HIV Vaccines for HIV

(CM HIV-Core008 Trial)

Recruiting at 1 trial location

Overseen By Cindy L Gay, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of North Carolina, Chapel Hill

Must be taking: Antiretrovirals

Must not be taking: Immunomodulators, Corticosteroids

Disqualifiers: Pregnancy, Syphilis, HCV, others

Compensation: Varies

Number of Visits: 13

Duration: 4 weeks

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing two vaccines given as muscle injections to people with HIV who are already on treatment. The goal is to see if these vaccines are safe and if they can help the immune system better fight the virus. Participants will receive the injections and be monitored for any reactions.

Will I have to stop taking my current medications?

The trial does not specify that you need to stop taking your current medications, but you must continue your antiretroviral therapy (ART) throughout the study. There should be no changes in your ART medication 30 days before screening.

What data supports the effectiveness of the treatment C1C62-M3M4, C62-M4 for HIV?

Research shows that certain HIV vaccines can trigger strong immune responses, such as CD4+ T-cell responses, which are important for controlling HIV. Additionally, some vaccine regimens have been effective in producing antibodies that can target multiple HIV strains, suggesting potential for broad protection. ^{1 2 3 4 5}

Is the HIV vaccine safe for humans?

Research on various HIV vaccines, including those tested in over 1500 healthy people, shows they are generally well tolerated with no serious long-term safety issues. Some studies reported mild to moderate side effects, but no significant safety problems were found in most trials. ^{6 7 8 9 10}

How does the treatment C1C62-M3M4, C62-M4 for HIV differ from other treatments?

The treatment C1C62-M3M4, C62-M4 is unique because it involves a vaccine approach that aims to induce strong immune responses specifically targeting HIV, potentially increasing the body's ability to control the virus. This differs from standard antiretroviral therapies, which primarily focus on suppressing viral replication rather than enhancing the immune system's ability to fight the virus. ^{1 2 11 12 13}

Research Team

Cindy L Gay, MD, MPH

Principal Investigator

University of North Carolina

Nilu Goonetilleke, PhD

Principal Investigator

University of North Carolina

Eligibility Criteria

This trial is for adults aged 18-70 with HIV, on stable ART with undetectable viral load and CD4 count >=350. They must be willing to follow the study plan, have no recent serious illness or hospitalization, not pregnant or planning pregnancy, and agree to use birth control. Excluded are those with certain medical conditions, prior adenovirus vaccines including COVID-19 ones, live vaccines within 60 days, untreated syphilis or HCV treatment recently.

Inclusion Criteria

Able and willing to give written informed consent

Able and willing to comply with all study requirements through D196 Week 28

All women must have a negative serum pregnancy test at screening

Exclusion Criteria

I have a bleeding disorder or am on long-term blood thinners.

Women of childbearing age/potential who are breast feeding, pregnant, or planning pregnancy from enrollment to 4 months after the last vaccination at D28, D196

Untreated syphilis infection defined as a positive rapid plasma reagin (RPR) without clear documentation of treatment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the C62-M4 or C1C62-M3m4 vaccine or a placebo on Day 0 and Day 28

4 weeks

2 visits (in-person)

Monitoring

Participants are monitored for safety and immune response, including 11 non-vaccination visits and 6 phone visits

7 months

11 visits (in-person), 6 visits (phone)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• C1C62-M3M4
• C62-M4

Trial Overview The trial tests if C62-M4 or C1C62-M3M4 vaccines are safe in HIV-positive individuals on ART and whether they boost immune responses against HIV. Participants will receive intramuscular injections of either vaccine formulation or a placebo and their T cell responses will be monitored.

Participant Groups

Group I: C62 Experimental Treatment 2 Interventions

C62 administered at Day 0 and M4 on Day 28

Group II: C1C62 Experimental Treatment 2 Interventions

C1C62 administered at Day 0 and M3M4 on Day 28

Group III: Placebo Placebo Group 1 Intervention

Placebo administered on Day 0 and Day 28

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Findings from Research

Over 1500 healthy individuals have participated in studies of HIV-1 vaccines, which have shown good safety profiles with no serious toxicity reported, indicating that these vaccines are well tolerated.

Candidate vaccines, particularly those using gp120 and vaccinia vectors, successfully induce immune responses, including neutralizing antibodies and cytotoxic T cell activity, although they currently only neutralize laboratory-adapted HIV-1 strains, not primary isolates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human studies in the development of human immunodeficiency virus vaccines. Dolin, R.[2019]

A phase 1 trial involving 36 healthy participants demonstrated that shorter, 6-month regimens of a mosaic HIV-1 vaccine elicited strong immune responses comparable to a longer, 12-month regimen, suggesting they could be effective for HIV prevention.

All vaccine regimens were well tolerated, with mild-to-moderate side effects reported, indicating a favorable safety profile, which is crucial for community-level vaccine delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of shortened mosaic HIV-1 vaccine schedules: a randomised, double-blind, placebo-controlled phase 1 trial (IPCAVD010/HPX1002) and a preclinical study in rhesus monkeys (NHP 17-22). Stephenson, KE., Wegmann, F., Tomaka, F., et al.[2021]

References

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

Induction of strong HIV-1-specific CD4+ T-cell responses using an HIV-1 gp120/NefTat vaccine adjuvanted with AS02A in antiretroviral-treated HIV-1-infected individuals. [2021]

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

An adenovirus-based HIV subtype B prime/boost vaccine regimen elicits antibodies mediating broad antibody-dependent cellular cytotoxicity against non-subtype B HIV strains. [2020]

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

Randomised trial of MNrgp120 HIV-1 vaccine in symptomless HIV-1 infection. [2019]

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

Immunogenicity of a recombinant measles HIV-1 subtype C vaccine. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Progress towards an HIV-1 subtype C vaccine. [2005]

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

Long-term safety analysis of preventive HIV-1 vaccines evaluated in AIDS vaccine evaluation group NIAID-sponsored Phase I and II clinical trials. [2019]

7. England pubmed.ncbi.nlm.nih.gov

HIV therapeutic vaccine enhances non-exhausted CD4+ T cells in a randomised phase 2 trial. [2020]

8. England pubmed.ncbi.nlm.nih.gov

The aftermath of the Merck's HIV vaccine trial. [2021]

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

Safety of 2 recombinant human immunodeficiency virus type 1 (HIV-1) envelope vaccines in neonates born to HIV-1-infected women. [2013]

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

Human studies in the development of human immunodeficiency virus vaccines. [2019]

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

Cellular immune responses in asymptomatic human immunodeficiency virus type 1 (HIV-1) infection and effects of vaccination with recombinant envelope glycoprotein of HIV-1. [2018]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of shortened mosaic HIV-1 vaccine schedules: a randomised, double-blind, placebo-controlled phase 1 trial (IPCAVD010/HPX1002) and a preclinical study in rhesus monkeys (NHP 17-22). [2021]

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

An HIV Vaccine Targeting the V2 Region of the HIV Envelope Induces a Highly Durable Polyfunctional Fc-Mediated Antibody Response in Rhesus Macaques. [2021]