nucleic acid-, MF59-, and ISCOM-formulated human immunodeficiency virus type 1 vaccines in Rhesus macaques: evidence for viral clearance. [2020]

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

Immunogenicity of a novel Clade B HIV-1 vaccine combination: Results of phase 1 randomized placebo controlled trial of an HIV-1 GM-CSF-expressing DNA prime with a modified vaccinia Ankara vaccine boost in healthy HIV-1 uninfected adults. [2020]