CH505 TF chTrimer Vaccine for HIV Prevention

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new HIV prevention vaccine, CH505 TF chTrimer, assessing its safety and its ability to trigger an immune response. Researchers are experimenting with different combinations of vaccine ingredients to identify the most effective mix for combating HIV. The study seeks healthy adults at low risk for HIV who have not previously received an investigational HIV vaccine. Participants should be willing to attend follow-ups and adhere to safety guidelines. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the CH505 TF chTrimer vaccine, currently under testing to prevent HIV, has been studied for safety in people. In earlier studies, researchers administered this vaccine to both healthy adults and people with HIV. The results indicated that the vaccine was generally well-tolerated. Most side effects were mild or moderate, such as soreness at the injection site or temporary tiredness, with no serious side effects linked to the vaccine itself.

This current trial is in the early stages, focusing primarily on safety and the body's reaction to the vaccine. Researchers are closely monitoring the treatment to ensure participant safety. The vaccine is also being tested with varying amounts of an adjuvant, a substance that can enhance the body's response to the vaccine. This helps researchers determine the best combination for safety and effectiveness.

Overall, while more information is needed, early studies suggest the vaccine is generally safe with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the CH505 TF chTrimer vaccine for HIV prevention because it presents a novel approach compared to existing options. While most HIV prevention strategies involve antiretroviral drugs like PrEP, which require daily intake, this vaccine aims to stimulate the immune system to provide long-term protection with fewer doses. The vaccine utilizes a unique mechanism by combining a trimeric protein structure with an adjuvant, 3M-052-AF, and sometimes aluminum hydroxide, to enhance the body's immune response against HIV. This could potentially offer a more sustainable and convenient prevention method with fewer side effects, making it a promising alternative for individuals at risk of HIV.

What evidence suggests that this trial's treatments could be effective for HIV prevention?

Research has shown that the CH505 TF chTrimer vaccine is promising in creating strong immune responses. In an earlier study, a similar vaccine with gp120 antigens provided lasting immunity in healthy adults for up to 18 months. Another study found that the CH505 TF chTrimer protected 90% of monkeys from a virus similar to HIV. These results suggest that the vaccine might help prevent HIV in humans. In this trial, participants will receive different formulations of the CH505 TF chTrimer vaccine to assess its ability to increase specific B cells, which help fight infections as part of the immune system. ^{1 3 4 5 6}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04915768

Study Details | NCT04915768 | Evaluating the Safety and ... A First-in-human Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Stabilized CH505 TF chTrimer in Healthy, HIV-uninfected Adult Participants.

2. withpower.com withpower.com/trial/phase-1-hiv-infections-4-2021-1557c

CH505 TF chTrimer Vaccine 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10034035/

Stabilized HIV-1 envelope immunization induces neutralizing ... Thus, immunization with stabilized CH505 TF chTrimer elicited protected from intrarectal low-dose SHIV CH505 challenge, with protection of 90% of macaques ...

4. actgnetwork.org actgnetwork.org/clinical-trial/a5422-ch505-tf-chtrimer-vaccination-in-adults-living-with-hiv-1-on-suppressive-art/

A5422: CH505 TF chTrimer Vaccination in Adults Living ... This study is looking to see if an investigational anti-HIV vaccine (stabilized CH505 TF chTrimer) is safe and well-tolerated in people living with HIV on ...

5. hividgm.ucsf.edu hividgm.ucsf.edu/safety-and-immunogenicity-stabilized-ch505-tf-chtrimer-vaccination-adults-living-hiv-1-suppressive

Safety and Immunogenicity of Stabilized CH505 TF chTrimer ... This study is looking to see if an investigational anti-HIV vaccine is safe and well-tolerated in people living with HIV.

6. ctv.veeva.com ctv.veeva.com/study/safety-and-immunogenicity-of-stabilized-ch505-tf-chtrimer-vaccination-in-adults-living-with-hiv-1-on

Safety and Immunogenicity of Stabilized CH505 TF chTrimer ... Safety and Immunogenicity of Stabilized CH505 TF chTrimer Vaccination in Adults Living With HIV-1 on Suppressive Antiretroviral Therapy.