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Updated June 2026 · ClinicalTrials.gov

RECRUITINGPhase 1INTERVENTIONAL

Safety and Immunogenicity Study of Three mRNAs Encoding HIV Immunogens in Adult Participants Without HIV and in Overall Good Health in South Africa.

A Phase 1, Placebo-controlled, Blinded, Dose-escalation Study to Evaluate the Safety and Immunogenicity of mRNAs Encoding HIV Immunogens (eOD-GT8 60mer, Core-g28v2 60mer, N332-GT5 gp151) in Adult Participants Without HIV and in Overall Good Health in South Africa.

Safety and Immunogenicity Study of Three mRNAs Encoding HIV Immunogens in Adult Participants Without HIV and in Overall Good Health in South Africa. (NCT06694753) is a Phase 1 interventional studying HIV Infections, sponsored by International AIDS Vaccine Initiative. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

The purpose of this study is to evaluate the safety and immunogenicity of mRNAs encoding HIV immunogens (eOD-GT8 60mer, core-g28v2 60mer, N332-GT5 gp151) in adult participants without HIV and in overall good health in South Africa.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For HIV Infections, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 96 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused HIV Infections subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Demonstrates an understanding of the study and is able and willing to complete the willing to sign a consent form process. 2. 18 to ≤ 55 years old, on day of enrollment. 3. Available for clinic follow-up through the last clinic visit. 4. Willingness to undergo FNA and leukapheresis. 5. 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 IAVI Medical Monitor are required prior to enrollment into DESIIGN001/IAVI G004. 6. In good general health according to the clinical judgment of the Investigator. 7. Physical examination and laboratory results without clinically significant findings that would interfere with assessment of safety or reactogenicity in the clinical judgment of the Investigator. 8. Assessed by clinical staff as having a low likelihood of acquiring HIV per guidelines (see Appendix 4), agrees to discuss their potential for HIV acquisition, agrees to prevention counseling, and agrees to avoid behaviors associated with a higher likelihood of acquiring HIV through the final study visit. "Low likelihood" may include persons stably taking pre-exposure prophylaxis (PrEP) as prescribed in Appendix 4. 9. Hemoglobin (Hgb): - ≥12.0 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. 10. White blood cell (WBC) count = 2,500 to 12,000/mm3. 11. Platelets = 125,000 to 550,000/mm3. 12. Alanine aminotransferase (ALT) \<2.5 × upper limit of institutional reference range. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: 1. Demonstrates an understanding of the study and is able and willing to complete the informed consent process. 2. 18 to ≤ 55 years old, on day of enrollment. 3. Available for clinic follow-up through the last clinic visit. 4. Willingness to undergo FNA and leukapheresis. 5. 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 IAVI Medical Monitor are required prior to enrollment into DESIIGN001/IAVI G004. 6. In good general health according to the clinical judgment of the Investigator. 7. Physical examination and laboratory results without clinically significant findings that would interfere with assessment of safety or reactogenicity in the clinical judgment of the Investigator. 8. Assessed by clinical staff as having a low likelihood of acquiring HIV per guidelines (see Appendix 4), agrees to discuss their potential for HIV acquisition, agrees to prevention counseling, and agrees to avoid behaviors associated with a higher likelihood of acquiring HIV through the final study visit. "Low likelihood" may include persons stably taking pre-exposure prophylaxis (PrEP) as prescribed in Appendix 4. 9. Hemoglobin (Hgb): * ≥12.0 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. 10. White blood cell (WBC) count = 2,500 to 12,000/mm3. 11. Platelets = 125,000 to 550,000/mm3. 12. Alanine aminotransferase (ALT) \<2.5 × upper limit of institutional reference range. 13. Serum creatinine ≤1.1× upper limit of normal (ULN) based on the institutional normal range. 14. Systolic blood pressure of 90 to \<140 mmHg and diastolic blood pressure of 50 to \<90 mmHg at the 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 mmHg systolic or 100 mmHg diastolic during the current study evaluation is exclusionary. 15. Negative HIV test results by one of the following options: * A negative European Conformity (CE)-marked enzyme immunoassay (EIA) * A chemiluminescent microparticle immunoassay (CMIA) * A negative result on 2 HIV rapid tests (one of these rapid tests must be CE-marked) 16. Negative for anti-Hepatitis C virus (HCV) Abs (anti-HCV) or negative HCV nucleic acid test (NAT) if anti-HCV Abs are detected. 17. Negative for Hepatitis B surface antigen (HBsAg). 18. For volunteers AFAB or assigned intersex at birth 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 time point (see Appendix 5). * 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 or menopause (no menses for ≥1 year) are not required to undergo pregnancy testing. 19. Volunteers AFAB or assigned 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 time point. Exclusion Criteria: 1. Volunteer is nursing or pregnant. 2. Body mass index (BMI) ≥40 kg/m2. Enrollment of individuals with BMI ≥40 kg/m2, whom the site investigator assesses are in good health, may be considered by the IAVI Medical Monitor. 3. Diabetes mellitus (DM). Type 2 DM controlled with diet alone (and confirmed by HgbA1c ≤7% 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 IAVI Medical Monitor on a case-by-case basis, provided that the HgbA1c is ≤8% within the last 6 months (CRC staff may draw these at screening). 4. Previous or current recipient of an investigational HIV vaccine (previous placebo/control recipients are not excluded). 5. 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 authorizing this clinical trial. 6. Congenital or acquired immunodeficiency, including systemic medication use likely to impair immune response to vaccine in the opinion of the Investigator, such as glucocorticoid use, prednisone ≥10 mg/day within 3 months prior to enrollment. 7. Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires approval by the IAVI Medical Monitor. 8. Previous receipt of VRC01 or VRC07-523LS monoclonal antibody (mAb). 9. Receipt of any vaccine within 4 weeks prior to enrollment or planned receipt within 4 weeks of investigational vaccine administration. 10. History of myocarditis and/or pericarditis. 11. A past history of immune-mediated disease, including but not limited to thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, celiac disease, seronegative inflammatory arthritis, systemic sclerosis, and Type 1 diabetes (for other examples, see Appendix 8). 12. History of or active severe skin conditions, including, but not limited to, cutaneous mastocytosis, psoriasis, atopic dermatitis, lichen planus, hidradenitis suppurativa, bullous pemphigoid, and urticarial vasculitis. 13. Systemic or local conditions with urticaria as a manifestation, including urticarial vasculitis, maculo-papular cutaneous mastocytosis (formerly urticaria pigmentosa), mast cell activation syndrome, Gleich's syndrome (episodic angioedema with eosinophilia), Well's syndrome (granulomatous dermatitis with eosinophilia/eosinophilic cellulitis), bullous pemphigoid, or adult-onset Still's disease. 14. Receipt of antigen-based immunotherapy. 15. 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, approval by the IAVI Medical Monitor is required for enrollment. 16. History of serious reaction (eg, hypersensitivity, anaphylaxis) to any vaccine or component of the study-vaccine regimen. 17. History of hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema. 18. History of urticaria and/or dermatographism. 19. History of atopy (diagnosed or confirmed by a clinician). 20. Bleeding disorder diagnosed by a clinician that would make study procedures a contraindication. 21. History of seizure(s) within the past 3 years, or if volunteer has used medications to prevent or treat seizure(s) at any time within the past 3 years. 22. Asplenia or functional asplenia. 23. 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, any suicide attempt within the past 1 year (if between 1 and 2 years, consult the IAVI Medical Monitor for approval), or cancer that, in the clinical judgment of the Investigator, has potential for recurrence (excluding basal cell carcinoma). 24. Asthma (diagnosed or confirmed by a clinician). 25. History of allergy to local anesthetic (Novocaine, Lidocaine). 26. 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. 27. Has donated ≥450 mL of blood products within 28 days prior to the Screening Visit or plans to donate blood products within 28 days post study injection. 28. Is working or has worked as study personnel or is an immediate family member or house member of study personnel, study site staff, or Sponsor personnel.

Treatments Being Tested

BIOLOGICAL

mRNA-1645-eODGT8

eOD-GT8 60mer is a self-assembling nanoparticle composed of 60 subunits of the engineered HIV-1 gp120 outer domain germline targeting version 8 (eOD-GT8) fused to an engineered form of a bacterial enzyme, Lumazine Synthase, through a 15-amino acid Glycine-Serine linker. eOD-GT8 60mer will be delivered using an mRNA lipid nanoparticle (LNP) platform. To be administered by intramuscular (IM) injection at doses of 10 or 30 mcg.

BIOLOGICAL

mRNA-1645-CoreG28v2

core-g28v2 60mer is a nanoparticle composed of 60 protein subunits of an engineered core-gp120 fused to an engineered form of a bacterial enzyme, Lumazine Synthase, through a 21-amino acid Glycine-Serine linker. Core-g28v2 60mer will be delivered using an mRNA-LNP platform. To be administered by IM injection at doses of 10 or 30 mcg.

BIOLOGICAL

mRNA-1645-N332GT5

N332-GT5 gp151 is an HIV envelope glycoprotein gp151 trimer based on BG505 SOSIP MD39 (clade A) trimer with "germline-targeting" mutations added that confer the ability to bind germline precursors of BG18 class B cells. N332-GT5 gp151 will be delivered using an mRNA-LNP platform. To be administered by IM injection at doses of 10 or 30 mcg.

BIOLOGICAL

Placebo

Saline

Locations (6)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Setshaba Research Centre CRS
Soshanguve, Gauteng, South Africa
Perinatal HIV Research Unit (PHRU)
Soweto, Gauteng, South Africa
CAPRISA eThekwini CRS
Durban, KwaZulu-Natal, South Africa
Isipingo CRS
Isipingo, KwaZulu-Natal, South Africa
Desmond Tutu Health Foundation Emavundleni CRS
Cape Town, Western Cape, South Africa
Desmond Tutu Health Foundation- Groote Schuur Hospital/J52
Cape Town, Western Cape, South Africa

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06694753), the sponsor (International AIDS Vaccine Initiative), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06694753 clinical trial studying?

The purpose of this study is to evaluate the safety and immunogenicity of mRNAs encoding HIV immunogens (eOD-GT8 60mer, core-g28v2 60mer, N332-GT5 gp151) in adult participants without HIV and in overall good health in South Africa. The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06694753?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06694753?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06694753. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06694753. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-07 · Data from ClinicalTrials.gov.