Safety and Immunogenicity Study of Three mRNAs Encoding HIV Immunogens in Adult Participants Without HIV and in Overall Good Health in South Africa.
IAVI G004
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.
1 other identifier
interventional
96
1 country
6
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 hiv-infections
Started Dec 2025
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 5, 2024
CompletedFirst Posted
Study publicly available on registry
November 19, 2024
CompletedStudy Start
First participant enrolled
December 15, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 8, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 31, 2027
May 7, 2026
May 1, 2026
12 months
November 5, 2024
May 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
To assess the incidence of local and systemic reactogenecity and treatment-emergent adverse events [Safety and Tolerability].
* Local and systemic reactogenicity signs and symptoms will be collected for a minimum of 7 days following receipt of any study vaccination. * AEs leading to early participant withdrawal or permanent discontinuation, SAEs, medically attended adverse events (MAAEs), and AESIs will be collected throughout the study. Additionally, all AEs will be collected for 30 days after any receipt of study vaccination.
Measured a minimum of 7 days following receipt of any study vaccination
To evaluate the induction of VRC01- or BG18-class IgG B cell responses by the vaccine regimens.
• Proportion of vaccinees with VRC01- or BG18-class IgG B cells, and frequency of VRC01- or BG18-class B cells among IgG+ B cells in PBMCs or in germinal centers, at baseline and after each study product administration, as determined by B-cell phenotyping and BCR sequencing.
V01 [W0, baseline] V04 [W7.5, 7.5 wks. post 1st vacc.] V06 [W10, 2 wks. post 2nd vacc.] V07 [W15.5, 7.5 wks. post 2nd vacc.]
Secondary Outcomes (1)
To evaluate vaccine-specific and epitope-specific binding Ab responses elicited by the vaccine regimens.
Measured at baseline (at Week 0), 2 weeks post 1st vaccination (at Week 2), 7.5 weeks post 1st vaccination (at Week 7.5), 2 weeks post 2nd vaccination (at Week 10), and 7.5 weeks post 2nd vaccination (at Week 15.5)
Study Arms (8)
Cohort 1A Group 1: mRNA-1645-eODGT8 + mRNA-1645-CoreG28v2
EXPERIMENTALParticipants will receive one injection of 10 mcg mRNA-1645-eODGT8 to be administered as a 0.5 mL IM injection into the deltoid at Week 0 and one injection of 10 mcg mRNA-1645-CoreG28v2 to be administered as a 0.5 mL IM injection into the deltoid at Week 8.
Cohort 1A Group 2: Placebo
PLACEBO COMPARATORParticipants will receive 0.9% sodium chloride to be administered as a 0.5-mL IM injection into the deltoid at Weeks 0 and 8.
Cohort 2A Group 3: mRNA-1645-N332GT5
EXPERIMENTALParticipants will receive 10 mcg of mRNA-1645-N332GT5 to be administered as a 0.5 mL IM injection into the deltoid at Weeks 0 and 8.
Cohort 2A Group 4: Placebo
PLACEBO COMPARATORParticipants will receive 0.9% sodium chloride to be administered as a 0.5-mL IM injection into the deltoid at Week 0 and Week 8.
Cohort 1B Group 5: mRNA-1645-eODGT8 + mRNA-1645-CoreG28v2
EXPERIMENTALParticipants will receive one injection of 30 mcg mRNA-1645-eODGT8 to be administered as a 0.5 mL IM injection into the deltoid at Week 0 and one injection of 30 mcg mRNA-1645-CoreG28v2 to be administered as a 0.5 mL IM injection into the deltoid at Week 8.
Cohort 1B Group 6: Placebo
PLACEBO COMPARATORParticipants will receive 0.9% sodium chloride to be administered as a 0.5-mL IM injection into the deltoid at Week 0 and Week 8.
Cohort 2B Group 7: mRNA-1645-N332GT5
EXPERIMENTALParticipants will receive 30 mcg of mRNA-1645-N332GT5 to be administered as a 0.5 mL IM injection into the deltoid at Weeks 0 and 8.
Cohort 2B Group 8: Placebo
PLACEBO COMPARATORParticipants will receive 0.9% sodium chloride to be administered as a 0.5-mL IM injection into the deltoid at Week 0 and Week 8.
Interventions
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.
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.
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.
Saline
Eligibility Criteria
You may qualify if:
- Demonstrates an understanding of the study and is able and willing to complete the informed consent process.
- to ≤ 55 years old, on day of enrollment.
- Available for clinic follow-up through the last clinic visit.
- Willingness to undergo FNA and leukapheresis.
- 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.
- In good general health according to the clinical judgment of the 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 Investigator.
- 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.
- 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.
- White blood cell (WBC) count = 2,500 to 12,000/mm3.
- Platelets = 125,000 to 550,000/mm3.
- +13 more criteria
You may not qualify if:
- Volunteer is nursing or pregnant.
- 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.
- 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 authorizing this clinical trial.
- 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.
- 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.
- Previous receipt of VRC01 or VRC07-523LS monoclonal antibody (mAb).
- Receipt of any vaccine within 4 weeks prior to enrollment or planned receipt within 4 weeks of investigational vaccine administration.
- History of myocarditis and/or pericarditis.
- 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).
- 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.
- 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.
- Receipt of antigen-based immunotherapy.
- 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.
- History of serious reaction (eg, hypersensitivity, anaphylaxis) to any vaccine or component of the study-vaccine regimen.
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- The Scripps Research Institutecollaborator
- International AIDS Vaccine Initiativelead
- ModernaTX, Inc.collaborator
- National Institute of Allergy and Infectious Diseases (NIAID)/Division of AIDS (DAIDS)collaborator
- Bill and Melinda Gates Foundationcollaborator
Study Sites (6)
Setshaba Research Centre CRS
Soshanguve, Gauteng, 0152, South Africa
Perinatal HIV Research Unit (PHRU)
Soweto, Gauteng, 1862, South Africa
CAPRISA eThekwini CRS
Durban, KwaZulu-Natal, 4001, South Africa
Isipingo CRS
Isipingo, KwaZulu-Natal, 4110, South Africa
Desmond Tutu Health Foundation Emavundleni CRS
Cape Town, Western Cape, 7750, South Africa
Desmond Tutu Health Foundation- Groote Schuur Hospital/J52
Cape Town, Western Cape, 7925, South Africa
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Linda-Gail Bekker
Desmond Tutu Health Foundation/Center, University of Cape Town
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- The study team will be blinded to treatment assignment within a cohort but not across cohorts
- Purpose
- PREVENTION
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 5, 2024
First Posted
November 19, 2024
Study Start
December 15, 2025
Primary Completion (Estimated)
December 8, 2026
Study Completion (Estimated)
March 31, 2027
Last Updated
May 7, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- No later than 12 months after the trial completion.
- Access Criteria
- The study data and documents will be shared publicly after the conclusion of the study and at the time of primary manuscript publication. Documentation will include; Study protocols, annotated CRFs and Statistical Analysis Plans. The datasets will be posted as SAS transport files XPT and as CSV files. IAVI will post packages to the Vivli online repository, accessible to the public by website. Vivli uses an independent peer review process to evaluate the validity of external requests.To protect participant privacy and comply with data protection laws, IAVI will utilize an independent organization who specializes in clinical trial data anonymization and privacy to prepare anonymized data packages for public consumption. Manuscripts will be made available at the time of publication through placement in apublicly available repository and openly licensed. Post-publication Data Packages wil be made available at publication in compliance with specific journal requirements.
A primary manuscript will be prepared after the data analysis is available and the results of the study will be published in searchable, peer reviewed scientific literature according to the, allowing unrestricted access and reuse of all peer-reviewed published research.Underlying, anonymized datasets will be made publicly available. The final clinical study report will be made available to the principal investigators. The Sponsor will also provide investigators with the full summary of the study results, which the investigators may share with the study participants and stakeholders, as appropriate.