AzTrials
AzTrials

Chronic HIV InfectionPhase 1NCT06006546

The Study of Immunization in People Living With HIV Undergoing an ATI for Elicitation of VRC01-lineage Antibodies

A Phase 1 study testing 426c.Mod.Core-C4b and Adjuvant 3M-052-AF+Alum in people with Chronic HIV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a multicenter controlled interventional trial. This phase 1 trial is the first study to assess 426c.Mod.Core-C4b adjuvanted with 3M-052-AF + aluminum hydroxide suspension (Alum) in people living with HIV (PLWH). Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Chronic HIV Infection
What is being tested?
426c.Mod.Core-C4b and Adjuvant 3M-052-AF+Alum
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
7 sitesUnited States
Study dates
3 Jan 2024to 12 Oct 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Able and willing to complete the informed consent process, including an Assessment of Understanding (AoU): Volunteer demonstrates an understanding of this study and completes a questionnaire prior to first vaccination with verbal demonstration of understanding of questionnaire items that were answered incorrectly.
  • 18 to 55 years old, inclusive, on day of enrollment.
  • Confirmed HIV infection as documented by medical records or confirmatory HIV testing at screening.
  • On suppressive ART for at least 48 weeks prior to screening. ART is defined as a combination therapy regimen including at least 1 integrase inhibitor and 1 nucleoside reverse transcriptase inhibitor (such as Dovato™) or 2 nucleoside reverse transcriptase inhibitors plus integrase inhibitors. Changes in ARVs for reasons other than virologic failure (eg, tolerability, simplification, different formulation, drug-drug interaction profile) are allowed within 48 weeks prior to screening and up until 6 weeks prior to screening. A fully active alternative ARV regimen is available, in the opinion of the Investigator, in the event of discontinuation of the current ARV regimen with development of resistance.
  • Plasma HIV RNA < 50 copies/mL (or lower limit of quantitation [LLOQ]) for at least 48 weeks prior to enrollment. NOTE: At least one viral load measurement within 48 weeks prior to the screening visit and another viral load from the screening prior to enrollment visit must be available for review. Two "blips" (ie, plasma HIV-1 RNA > LLOQ and < 400 copies/mL) are allowed if each blip is preceded and followed by values < LLOQ and if the blip(s) occur(s) more than 24 weeks prior to enrollment.
  • CD4+ cell count > 450 cells/mm3 and CD4+ cell % ≥ 15% obtained within 40 days prior to enrollment.
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  • Available for clinic follow-up through the last clinic visit, willing to undergo leukapheresis, and willing to be contacted 12 months after the last study-product administration.
  • Agrees not to enroll in another study of an investigational agent during participation in the trial. If a potential participant is already enrolled in another clinical trial, approvals from the other trial sponsor and the HVTN 807 PSRT are required prior to enrollment into HVTN 807.
  • In good general health according to the clinical judgment of the site investigator.
  • Physical examination and laboratory results without clinically significant findings that would interfere with assessment of safety or reactogenicity in the clinical judgement of the site investigator.
  • Total serum calcium of ≥ 8.5 mg/dL.
  • Hemoglobin (Hgb):
  • ≥ 10.0 g/dL for volunteers who were assigned female sex at birth (AFAB)
  • ≥ 11.0 g/dL for cisgender volunteers who were assigned male sex at birth (AMAB) and for transgender men who have been on hormone therapy for more than 6 consecutive months
  • ≥ 11.0 g/dL for transgender women who have been on hormone therapy for more than 6 consecutive months
  • For transgender volunteers who have been on hormone therapy for less than 6 consecutive months, determine Hgb eligibility based on their sex assigned at birth.
  • Absolute neutrophil count (ANC) ≥ 750/mm3
  • .
  • Platelets ≥ 100,000/mm3
  • .
  • Alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN) based on the institutional normal range and direct bilirubin within the institutional range of normal.
  • Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2 as calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation.
  • For Group 1 volunteers: must agree to consistently use condoms from study week 14 through until viral load post-ATI is undetectable (at a minimum 20 weeks on study, at a maximum 64 weeks on study).
  • For Group 1 volunteers
  • Persons of pregnancy potential
  • Must have a negative beta human chorionic gonadotropin (β-HCG) pregnancy test (urine or serum) on day of enrollment.
  • Must agree to use effective means of contraception from at least 21 days prior to enrollment until at least 8 weeks post last vaccination and viral load post-ATI is undetectable (at a minimum 20 weeks on study, at a maximum 64 weeks on study).
  • Volunteers who are AFAB or intersex at birth must agree to not seek pregnancy through alternative methods, such as oocyte retrieval, artificial insemination, or in vitro fertilization from at least 21 days prior to enrollment through until viral load post-ATI is undetectable (at a minimum 20 weeks on study, at a maximum 64 weeks on study).
  • For Group 2 volunteers
  • Persons of pregnancy potential:
  • Must have a negative β-HCG pregnancy test (urine or serum) on day of enrollment.
  • Must agree to use effective means of contraception from at least 21 days prior to enrollment until 8 weeks after their last scheduled vaccination (study week 20).
  • Volunteers who are AFAB or intersex at birth must agree to not seek pregnancy through alternative methods, such as oocyte retrieval, artificial insemination, or in vitro fertilization from at least 21 days prior to enrollment through 8 weeks after their last scheduled vaccination timepoint.

Who cannot join

  • Current receipt of ART other than nucleoside reverse transcriptase inhibitor and integrase inhibitor.
  • Receipt of long-acting ART within 3 months of enrollment.
  • Documented history of resistance to any components of the current ARV regimen.
  • Known resistance to 1 or more drugs in 2 or more ARV drug classes. NOTE: M184V/I is an exception and should not be considered when assessing this criterion. Prior HIV resistance testing is not required.
  • ART initiation during acute HIV-1 infection (defined as within 1 year of HIV-1 acquisition, if known).
  • History of an HIV-associated malignancy (including Kaposi's sarcoma), and any type of lymphoma or virus-associated cancers.
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  • History of HIV-associated neurocognitive disease or progressive multifocal leukoencephalopathy.
  • History of HIV-related illness under US Centers for Disease Control (CDC) Category C (except for recurrent pneumonia) within 10 years prior to screening, based on available medical history and assessed by the Investigator for clinical relevance. Anyone with a history of CD4 < 200 cells/mm3 on one or more occasions, based on available medical history and assessed by the Investigator for clinical relevance. Documentation of every case with history of CD4 < 200 cells/mm3 must be provided to the Sponsor and PSRT, who will determine eligibility on a case-by-case basis. NOTE: History of treated and resolved pulmonary tuberculosis (TB) will not be exclusionary.
  • Active or recent non-HIV-associated malignancy requiring systemic chemotherapy or surgery within 36 months prior to enrollment or for whom such therapies are expected in the subsequent 12 months. NOTE: Minor surgical removal of localized skin cancers (squamous cell carcinoma, basal cell carcinoma) is not exclusionary.
  • Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg), hepatitis C antibody without documented history of prior treatment and clearance, or hepatitis C virus RNA (HCV-RNA) in blood.
  • Diagnosis of cirrhosis.
  • Current untreated or incompletely treated active TB disease or untreated latent TB infection. NOTE: Individuals who are on treatment for latent TB with at least 4 weeks of treatment completed are not excluded.
  • Volunteer who is breastfeeding or pregnant.
  • Body mass index (BMI) ≥ 40. Enrollment of individuals with BMI ≥ 40, whom the site investigator assesses are in good health, may be considered by PSRT approval.
  • Diabetes mellitus (DM). Type 2 DM controlled with diet alone (and confirmed by HgbA1c ≤ 8% within the last 6 months) or a history of isolated gestational diabetes are not exclusionary. Enrollment of individuals with Type 2 DM that is well controlled on hypoglycemic agent(s) may be considered by the PSRT on a case-by-case basis
  • History of or current clinical atherosclerotic cardiovascular disease (ASCVD), as defined by 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, including a previous diagnosis of any of the following:
  • Acute myocardial infarction
  • Acute coronary syndromes
  • Stable or unstable angina
  • Coronary or other arterial revascularization
  • Stroke
  • Transient ischemic attack
  • Peripheral arterial disease presumed to be of atherosclerotic origin
  • Previous or current recipient of an investigational HIV vaccine (previous placebo/control recipients are not excluded).
  • Receipt of non-HIV experimental vaccine(s) received within the last 1 year. Exceptions include vaccines that have subsequently undergone licensure or Emergency Use Authorization (EUA) by the FDA or World Health Organization (WHO) emergency use listing (EUL), or if outside the US, by the national Regulatory Authority (RA) authorizing this clinical trial.
  • Congenital or acquired immunodeficiency, including systemic medication use likely to impair immune response to vaccine in the opinion of the site investigator, such as history of systemic corticosteroids (long-term use), immunosuppressive anti-cancer or other immunosuppressive agents, interleukins, systemic interferons, systemic chemotherapy, or other medications considered significant by the investigator within the 24 weeks prior. Note: HIV is not exclusionary.
  • Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires PSRT approval.
  • Previous receipt of any anti-HIV monoclonal antibody.
  • Receipt of any of the following vaccines within 4 weeks prior to enrollment:
  • Live replicating vaccines
  • Any mRNA-based vaccine with FDA licensure, FDA EUA, or WHO EUL
  • ACAM2000 vaccine > 30 days prior with a vaccination scab still present.
  • Receipt of any vaccines that are not covered in #22 above within 14 days prior to enrollment. Please note this includes replication incompetent vaccines such as the Jynneos vaccine for the prevention of mpox (formerly known as monkeypox) disease.
  • Initiation of antigen-based immunotherapy (AIT) for allergies within the previous year (stable immunotherapy is not exclusionary); inclusion of participants who initiated immunotherapy within the previous year requires PSRT approval. Note: Any AIT should be scheduled at least 14 days prior to enrollment.
  • Receipt of investigational research agents with a half-life of 7 or fewer days within 4 weeks prior to enrollment. If a potential participant has received investigational agents with a half-life of greater than 7 days (or unknown half-life) within the past year, PSRT approval is required for enrollment.
  • History of serious reaction (eg, hypersensitivity, anaphylaxis) to any vaccine or component of the study vaccine, including imidazoquinolone (eg, imiquimod).
  • Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
  • Idiopathic urticaria within the past year.
  • Bleeding disorder diagnosed by a clinician which would make study procedures a contraindication (eg, factor deficiency, coagulopathy, platelet disorder requiring special precautions).
  • Seizure disorder; febrile seizures as a child or seizures secondary to alcohol withdrawal more than 5 years ago are not exclusionary.
  • Asplenia or functional asplenia.
  • Active duty and reserve US military personnel.
  • Any other chronic or clinically significant condition that, in the clinical judgment of the investigator, would jeopardize the safety or rights of the study participant, including but not limited to: clinically significant forms of substance use or alcohol use disorder(s), serious psychiatric disorders, persons with any suicide attempt within the past 1 year (if between 1 and 2 years, consult PSRT for approval), or cancer that, in the clinical judgement of the site investigator, has potential for recurrence (excluding basal cell carcinoma).
  • A participant with a history of a potential immune-mediated medical condition (PIMMC), either active or remote. Specific examples are listed in Appendix I (AESI Index). Not exclusionary: 1) Remote history of Bell's palsy (> 2 years ago) not associated with other neurologic symptoms and 2) mild psoriasis that does not require ongoing systemic treatment.
  • Investigator concern for difficulty with venous access based on clinical history and physical examination. For example, persons with a history of intravenous drug use or substantial difficulty with previous blood draws.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • The Ponce de Leon Center CRS (Site # 5802)

    Atlanta, Georgia, 30303

  • Alabama CRS (Site # 31788)

    Birmingham, Alabama, 35294-2170

  • BIDMC VCRS (Site # 32077)

    Boston, Massachusetts, 02215

  • The Hope Clinic of the Emory Vaccine Center CRS (Site #31440)

    Decatur, Georgia, 30030

  • Columbia P&S CRS (Site # 30329)

    New York, New York, 10032

  • University of Pittsburg CRS (Site # 1001)

    Pittsburgh, Pennsylvania, 15213

  • Seattle Vaccine and Prevention CRS (Site # 30331)

    Seattle, Washington, 98104

Other trials in United States

About this study

Official title: 426c.Mod.Core-C4b Adjuvanted With 3M-052-AF + Alum Immunization in Combination With an Antiretroviral Analytical Treatment Interruption (ATI) in People Living With HIV for Elicitation of VRC01-lineage Antibodies

This is a multicenter controlled interventional trial. This phase 1 trial is the first study to assess 426c.Mod.Core-C4b adjuvanted with 3M-052-AF + aluminum hydroxide suspension (Alum) in people living with HIV (PLWH).

Read the detailed description

The aim of this study is to combine the ability of germline (GL)-targeting HIV-1 Envelope protein (Env)-derived immunogens to activate naïve B cells that express the unmutated GL forms of VRC01-class broadly neutralizing antibodies (bnAbs) with the booster capabilities of viral Envs that are expected to circulate in persons living with chronic HIV. The goals are: 1) to elicit VRC01-class GL and intermediate stage antibody responses in PLWH; 2) to identify the viral Envs that guided the maturation of the GL-VRC01 responses elicited by the GL-targeting Env immunogen; 3) during the time when viremia is detectable, the investigator will assess the stage of maturation of these VRC01 antibodies and if they affect viral replication; and 4) investigate how the virus may evolve to escape the activity of these antibodies.

Being tested
426c.Mod.Core-C4b, Adjuvant 3M-052-AF+Alum

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 426c.Mod.Core-C4bBiological

    100 mcg and 300 mcg

  • Adjuvant 3M-052-AF+AlumOther

    5 mcg

Study groups in NCT06006546
Study groupRoleWhat they receive
Group 1 (ATI)ExperimentalGroup 1 will receive 2 doses of the vaccine at Week 0 and 12. Group 1 will transition to Schedule 2 at the Week 14 visit. The Schedule 2 "ATI with Monitoring" phase can last for 24 weeks OR until any antiretroviral therapy (ART) re-initiation criteria are met, OR the ATI can continue longer with the approval of the Protocol Safety Review Team (PSRT) and the participant's primary HIV healthcare provider. Group 1 will transition to Schedule 3, the "Follow-up on ART restart" phase that lasts until study week 64, regardless of the point where it begins.
Receives: Biological: 426c.Mod.Core-C4b; Other: Adjuvant 3M-052-AF+Alum
Group 2 (No ATI) ControlExperimentalGroup 2 transitions from Schedule 1 into Schedule 4, "Follow-up on ART," at the Week 14 visit, and remains on Schedule 4 through study week 64.
Receives: Biological: 426c.Mod.Core-C4b; Other: Adjuvant 3M-052-AF+Alum

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The number of participants local reactogenicity signs and symptoms

    Measured: 14 days following each vaccination

  2. The number of participants systemic reactogenicity signs and symptoms

    Measured: 14 days following each vaccination

  3. Number and description of serious adverse events (SAEs)

    adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult AEs

    Measured: 12 months following any receipt of study product

  4. Number and description of medically attended adverse events (MAAEs)

    adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult AEs

    Measured: 12 months following any receipt of study product

  5. Number and description of adverse events of special interest (AESIs)

    adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult AEs

    Measured: 12 months following any receipt of study product

  6. Number and description of AEs leading to early participant withdrawal or permanent discontinuation and reason for withdrawal/discontinuation

    adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult AEs

    Measured: 12 months following any receipt of study product

  7. Frequency of total Env-specific and CD4-bs-specific B cells, prior to ATI

    as assessed by flow cytometry at baseline and after each vaccination

    Measured: At baseline (week 0) and after each vaccination

  8. Frequency of VRC01-class BCR sequences of isolated CD4-bs B cells, prior to ATI

    , as assessed by B-cell sorting and BCR sequencing

    Measured: At baseline (week 0) and after each vaccination

  9. Frequency of Env-specific and CD4-bs-specific B cells

    as assessed by flow cytometry

    Measured: After week 16

  10. Frequency of VRC01-class BCR sequences of isolated CD4-bs B cells

    as assessed by B-cell sorting and BCR sequencing

    Measured: After week 16

Secondary outcomes (3)

  1. Compare Env sequences during ATI in Group 1 participants that initiated the development of VRC01 antibodies and those that did not

    Measured: Study duration or 12 months following any receipt of study product

  2. Magnitude of Binding of selected recEnvs from Group 1 participants that initiated the development of VRC01-class antibodies to VRC01-class precursor and intermediate antibodies

    Measured: Study duration or 12 months following any receipt of study product

  3. Magnitude of Binding of selected recEnvs from Group 1 participants that initiated the development of VRC01-class antibodies to B cells expressing VRC01-class BCRs.

    Measured: Study duration or 12 months following any receipt of study product

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Aug 2023
  2. Study start3 Jan 2024
  3. Primary completion12 Oct 2026
  4. Study completion12 Oct 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06006546
Sponsor's protocol ID
HVTN 807
Other IDs
39013
Status last verified
Nov 2026
First submitted
17 Aug 2023
Last updated
6 Nov 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 426c.Mod.Core-C4b and Adjuvant 3M-052-AF+Alum in people with Chronic HIV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 45 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The number of participants local reactogenicity signs and symptoms (time frame: 14 days following each vaccination). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06006546.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.

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