HIVPhase 1NCT06796686
Clinical Trial to Evaluate the Safety and Immunogenicity of a Priming Regimen of 426c.Mod.Core-C4b Followed by HxB2.WT.Core-C4b Boosts, Both Adjuvanted With 3M-052 AF + Alum, in Adult Participants Without HIV and in Overall Good Health
A Phase 1 study testing 426c.Mod.Core-C4b, HxB2.WT.Core-C4b and 3M-052-AF adjuvant in people with HIV, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 sites in United States.
Trial summary
This is a partially randomized, open-label phase 1 study to evaluate the safety and immunogenicity of a priming regimen of 426c.Mod.Core-C4b adjuvanted with 3M-052 AF + Alum followed by boosts with HxB2.WT.Core-C4b adjuvanted with 3M-052 AF + Alum. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV
- What is being tested?
- 426c.Mod.Core-C4b, HxB2.WT.Core-C4b and 3M-052-AF adjuvant
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 6 sitesUnited States
- Study dates
- 17 Mar 2025to 15 Jan 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Healthy volunteers accepted
- Adult
Who may be able to join
- Demonstrates an understanding of the study and is able and willing to complete the informed consent process.
- 18 to 55 years old, inclusive, on day of enrollment.
- Available for clinic follow-up through the last clinic visit, willing to undergo leukapheresis, and willing to be contacted after the last study-product administration, including for potential participation in additional studies.
- 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 320 PSRT are required prior to enrollment into HVTN 320.
- 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 judgment of the site investigator.
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- Agrees to discuss their potential for HIV acquisition and agrees to prevention counseling.
- Hemoglobin (Hgb):
- ≥11.0 g/dL for AFAB volunteers
- ≥13.0 g/dL for cisgender AMAB volunteers or for volunteers who have been on masculinizing hormone therapy for more than 6 consecutive months
- ≥12.0 g/dL for AMAB volunteers who have been on feminizing hormone therapy for more than 6 consecutive months
- For volunteers who have been on gender-affirming hormone therapy for less than 6 consecutive months, determine Hgb eligibility based on their sex assigned at birth.
- White blood cell (WBC) count = 2,500 to 12,000/mm3 (WBC over 12,000/mm3 is not exclusionary if further evaluation shows general good health and if PSRT approval is granted).
- Platelets = 125,000 to 550,000/mm3.
- Alanine aminotransferase (ALT) < 2.5 × upper limit of institutional reference range.
- Serum creatinine ≤ 1.1 × upper limit of normal (ULN) based on the institutional normal range.
- Corrected total serum calcium level of ≥ 8.5 mg/dL. "Corrected" includes measurement of serum albumin.
- Systolic blood pressure of 90 to < 140 mmHg and diastolic blood pressure of 50 to < 90 mmHg at screening visit. The average blood pressure between the screening visit and the enrollment visit must be below 140 mmHg systolic and 90 mmHg diastolic. A single measurement ≥ 160 systolic mmHg or 100 mmHg diastolic during the current study evaluation is exclusionary.
- Negative HIV test results by one of the following options:
- US Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA)
- Chemiluminescent microparticle immunoassay (CMIA)
- Two negative results on HIV rapid tests (one of which must be FDA-approved CMIA)
- Negative for anti-hepatitis C virus (HCV) Abs (anti-HCV) or negative HCV nucleic acid test (NAT) if anti-HCV Abs are detected.
- Negative for hepatitis B surface antigen (HBsAg).
- For AFAB or intersex at birth volunteers who are capable of becoming pregnant (hereafter referred to as "persons of pregnancy potential"):
- Must agree to use effective means of contraception from at least 21 days prior to enrollment through 8 weeks after their last scheduled vaccination timepoint.
- Must have a negative beta human chorionic gonadotropin (β-HCG) pregnancy test (urine or serum) on day of enrollment.
- Note: Persons who are NOT of pregnancy potential due to total hysterectomy or bilateral oophorectomy (verified by medical records) or menopause (no menses for ≥1 year) are not required to undergo pregnancy testing.
- AFAB or intersex at birth volunteers 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
- Volunteer who is breastfeeding/chestfeeding 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, provided that the HgbA1c is ≤ 8% within the last 6 months (sites may draw these at screening).
- Previous or current recipient of an investigational HIV vaccine (previous placebo/control recipients are not excluded).
- Receipt of non-HIV investigational 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 glucocorticoid use, ≥ prednisone 10 mg/day within 3 months prior to enrollment.
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- 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 VRC01 mAb or other CD4bs mAbs.
- Receipt of any of the following within 4 weeks prior to enrollment:
- Live replicating vaccine
- Any mRNA-based vaccine with FDA licensure, FDA EUA, or WHO EUL
- ACAM2000 vaccine > 28 days prior with a vaccination scab still present.
- Receipt of any vaccine that is not covered in exclusion criterion #9 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 for allergies within the previous year (stable immunotherapy is not exclusionary); inclusion of participants who initiated immunotherapy within the previous year requires PSRT approval.
- 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 more 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 related vaccine or component of the study-vaccine regimen (eg, imiquimod).
- Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
- Idiopathic urticaria within the past year.
- Bleeding disorder diagnosed by a clinician that would make study procedures a contraindication.
- History of seizure(s) within the past 3 years. Also exclude if volunteer has used medications to prevent or treat seizure(s) at any time within the past 3 years.
- 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, hinder their ability to participate in the study, or affect their immune responses to study products. Such conditions include but are not limited to clinically significant forms of substance use or alcohol use disorder(s), serious psychiatric disorders, any suicide attempt within the past 1 year (if between 1 and 2 years, consult PSRT for approval), or cancer that, in the clinical judgment of the site investigator, has potential for recurrence (excluding basal cell carcinoma).
- Asthma is excluded if the participant has ANY of the following:
- Required either oral or parenteral corticosteroids for an exacerbation 2 or more times within the past year; OR
- Needed emergency care, urgent care, hospitalization, or intubation for an acute asthma exacerbation within the past year (eg, would NOT exclude individuals with asthma who meet all other criteria but sought urgent/emergent care solely for asthma medication refills or coexisting conditions unrelated to asthma); OR
- Uses a short-acting rescue inhaler more than 2 days per week for acute asthma symptoms (ie, not for preventive treatment prior to athletic activity); OR
- Uses medium- to high-dose inhaled corticosteroids (> 250 mcg fluticasone or therapeutic equivalent per day), whether in single-therapy or dual-therapy inhalers (ie, with a long-acting beta agonist [LABA]); OR
- Uses more than 1 medication for maintenance therapy daily. Inclusion of anyone on a stable dose of more than 1 medication for maintenance therapy daily for greater than 2 years requires PSRT approval.
- A participant with a history of a PIMMC, either active or remote. Not exclusionary: (1) remote history of Bell's palsy (> 2 years ago) not associated with other neurologic symptoms and (2) mild psoriasis or other mild, uncomplicated, localized or dermatologic condition that does not require ongoing systemic treatment.
- History of allergy to local anesthetic (Novocaine, Lidocaine).
- Investigator concern for difficulty with venous access based on clinical history and physical examination. For example, persons with a history of intravenous (IV) drug use or substantial difficulty with previous blood draws.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
United States6 sites, 5 recruiting
- Not yet recruiting
Ponce de Leon Center CRS
Atlanta, Georgia, 30308
Ericka Patrick, RN, MSN, 404-616-6313, erpatri@emory.edu
- Recruiting
Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
Boston, Massachusetts, 02115
Jose Licona, 617-525-9433, jlicona@partners.org
- Recruiting
The Hope Clinic of the Emory Vaccine Research Center; Emory University
Decatur, Georgia, 30030
Emily Osbourne, 404-712-1370, emily.claire.osborne@emory.edu
- Not yet recruiting
Columbia Physicians & Surgeons
New York, New York, 10032
Anyelina Cantos, 212-305-2201, ac4314@cumc.columbia.edu
- Withdrawn
NY Blood Center CRS
New York, New York, 10065
- Not yet recruiting
Bridge HIV, San Francisco Department of Public Health
San Francisco, California, 94102
Emily Schaeffer, 628-217-7456, emily.schaeffer@sfdph.org
About this study
Official title: A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of a Priming Regimen of 426c.Mod.Core-C4b Followed by HxB2.WT.Core-C4b Boosts, Both Adjuvanted With 3M-052 AF + Alum, in Adult Participants Without HIV and in Overall Good Health
This is a partially randomized, open-label phase 1 study to evaluate the safety and immunogenicity of a priming regimen of 426c.Mod.Core-C4b adjuvanted with 3M-052 AF + Alum followed by boosts with HxB2.WT.Core-C4b adjuvanted with 3M-052 AF + Alum.
The primary hypothesis is that the boosting with HxB2.WT.Core-C4b adjuvanted with 3M-052 AF + Alum will further mature broadly neutralizing antibody (bnAb)-precursor B-cell lineages elicited by 426c.Mod.Core-C4b adjuvanted with 3M-052 AF + Alum.
426c.Mod.Core-C4b adjuvanted with 3M-052 AF + Alum has been tested in HVTN 301 previously, whereas the HxB2.WT.Core-C4b will be first-in-human (FIH).
- Conditions
- HIV
- Being tested
- 426c.Mod.Core-C4b, HxB2.WT.Core-C4b, 3M-052-AF adjuvant, Aluminum hydroxide suspension (Alum) adjuvant, Diluent
- Keywords
- HIV Infection
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
426c.Mod.Core-C4bBiological
426c.Mod.Core-C4b is supplied at a concentration of 2 mg/mL, 0.55 mL per vial.
HxB2.WT.Core-C4bBiological
HxB2.WT.Core-C4b is supplied at a concentration of 1 mg/mL, 0.5 mL per vial
3M-052-AF adjuvantBiological
immune response modifier (IRM)
Aluminum hydroxide suspension (Alum) adjuvantOther
Alhydrogel.
DiluentOther
Tris-NaCl buffer
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Active comparator | One fractional dose of 426c.Mod.Core-C4b and two bolus doses of HxB2.WT.Core-C4b Receives: Biological: 426c.Mod.Core-C4b; Biological: HxB2.WT.Core-C4b; Biological: 3M-052-AF adjuvant; Other: Aluminum hydroxide suspension (Alum) adjuvant; Other: Diluent |
| Group 2A | Active comparator | One fractional dose and one bolus dose of 426c.Mod.Core-C4b two bolus doses of HxB2.WT.Core-C4b Receives: Biological: 426c.Mod.Core-C4b; Biological: HxB2.WT.Core-C4b; Biological: 3M-052-AF adjuvant; Other: Aluminum hydroxide suspension (Alum) adjuvant; Other: Diluent |
| Group 2B | Active comparator | One split dose and one bolus of 426c.Mod.Core-C4b and two bolus doses of HxB2.WT.Core-C4b Receives: Biological: 426c.Mod.Core-C4b; Biological: HxB2.WT.Core-C4b; Biological: 3M-052-AF adjuvant; Other: Aluminum hydroxide suspension (Alum) adjuvant; Other: Diluent |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Local Signs and Symptoms within 14 Days Post-Vaccination
Measured: Within 14 days of receiving study vaccine
Incidence of Systemic Reactogenicity Signs and Symptoms within 14 Days Post-Vaccination
Measured: Within 14 days of receiving study vaccine
Incidence of Serious Adverse Events Over 52 Weeks Post-Vaccination
Measured: throughout the study and for 52 weeks following any receipt of the study product
Incidence of Medically Attended Adverse Events Over 52 Weeks Post-Vaccination
Measured: throughout the study and for 52 weeks following any receipt of the study product
Incidence of Adverse Events of Special Interest Over 52 Weeks Post-Vaccination
Measured: throughout the study and for 52 weeks following any receipt of the study product
Incidence of Adverse Events Leading to Withdrawal or Discontinuation Over 52 Weeks Post-Vaccination
Measured: throughout the study and for 52 weeks following any receipt of the study product
Frequency of CD4-bs-specific B cells before and approximately 12 weeks after each HxB2.WT.Core-C4b boost
assessed by flow cytometry
Measured: 12 weeks after each HxB2.WT.Core-C4b boost
Evolution of CD4-bs-Specific BCRs Before and 12 Weeks After Each HxB2.WT.Core-C4b Boost
Assessed by VH/VL Sequencing of Sorted B Cells
Measured: 12 Weeks After Each HxB2.WT.Core-C4b Boost
Secondary outcomes (39)
Response rate of serum antibodies at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost
will be assessed against a panel of autologous, precursor-sensitive, and heterologous viruses as measured by TZM-bl assay
Measured: 2 weeks after each HxB2.WT.Core-C4b boost
Potency of serum antibodies at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost
will be assessed against a panel of autologous, precursor-sensitive, and heterologous viruses as measured by TZM-bl assay
Measured: 2 weeks after each HxB2.WT.Core-C4b boost
Neutralizing breadth of serum antibodies at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost
will be assessed against a panel of autologous, precursor-sensitive, and heterologous viruses as measured by TZM-bl assay
Measured: 2 weeks after each HxB2.WT.Core-C4b boost
Response rate of Env-specific serum IgG binding antibodies will be assessed at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost
Measured: 2 weeks after each HxB2.WT.Core-C4b boost
Magnitude of Env-specific serum IgG binding antibodies will be assessed at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost
Measured: 2 weeks after each HxB2.WT.Core-C4b boost
Epitope specificity of Env-specific serum IgG binding antibodies will be assessed at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost
Measured: 2 weeks after each HxB2.WT.Core-C4b boost
Breadth of Env-specific serum IgG binding antibodies will be assessed at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost
Measured: 2 weeks after each HxB2.WT.Core-C4b boost
Magnitude of binding of Env-specific IgG binding antibodies
Measured: 2 weeks after each HxB2.WT.Core-C4b boost
Epitope specificity of Env-specific IgG binding antibodies
Measured: 2 weeks after each HxB2.WT.Core-C4b boost
Breadth of Env-specific IgG binding antibodies
Measured: 2 weeks after each HxB2.WT.Core-C4b boost
Potency of neutralizing antibodies
as measured by TZM-bl assay
Measured: 2 weeks after each HxB2.WT.Core-C4b boost
Breadth of neutralizing antibodies
as measured by TZM-bl assay
Measured: 2 weeks after each HxB2.WT.Core-C4b boost
Response rate of Env-specific serum IgG binding antibodies
Measured: at week 6 (visit 3) and week 17 (visit 5)
Magnitude of Env-specific serum IgG binding antibodies
Measured: at week 6 (visit 3) and week 17 (visit 5)
Epitope specificity of Env-specific serum IgG binding antibodies
Measured: at week 6 (visit 3) and week 17 (visit 5)
Breadth of Env-specific serum IgG binding antibodies
Measured: at week 6 (visit 3) and week 17 (visit 5)
Response rate of neutralizing antibodies
as measured by TZM-bl assay
Measured: at week 6 (visit 3) and week 17 (visit 5)
Potency of neutralizing antibodies
as measured by TZM-bl assay
Measured: at week 6 (visit 3) and week 17 (visit 5)
Breadth of neutralizing antibodies
as measured by TZM-bl assay
Measured: at week 6 (visit 3) and week 17 (visit 5)
Frequency of CD4-bs-specific B cells
as measured by flow cytometry
Measured: at week 15 (visit 4, prior to vaccination 2) and week 27 (visit 6, prior to vaccination 3)
Evolution of CD4-bs-specific BCRs
assessed by VH/VL sequencing of sorted B cells
Measured: at week 15 (visit 4, prior to vaccination 2)
Response rate of Env-specific serum IgG binding antibodies
Measured: at approximately 4 weeks post the first prime (visit 3) and week 17 (visit 5)
Magnitude of Env-specific serum IgG binding antibodies
Measured: at approximately 4 weeks post the first prime (visit 3) and week 17 (visit 5)
Epitope specificity of Env-specific serum IgG binding antibodies
Measured: at approximately 4 weeks post the first prime (visit 3) and week 17 (visit 5)
Breadth of Env-specific serum IgG binding antibodies
Measured: at approximately 4 weeks post the first prime (visit 3) and week 17 (visit 5)
Response rate of neutralizing antibodies
as measured by TZM-bl assay
Measured: at approximately 4 weeks post the first prime (visit 3) week 17 (visit 5)
Potency of neutralizing antibodies
as measured by TZM-bl assay
Measured: at approximately 4 weeks post the first prime (visit 3) week 17 (visit 5)
Breadth of neutralizing antibodies
as measured by TZM-bl assay
Measured: at approximately 4 weeks post the first prime (visit 3) week 17 (visit 5)
Frequency of CD4-bs-specific B cells
as measured by flow cytometry
Measured: at week 15 (visit 4, prior to vaccination 2) and week 27 (visit 6, prior to vaccination 3).
Response rate of Env-specific serum IgG binding antibodies
Measured: at approximately week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Magnitude of Env-specific serum IgG binding antibodies
Measured: at approximately week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Epitope specificity of Env-specific serum IgG binding antibodies
Measured: at approximately week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Breadth of Env-specific serum IgG binding antibodies
Measured: at approximately week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Response rate of neutralizing antibodies
as measured by TZM-bl assay
Measured: at approximately week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Potency of neutralizing antibodies
as measured by TZM-bl assay
Measured: at approximately week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Breadth of neutralizing antibodies
as measured by TZM-bl assay
Measured: at approximately week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Frequency of CD4-bs-specific B cells
as measured by flow cytometry
Measured: at week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Evolution of CD4-bs-specific BCRs
assessed by VH/VL sequencing of sorted B cells
Measured: at week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)]
Response rate of Env-specific serum IgG binding antibodies
Measured: at week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2025
- Study start17 Mar 2025
- Primary completion15 Jan 2027 (estimated)
- Study completion15 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 42 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06796686
- Sponsor's protocol ID
- HVTN 320
- Status last verified
- Sep 2025
- First submitted
- 22 Jan 2025
- Last updated
- 25 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of a Priming Regimen of 426c.Mod.Core-C4b Followed by HxB2.WT.Core-C4b Boosts, Both Adjuvanted With 3M-052 AF + Alum, in Adult Participants Without HIV and in Overall Good Health
- ClinicalTrials.gov ID
- NCT06796686
- Acronym / sponsor ID
- HVTN 320
- Conditions
- HIV
- Keywords
- HIV Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 17 Mar 2025 (actual)
- Primary completion
- 15 Jan 2027 (estimated)
- Study completion
- 15 Jan 2027 (estimated)
- First posted
- 28 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a partially randomized, open-label phase 1 study to evaluate the safety and immunogenicity of a priming regimen of 426c.Mod.Core-C4b adjuvanted with 3M-052 AF + Alum followed by boosts with HxB2.WT.Core-C4b adjuvanted with 3M-052 AF + Alum.
The primary hypothesis is that the boosting with HxB2.WT.Core-C4b adjuvanted with 3M-052 AF + Alum will further mature broadly neutralizing antibody (bnAb)-precursor B-cell lineages elicited by 426c.Mod.Core-C4b adjuvanted with 3M-052 AF + Alum.
426c.Mod.Core-C4b adjuvanted with 3M-052 AF + Alum has been tested in HVTN 301 previously, whereas the HxB2.WT.Core-C4b will be first-in-human (FIH).
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Active comparator | Biological: 426c.Mod.Core-C4b, Biological: HxB2.WT.Core-C4b, Biological: 3M-052-AF adjuvant, Other: Aluminum hydroxide suspension (Alum) adjuvant, Other: DiluentOne fractional dose of 426c.Mod.Core-C4b and two bolus doses of HxB2.WT.Core-C4b |
| Group 2A | Active comparator | Biological: 426c.Mod.Core-C4b, Biological: HxB2.WT.Core-C4b, Biological: 3M-052-AF adjuvant, Other: Aluminum hydroxide suspension (Alum) adjuvant, Other: DiluentOne fractional dose and one bolus dose of 426c.Mod.Core-C4b two bolus doses of HxB2.WT.Core-C4b |
| Group 2B | Active comparator | Biological: 426c.Mod.Core-C4b, Biological: HxB2.WT.Core-C4b, Biological: 3M-052-AF adjuvant, Other: Aluminum hydroxide suspension (Alum) adjuvant, Other: DiluentOne split dose and one bolus of 426c.Mod.Core-C4b and two bolus doses of HxB2.WT.Core-C4b |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (29 listed)
- Demonstrates an understanding of the study and is able and willing to complete the informed consent process.
- 18 to 55 years old, inclusive, on day of enrollment.
- Available for clinic follow-up through the last clinic visit, willing to undergo leukapheresis, and willing to be contacted after the last study-product administration, including for potential participation in additional studies.
- 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 320 PSRT are required prior to enrollment into HVTN 320.
- In good general health according to the clinical judgment of the site investigator.
Key exclusion criteria (32 listed)
- Volunteer who is breastfeeding/chestfeeding 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, provided that the HgbA1c is ≤ 8% within the last 6 months (sites may draw these at screening).
- Previous or current recipient of an investigational HIV vaccine (previous placebo/control recipients are not excluded).
- Receipt of non-HIV investigational 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 426c.Mod.Core-C4b426c.Mod.Core-C4b is supplied at a concentration of 2 mg/mL, 0.55 mL per vial. | Biological | Group 1, Group 2A, Group 2B |
| HxB2.WT.Core-C4bHxB2.WT.Core-C4b is supplied at a concentration of 1 mg/mL, 0.5 mL per vial | Biological | Group 1, Group 2A, Group 2B |
| 3M-052-AF adjuvantimmune response modifier (IRM) | Biological | Group 1, Group 2A, Group 2B |
| Aluminum hydroxide suspension (Alum) adjuvantAlhydrogel. | Other | Group 1, Group 2A, Group 2B |
| DiluentTris-NaCl buffer | Other | Group 1, Group 2A, Group 2B |
Primary outcome
Incidence of Local Signs and Symptoms within 14 Days Post-Vaccination
Time frame: Within 14 days of receiving study vaccine
Incidence of Systemic Reactogenicity Signs and Symptoms within 14 Days Post-Vaccination
Time frame: Within 14 days of receiving study vaccine
Incidence of Serious Adverse Events Over 52 Weeks Post-Vaccination
Time frame: throughout the study and for 52 weeks following any receipt of the study product
Incidence of Medically Attended Adverse Events Over 52 Weeks Post-Vaccination
Time frame: throughout the study and for 52 weeks following any receipt of the study product
Incidence of Adverse Events of Special Interest Over 52 Weeks Post-Vaccination
Time frame: throughout the study and for 52 weeks following any receipt of the study product
Incidence of Adverse Events Leading to Withdrawal or Discontinuation Over 52 Weeks Post-Vaccination
Time frame: throughout the study and for 52 weeks following any receipt of the study product
Frequency of CD4-bs-specific B cells before and approximately 12 weeks after each HxB2.WT.Core-C4b boost
Time frame: 12 weeks after each HxB2.WT.Core-C4b boost
assessed by flow cytometry
Evolution of CD4-bs-Specific BCRs Before and 12 Weeks After Each HxB2.WT.Core-C4b Boost
Time frame: 12 Weeks After Each HxB2.WT.Core-C4b Boost
Assessed by VH/VL Sequencing of Sorted B Cells
39 secondary outcomes
Response rate of serum antibodies at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost
Time frame: 2 weeks after each HxB2.WT.Core-C4b boost
Potency of serum antibodies at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost
Time frame: 2 weeks after each HxB2.WT.Core-C4b boost
Neutralizing breadth of serum antibodies at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost
Time frame: 2 weeks after each HxB2.WT.Core-C4b boost
Response rate of Env-specific serum IgG binding antibodies will be assessed at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost
Time frame: 2 weeks after each HxB2.WT.Core-C4b boost
Magnitude of Env-specific serum IgG binding antibodies will be assessed at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost
Time frame: 2 weeks after each HxB2.WT.Core-C4b boost
Epitope specificity of Env-specific serum IgG binding antibodies will be assessed at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost
Time frame: 2 weeks after each HxB2.WT.Core-C4b boost
Breadth of Env-specific serum IgG binding antibodies will be assessed at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost
Time frame: 2 weeks after each HxB2.WT.Core-C4b boost
Magnitude of binding of Env-specific IgG binding antibodies
Time frame: 2 weeks after each HxB2.WT.Core-C4b boost
Epitope specificity of Env-specific IgG binding antibodies
Time frame: 2 weeks after each HxB2.WT.Core-C4b boost
Breadth of Env-specific IgG binding antibodies
Time frame: 2 weeks after each HxB2.WT.Core-C4b boost
Potency of neutralizing antibodies
Time frame: 2 weeks after each HxB2.WT.Core-C4b boost
Breadth of neutralizing antibodies
Time frame: 2 weeks after each HxB2.WT.Core-C4b boost
Response rate of Env-specific serum IgG binding antibodies
Time frame: at week 6 (visit 3) and week 17 (visit 5)
Magnitude of Env-specific serum IgG binding antibodies
Time frame: at week 6 (visit 3) and week 17 (visit 5)
Epitope specificity of Env-specific serum IgG binding antibodies
Time frame: at week 6 (visit 3) and week 17 (visit 5)
Breadth of Env-specific serum IgG binding antibodies
Time frame: at week 6 (visit 3) and week 17 (visit 5)
Response rate of neutralizing antibodies
Time frame: at week 6 (visit 3) and week 17 (visit 5)
Potency of neutralizing antibodies
Time frame: at week 6 (visit 3) and week 17 (visit 5)
Breadth of neutralizing antibodies
Time frame: at week 6 (visit 3) and week 17 (visit 5)
Frequency of CD4-bs-specific B cells
Time frame: at week 15 (visit 4, prior to vaccination 2) and week 27 (visit 6, prior to vaccination 3)
Evolution of CD4-bs-specific BCRs
Time frame: at week 15 (visit 4, prior to vaccination 2)
Response rate of Env-specific serum IgG binding antibodies
Time frame: at approximately 4 weeks post the first prime (visit 3) and week 17 (visit 5)
Magnitude of Env-specific serum IgG binding antibodies
Time frame: at approximately 4 weeks post the first prime (visit 3) and week 17 (visit 5)
Epitope specificity of Env-specific serum IgG binding antibodies
Time frame: at approximately 4 weeks post the first prime (visit 3) and week 17 (visit 5)
Breadth of Env-specific serum IgG binding antibodies
Time frame: at approximately 4 weeks post the first prime (visit 3) and week 17 (visit 5)
Response rate of neutralizing antibodies
Time frame: at approximately 4 weeks post the first prime (visit 3) week 17 (visit 5)
Potency of neutralizing antibodies
Time frame: at approximately 4 weeks post the first prime (visit 3) week 17 (visit 5)
Breadth of neutralizing antibodies
Time frame: at approximately 4 weeks post the first prime (visit 3) week 17 (visit 5)
Frequency of CD4-bs-specific B cells
Time frame: at week 15 (visit 4, prior to vaccination 2) and week 27 (visit 6, prior to vaccination 3).
Response rate of Env-specific serum IgG binding antibodies
Time frame: at approximately week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Magnitude of Env-specific serum IgG binding antibodies
Time frame: at approximately week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Epitope specificity of Env-specific serum IgG binding antibodies
Time frame: at approximately week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Breadth of Env-specific serum IgG binding antibodies
Time frame: at approximately week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Response rate of neutralizing antibodies
Time frame: at approximately week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Potency of neutralizing antibodies
Time frame: at approximately week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Breadth of neutralizing antibodies
Time frame: at approximately week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Frequency of CD4-bs-specific B cells
Time frame: at week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Evolution of CD4-bs-specific BCRs
Time frame: at week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)]
Response rate of Env-specific serum IgG binding antibodies
Time frame: at week 29 (visit 7), week 39 (visit 8, prior to vaccination 4), week 41 (visit 9), and week 51 (visit 10)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Bridge HIV, San Francisco Department of Public Health
San Francisco, United States
The Hope Clinic of the Emory Vaccine Research Center; Emory University
Decatur, United States
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 426c.Mod.Core-C4b, HxB2.WT.Core-C4b and 3M-052-AF adjuvant in people with HIV, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 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 29 inclusion and 32 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: looking for participants now, as of the sponsor's last update on 25 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Local Signs and Symptoms within 14 Days Post-Vaccination (time frame: Within 14 days of receiving study vaccine). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Sep 2025.