Trial to Evaluate the Safety and Immunogenicity of Priming Regimens of 426c.Mod.Core-C4b and Optional Boost Regimen With HIV Trimer BG505 SOSIP.GT1.1 gp140, Both Adjuvanted With 3M-052-AF + Alum in Healthy, Adult Participants Without HIV
A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Priming Regimens of 426c.Mod.Core-C4b and Optional Boost Regimen With HIV Trimer BG505 SOSIP.GT1.1 gp140, Both Adjuvanted With 3M-052-AF + Alum in Healthy, Adult Participants Without HIV
1 other identifier
interventional
52
1 country
6
Brief Summary
The clinical study is designed to evaluate the ability of two priming vaccine regimens to activate and induce the maturation of cross-reactive CD4 binding site (CD4-bs) antibodies, including VRC01-class antibodies. VRC01- class antibodies are highly desirable to elicit via vaccination because they have broad cover all clades of HIV and passive administration of VRC01 monoclonal antibodies has been demonstrated to prevent acquisition of susceptible HIV strains in clinical trials. The study will assess whether B cells expressing VRC01-like B cell receptors proliferate following immunization with a 'germline-targeting' recombinant Env immunogen. The study will also test whether an immunization strategy based upon fractionated dose delivery of the immunogen may improve the maturation of VRC01-class B cells when compared to traditional bolus dosing. In addition, the study will test whether alterations in the dose of the subsequent boost immunizations affects VRC01-class B cell activation and the rate of antibody affinity maturation. The primary hypothesis of the optional boost regimen is that BG505 SOSIP.GT1.1 gp140 adjuvated with 3M-052-AF + Alum is safe and well-tolerated and will further mature B-cell lineages elicited by 426c.Mod.Core-C4b priming regimens.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Aug 2022
Typical duration for phase_1
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
July 15, 2022
CompletedFirst Posted
Study publicly available on registry
July 22, 2022
CompletedStudy Start
First participant enrolled
August 22, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 23, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
May 21, 2026
ExpectedApril 13, 2026
April 1, 2026
3.3 years
July 15, 2022
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (8)
Number of participants showing local vaccination reactogenicity signs and symptoms
Assessed by clinic staff. For a given sign or symptom, each subject's reactogenicity will be counted once under the maximum severity for each injection/ vaccination.
14 days following each vaccination
Number of participants showing systemic vaccination reactogenicity signs and symptoms
Assessed by clinic staff. For a given sign or symptom, each subject's reactogenicity will be counted once under the maximum severity for each injection/ vaccination.
14 days following each vaccination
Number 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 and Pediatric Adverse Events, Corrected Version 2.1 (exceptions apply).
Through week 64
Number 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 and Pediatric Adverse Events, Corrected Version 2.1 (exceptions apply).
Through week 64
Number 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 and Pediatric Adverse Events, Corrected Version 2.1 (exceptions apply).
Through week 64
Number of AEs leading to early participant withdrawal or permanent discontinuation
Adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 (exceptions apply).
Through week 64
Frequency of CD4-bs-specific B cells
Measured by flow cytometry analysis
Through week 27
Frequency of VRC01-like BCR sequences
Determined by variable heavy chain domain (VH)/variable light chain domain (VL) sequencing of sorted B cells
Through week 27
Secondary Outcomes (22)
Response rate of Env-specific serum IgG binding antibodies.
Through week 27
Magnitude of Env-specific serum IgG binding antibodies.
Through week 27
Epitope-specificity of Env-specific serum IgG binding antibodies.
Through week 27
Avidity of Env-specific serum IgG binding antibodies.
Through week 27
Frequency of CD4-bs B cells and BCR sequences of isolated CD4-bs and VRC01-class memory B cells induced post-immunization with the traditional bolus dosing versus the fractionated dose delivery approach.
Through week 27
- +17 more secondary outcomes
Study Arms (7)
Bolus Delivery, Group 1: First injection - Medium dose, Final injection - Lower dose
EXPERIMENTALThe Bolus Delivery Arm Group 1 will receive injections at 2 visits scheduled 3 months apart. At each injection visit the patient will get one dose divided into 2 injections - one in the deltoid muscle of each arm.
Bolus Delivery, Group 2: First injection - Medium dose, Final injection - Higher dose
EXPERIMENTALThe Bolus Delivery Arm Group 2 will receive injections at 2 visits scheduled 3 months apart. At each injection visit the patient will get one dose divided into 2 injections - one in the deltoid muscle of each arm.
Bolus Delivery, Group 3: First injection - Placebo, Final injection - Placebo
PLACEBO COMPARATORThe Bolus Delivery Arm Group 2 will receive injections at 2 visits scheduled 3 months apart. At each injection visit the patient will get one dose divided into 2 injections - one in the deltoid muscle of each arm.
Fractionated Delivery, Group 1: First injection - Medium dose, Final injection - Lower dose
EXPERIMENTALThe first dose for the Fractionated Delivery Arm Group 1 will be divided into 6 smaller amounts (2 visits per week for 3 weeks). The second dose will be given about 3 months later and will be given all at once. At each injection visit for the first dose, the patient will get one amount divided into 2 injections - one in the deltoid muscle of each arm.
Fractionated Delivery, Group 2: First injection - Medium dose, Final injection - Higher dose
EXPERIMENTALThe first dose for the Fractionated Delivery Arm Group 2 will be divided into 6 smaller amounts (2 visits per week for 3 weeks). The second dose will be given about 3 months later and will be given all at once. At each injection visit for the first dose, the patient will get one amount divided into 2 injections - one in the deltoid muscle of each arm.
Fractionated Delivery, Group 3: First injection - Placebo, Final injection - Placebo
PLACEBO COMPARATORThe first dose for the Fractionated Delivery Arm Group 2 will be divided into 6 smaller amounts (2 visits per week for 3 weeks). The second dose will be given about 3 months later and will be given all at once. At each injection visit for the first dose, the patient will get one amount divided into 2 injections - one in the deltoid muscle of each arm.
Optional Boost Regimen with BG505
EXPERIMENTALSOSIP.GT1.1 gp140
Interventions
Administered via injection as a split dose into the deltoid muscle (both left and right).
Administered via injection as a split dose into the deltoid muscle (both left and right).
Administered via injection as a split dose into the deltoid muscle (both left and right).
A soluble, cleavage-competent, trimeric HIV-1 envelope glycoprotein gp140 formulated at 2 mg/mL, 0.55 mL per vial, in 20 mM Tris, 100 mM NaCl, pH 7.5 will be admixed with 3M-052-AF (5 mcg) + Alum (500 mcg
Administered via injection as a split dose into the deltoid muscle (both left and right).
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 any questionnaire items answered incorrectly.
- years old, inclusive, on day of enrollment.
- Available for clinic follow-up through the last clinic visit, willing to under go lymph node fine needle aspiration, and willing to be contacted 12 months after the last vaccine administration.
- 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:
- ≥ 11.0 g/dL for volunteers who were assigned female sex at birth
- ≥ 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
- ≥ 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.
- +8 more criteria
You may not qualify if:
- Volunteer who is breast-feeding or pregnant.
- Morbid Obesity. Enrollment of individuals with body mass index (BMI) ≥40, who the site investigator assesses are in good health, may be considered by PSRT on a case-by-case basis.
- International normalized ratio (INR) \>1.2.
- Previous or current recipient of an investigational HIV vaccine (previous placebo recipients are not excluded).
- Receipt of non-HIV experimental vaccine(s) received within the last 1 year. Exceptions may be made by the PSRT for vaccines that have subsequently undergone licensure or Emergency Use Authorization by the FDA or, if outside the United States, by the national regulatory authority or World Health Organization. For volunteers who have received control/placebo in an experimental vaccine trial, the PSRT will determine eligibility on a case-by-case basis.
- Systemic glucocorticoid use equal to or greater than prednisone 10 mg/day within 3 months prior to enrollment, other systemic medication use likely to impair immune response to vaccine in the opinion of the site investigator, or congenital or acquired immunodeficiency.
- 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 monoclonal antibody.
- Receipt of any live replicating vaccine within 4 weeks prior to enrollment. For receipt of ACAM2000 vaccine \>28 days prior with a vaccination scab still present.
- 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, including imidazoquinolone (eg, imiquimod).
- Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
- Idiopathic urticaria within the past year.
- Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions).
- Asplenia or functional asplenia.
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Alabama CRS
Birmingham, Alabama, 35222, United States
Bridge HIV CRS
San Francisco, California, 94102, United States
The Ponce de Leon Center CRS
Atlanta, Georgia, 30308-2012, United States
Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
Boston, Massachusetts, 02115-6110, United States
Columbia P&S CRS
New York, New York, 10032, United States
Seattle Vaccine and Prevention CRS
Seattle, Washington, 98104, United States
Related Publications (1)
Libera M, Caputo V, Laterza G, Moudoud L, Soggiu A, Bonizzi L, Diotti RA. The Question of HIV Vaccine: Why Is a Solution Not Yet Available? J Immunol Res. 2024 Apr 8;2024:2147912. doi: 10.1155/2024/2147912. eCollection 2024.
PMID: 38628675DERIVED
Study Officials
- STUDY CHAIR
Hyman Scott, MD
University of California, San Francisco
- STUDY CHAIR
Kristen Cohen, MD
Fred Hutch Cancer Center, Seattle, WA
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Masking Details
- Whether a participant receives a bolus dose or fractionated dose will be known, but randomization will occur within a given arm and both participants and clinicians will be blinded within a given arm.
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 15, 2022
First Posted
July 22, 2022
Study Start
August 22, 2022
Primary Completion
December 23, 2025
Study Completion (Estimated)
May 21, 2026
Last Updated
April 13, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share