HIV Vaccines for HIV

(CM HIV-CORE008 Trial)

No longer recruiting at 2 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new vaccines to determine if they can safely enhance the immune system's ability to combat HIV in individuals already on antiretroviral therapy. Participants will receive one of two experimental vaccines, C1C62-M3M4 or C62-M4, or a placebo to compare responses. It suits those living with HIV who are on stable antiretroviral treatment and have maintained a low viral load. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that both the C62-M4 and C1C62-M3M4 vaccine plans are generally safe for people with HIV on antiretroviral therapy. In earlier studies, participants tolerated these vaccines well, with no serious side effects reported. Most side effects were mild, such as soreness at the injection site or mild flu-like symptoms. These results suggest that the vaccines do not cause major health problems, indicating a good safety profile. However, as this is an early-phase study, the primary goal is to ensure the vaccines are safe for further testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these HIV vaccines because they employ a unique approach different from current antiretroviral therapies, which primarily focus on suppressing the virus. The C62-M4 and C1C62-M3M4 vaccines aim to stimulate the immune system to recognize and combat HIV, potentially providing long-lasting protection. These vaccines use viral vectors like ChAdOx1 and MVA to deliver HIV-specific antigens, which might train the immune system to fight the virus more effectively. This innovative strategy could lead to a preventive option that complements existing treatments and helps control the spread of HIV.

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

Research shows that the C62-M4 and C1C62-M3M4 vaccines, tested in this trial, are designed to strengthen the body's defense against HIV. Previous studies have found that these vaccines can safely boost the activity of T-cells, crucial immune cells that help fight HIV. Participants in this trial may receive the C62-M4 vaccine, known for its safety and lack of major side effects. Alternatively, they may receive the C1C62-M3M4 vaccine, which has triggered a wide-ranging immune response. These early results suggest that the vaccines might help the body better manage HIV. ^{1 5 6 7 8}

Who Is on the Research Team?

Cynthia L Gay, MD, MPH

Principal Investigator

University of North Carolina

Nilu Goonetilleke, PhD

Principal Investigator

University of North Carolina

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: C62-M4 Experimental Treatment 2 Interventions

ChAdOx1.HIVconsv62 (C62) vaccine administered at Day 0, followed by MVA.tHIVconsv4 (M4) vaccine administered at Day 28

Group II: C1C62-M3M4 Experimental Treatment 4 Interventions

ChAdOx1.tHIVconsv1 (C1) and ChAdOx1.HIVconsv62 (C62) vaccines administered at Day 0, followed by MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) vaccines administered at 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+

Published Research Related to This Trial

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05604209?tab=results

Safety and Immunogenicity of HIV-1 Vaccines C62-M4 or ... MVA.tHIVconsv4: Administered intramuscularly (IM) at Day 28. ChAdOx1.tHIVconsv1 (C1) and ChAdOx1.HIVconsv62 (C62) vaccines administered at Day 0, followed by ...

2. thelancet.com thelancet.com/journals/lanmic/article/PIIS2666-5247(24)00309-4/fulltext

Safety and broad immunogenicity of HIVconsvX conserved ... A double-blind, randomised, placebo-controlled phase 1 trial in healthy adults living without HIV-1 in eastern and southern Africa.

3. sciencedirect.com sciencedirect.com/science/article/pii/S266652472400209X

Safety and immunogenicity of the ChAdOx1–MVA-vectored ... We developed a T-cell immunogen-based bivalent mosaic vaccine, HIVconsvX, delivered by vaccine vectors ChAdOx1 and modified vaccinia Ankara.

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/09/NCT05604209/SAP_002.pdf

IGHID 12107 - A Phase I Study to Evaluate the Safety and ... This statistical analysis plan (SAP) details the statistical procedures that address the study objectives specified in Protocol version 3.0 ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39612921/

Safety and immunogenicity of the ChAdOx1-MVA-vectored ... Low-dose C1 was safe and well tolerated in group 1, and all three vaccine components were well tolerated in volunteer group 2. There were no serious adverse ...

6. thelancet.com thelancet.com/journals/lanmic/article/PIIS2666-5247(24)00209-X/fulltext

Safety and immunogenicity of the ChAdOx1–MVA-vectored ... The vaccine regimen consists of ChAdOx1.tHIVconsv1 (C1) plus ChAdOx1.HIVconsv62 (C62) prime and MVA.tHIVconsv3 (M3) plus MVA.tHIVconsv4 (M4) ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666524724003094

Safety and broad immunogenicity of HIVconsvX conserved ... In the HIV-CORE 006 trial, people living without HIV-1 in sub-Saharan Africa received either the vaccine regimen (C1-M3M4; n=72) or placebo (n=16) and were ...

8. clinicaltrial.be clinicaltrial.be/en/details/82302?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

Safety and Immunogenicity of HIV-1 Vaccines C62-M4 or ... IGHID 12107 - A Phase I Study to Evaluate the Safety and Immunogenicity of the ChAdOx1.HIVconsv62 - MVA.tHIVconsv4 (C62-M4) or, ChAdOx1.