A Clinical Trial to Evaluate the Safety and Immunogenicity of BG505 MD39.3, BG505 MD39.3 gp151, and BG505 MD39.3 gp151 CD4KO HIV Trimer mRNA Vaccines in Healthy, HIV-uninfected Adult Participants
A Phase 1, Randomized, Open-label Clinical Trial to Evaluate the Safety and Immunogenicity of BG505 MD39.3, BG505 MD39.3 gp151, and BG505 MD39.3 gp151 CD4KO HIV Trimer mRNA Vaccines in Healthy, HIV-uninfected Adult Participants
2 other identifiers
interventional
108
1 country
10
Brief Summary
This is an open-label, multicenter, randomized phase 1 study to evaluate the safety and immunogenicity of BG505 MD39.3, BG505 MD39.3 gp151, and BG505 MD39.3 gp151 CD4KO HIV trimer mRNA. These trimers are based on the BG505 MD39 native-like trimer reported in Steichen et al. Immunity 2016. The primary hypothesis is that the BG505 MD39.3 soluble and membrane-bound trimer mRNA vaccines will be safe and well-tolerated among HIV-uninfected individuals and will elicit autologous neutralizing antibodies.
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 Feb 2022
Longer than P75 for phase_1 hiv-infections
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 30, 2021
CompletedFirst Posted
Study publicly available on registry
February 1, 2022
CompletedStudy Start
First participant enrolled
February 11, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 17, 2023
CompletedResults Posted
Study results publicly available
October 31, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
June 24, 2027
ExpectedOctober 14, 2025
September 1, 2025
1.4 years
December 30, 2021
July 18, 2024
September 25, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (18)
Number of Participants Reporting Local Solicited Adverse Events Signs and Symptoms: Pain and/or Tenderness
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, July 2017. The maximum grade observed for each symptom over the time frame is presented.
Measured through 7 days after each vaccine dose
Number of Participants Reporting Local Unsolicited Adverse Events Signs and Symptoms: Erythema and/or Induration
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, July 2017. The maximum grade observed for each symptom over the time frame is presented.
Measured through 7 days after each vaccine dose
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, July 2017. The maximum grade observed for each symptom over the time frame is presented.
Measured through 7 days after each vaccine dose
Chemistry and Hematology Laboratory Measures - ALT in U/L
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population
Measured during Screening, Days 8, 64, 176 and 225
Chemistry and Hematology Laboratory Measures - Creatinine in mg/dL
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population
Measured during Screening, Days 8, 64, 176 and 225
Chemistry and Hematology Laboratory Measures - Hemoglobin in g/dL
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population
Measured during Screening, Days 8, 64, 176 and 225
Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil, Basophils, Eosinophils Count in 1000 Cells/Cubic mm
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population
Measured during Screening, Days 8, 64, 176 and 225
Chemistry and Hematology Laboratory Measures - Platelets, WBC in 1000 Cells/Cubic mm
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population
Measured during Screening, Days 8, 64, 176 and 225
Number of Lab Grade > 1 for ALT, Creatinine, Hemoglobin, Lymphocyte Count, Neutrophil Count, Platelets, White Blood Cells (WBC), Basophils, Eosinophils
The number (percentage) of participants with lab grade \> 1 for alanine aminotransferase (ALT), creatinine, hemoglobin, lymphocyte count, neutrophil count, platelets, white blood cells (WBC), basophils, eosinophils was summarized by arm
Measured during Screening, Days 8, 64, 176 and 225
Number of Participants Reporting Adverse Events (AEs), by Severity Grade
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply)
30 days following each injection
Number of Participants Reporting Adverse Events (AEs), by Relationship to Study Product
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply).
30 days following each injection
Number of Participants Reporting Serious Adverse Events (SAEs)
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply)
Measured through Month 12
Number of Participants Reporting Medically Attended Adverse Events (MAAEs)
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply)
Measured through Month 12
Number of Participants Reporting Adverse Events of Special Interest (AESIs)
There were no adverse events of special interest reported by any participant.
Measured through Month 12.
Number of Participants With Study Product Discontinuation Associated With an AE or Reactogenicity
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply)
Measured through Month 12
Number of Participants With Early Study Termination Associated With an AE or Reactogenicity
There were no early study terminations associated with an AE or reactogenicity reported by any participant.
Measured through Month 12.
Magnitude of Serum Antibody Neutralization of a Vaccine-matched Tier 2 HIV-1 Strain
Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. The assay performed in TZM-bl cells measured neutralization titers against a panel of autologous Env-pseudotyped viruses that exhibit tier 2 neutralization phenotype: BG505/T332N.
2 weeks after the 3rd vaccination timepoint (M6.5)
Response Rate of Serum Antibody Neutralization of a Vaccine-matched Tier 2 HIV-1 Strain
Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. The assay performed in TZM-bl cells measured neutralization titers against a panel of autologous Env-pseudotyped viruses that exhibit tier 2 neutralization phenotype: BG505/T332N.
2 weeks after the 3rd vaccination timepoint (M6.5)
Secondary Outcomes (6)
Magnitude of Serum Antibody Neutralization of a Vaccine-matched Tier 2 HIV-1 Strain
2 weeks after the 2nd vaccination (M2.5), 6 months after the 3rd vaccination (M12)
Response Rate of Serum Antibody Neutralization of a Vaccine-matched Tier 2 HIV-1 Strain
2 weeks after the 2nd vaccination (M2.5), 6 months after the 3rd vaccination (M12)
Magnitude of Serum IgG Binding Antibodies to the BG505 Trimer, and Specific Epitopes (Base of Trimer, V3, Internal Epitope) as Measured by Binding Antibody Multiplex Assay (BAMA)
2 weeks after the 2nd vaccination (M2.5), 2 weeks after the 3rd vaccination (M6.5), 6 months after the 3rd vaccination (M12)
Response Rate Serum IgG Binding Antibodies to the BG505 Trimer, and Specific Epitopes (Base of Trimer, V3, Internal Epitope) as Measured by Binding Antibody Multiplex Assay (BAMA)
2 weeks after the 2nd vaccination (M2.5), 2 weeks after the 3rd vaccination (M6.5), 6 months after the 3rd vaccination (M12)
Magnitude of CD4+ T-cell Responses as Assessed by Intracellular Cytokine Staining Assays (ICS)
2 weeks after the 3rd vaccination (M6.5)
- +1 more secondary outcomes
Study Arms (6)
Part A, Group 1: Low dose BG505 MD39.3 mRNA
EXPERIMENTAL18 participants Dose: 100mcg of BG505 MD39.3 mRNA formulated administered at months 0, 2, and 6
Part A, Group 2: Low dose BG505 MD39.3 gp151 mRNA
EXPERIMENTAL18 participants Dose: 100mcg of BG505 MD39.3 gp151 mRNA administered at months 0, 2, and 6
Part A, Group 3: Low dose BG505 MD39.3 gp151 CD4KO mRNA
EXPERIMENTAL18 participants Dose: 100mcg of BG505 MD39.3 gp151 CD4KO mRNA administered at months 0, 2, and 6
Part B, Group 1: BG505 MD39.3 mRNA
EXPERIMENTAL18 participants Dose: 250mcg of BG505 MD39.3 mRNA administered at months 0, 2, and 6
Part B, Group 2: BG505 MD39.3 gp151 mRNA
EXPERIMENTAL18 participants Dose: 250mcg of BG505 MD39.3 gp151 mRNA administered at months 0, 2, and 6
Part B, Group 3: BG505 MD39.3 gp151 CD4KO mRNA
EXPERIMENTAL18 participants Dose: 250mcg of BG505 MD39.3 gp151 CD4KO mRNA administered at months 0, 2, and 6
Interventions
Administered by IM injection
Administered by IM injection
Administered by IM injection
Eligibility Criteria
You may qualify if:
- Able and willing to complete the informed consent process, including an Assessment of Understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly.
- years old, inclusive, on day of enrollment.
- Agrees to comply with planned study procedures and be available for clinic follow-up through the last clinic visit.
- Agrees not to enroll in another study of an investigational agent during participation in the trial.
- In good general health according to the clinical judgement 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.
- Assessed as low risk for HIV acquisition per low risk guidelines, agrees to discuss HIV infection risks, agrees to risk reduction counseling, and agrees to avoid behavior associated with high risk of HIV exposure through the final study visit. Low risk may include persons stably taking pre-exposure prophylaxis (PrEP) as prescribed for 6 months or longer.
- Hemoglobin
- Greater than or equal to 11.0 g/dL for volunteers who were assigned female sex at birth
- Greater than or equal to 13.0 g/dL for volunteers who were assigned male sex at birth and transgender males who have been on hormone therapy for more than 6 consecutive months
- Greater than or equal to 12.0 g/dL for transgender females who have been on hormone therapy for more than 6 consecutive months
- For transgender participants who have been on hormone therapy for less than 6 consecutive months, determine hemoglobin eligibility based on the sex assigned at birth
- White blood cell (WBC) count \> 3,500/mm3
- Platelets ≥125,000 /mm3
- Alanine aminotransferase (ALT) \< 2.5 x upper limit of normal (ULN) based on the institutional normal range
- +7 more criteria
You may not qualify if:
- Volunteer who is breast-feeding or pregnant.
- Hypertension that is not well controlled. If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined in this protocol as consistently \< 140 mm Hg systolic and \< 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤ 150 mm Hg systolic and ≤ 100 mm Hg diastolic. For these volunteers, blood pressure must be \< 140 mm Hg systolic and \< 90 mm Hg diastolic at enrollment. If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg at enrollment.
- Previous or current recipient of an investigational HIV vaccine (previous placebo recipients are not excluded).
- Acutely ill or febrile (temperature ≥ 38.0°C/100.4°F) on the day of the first vaccination. Participants meeting this criterion may be rescheduled within the enrollment window period. Afebrile participants with minor illnesses can be enrolled at the discretion of the Investigator.
- Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires PSRT approval.
- Receipt of any of the following:
- Within 4 weeks prior to enrollment:
- Any licensed live, attenuated vaccine
- Any emergency use authorized (EUA) or licensed mRNA-based SARS-CoV-2 vaccine
- Within 2 weeks prior to enrollment:
- Any licensed killed/subunit/inactivated vaccine
- Any EUA or licensed adenoviral-vectored or protein SARS-CoV-2 vaccines Receipt of any SARS-CoV-2 vaccination series should be completed 4 weeks prior to enrollment when possible; however, exceptions may be made by approval of the HVTN 302 PSRT.
- 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 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 any component of the study vaccine.
- History of myocarditis and/or pericarditis.
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
Alabama CRS [31788]
Birmingham, Alabama, 35222, United States
UCLA Vine Street Clinic CRS [31607]
Los Angeles, California, 90038, United States
Bidmc Vcrs [32077]
Boston, Massachusetts, 02115, United States
Brigham and Women's Hospital Vaccine CRS [30007]
Boston, Massachusetts, 02115, United States
New York Blood Center CRS [31801]
New York, New York, 10065, United States
Columbia P&S CRS [30329]
New York, New York, 30329, United States
University of Rochester Vaccines to Prevent HIV Infection CRS [31467]
Rochester, New York, 14642, United States
Penn Prevention CRS [30310]
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh CRS [1001]
Pittsburgh, Pennsylvania, 15213, United States
Seattle Vaccine and Prevention CRS [30331]
Seattle, Washington, 98104, United States
Related Publications (1)
Riddler SA, Moodie Z, Clark J, Yen C, Allen M, Furch BD, Lu H, Grant S, Mondal K, Anderson M, Maenza J, Lemos MP, Woodward Davis AS, Walsh SR, Sobieszczyk ME, Frank I, Goepfert P, Stephenson KE, Baden LR, Tieu HV, Keefer MC, McElrath MJ, Kublin JG, Corey L. High Frequency of Chronic Urticaria Following an Investigational HIV-1 BG505 MD39.3 Trimer mRNA Vaccine in a Phase 1, Randomized, Open-Label Clinical Trial (HVTN 302). Ann Intern Med. 2025 Jul;178(7):963-974. doi: 10.7326/ANNALS-24-02701. Epub 2025 Apr 29.
PMID: 40294415DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Jessica Andriesen, PhD, Associate Director of HVTN SDMC Operations
- Organization
- Fred Hutchinson Cancer Center
Study Officials
- STUDY CHAIR
Jesse Clark, MD
University of California, Los Angeles
- STUDY CHAIR
Sharon Riddler, MD
University of Pittsburgh
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- PREVENTION
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 30, 2021
First Posted
February 1, 2022
Study Start
February 11, 2022
Primary Completion
July 17, 2023
Study Completion (Estimated)
June 24, 2027
Last Updated
October 14, 2025
Results First Posted
October 31, 2024
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will not share