A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of the V2 Apex-Directed Immunogens DV201P-RNA and DV202B1-RNA in Adult Participants Without HIV
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 40
- Locations
- 14
- Primary Endpoint
- Local reactogenicity for a minimum of 14 days following receipt of any study vaccine
Overview
Brief Summary
This is a phase 1, multicenter, open-label, dose escalation, first-in-human (FIH) trial to evaluate the safety and immunogenicity of DV201P-RNA and DV202B1-RNA, immunogens designed to induce HIV-1 envelope (Env) V2 apex-specific broadly neutralizing antibodies (V2 apex bnAbs). Both vaccines consist of a modified mRNA encapsulated in lipid nanoparticles (LNP) that when translated in cells produces HIV-1 Env gp150 transmembrane trimers. The trial will enroll adult volunteers without HIV and in overall good health.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Demonstrates an understanding of the study and is able and willing to complete the informed consent process.
- •At least 18 years old at screening and up to 55 years old on day of enrollment.
- •Available for clinic follow-up through the last clinic visit.
- •Willing to undergo study procedures as outlined in the schedule of procedures (Appendix A).
- •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 322 PSRT are required prior to enrollment into HVTN
- •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.
- •Agrees to discuss their potential for HIV acquisition and agrees to HIV prevention counseling.
- •Hemoglobin (Hgb):
- •11.0 g/dL for women
Exclusion Criteria
- •Women who are breastfeeding or pregnant.
- •Body mass index (BMI) ≥
- •Enrollment of individuals with BMI ≥40 who are in good health, as assessed by the site investigator, 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 or prednisone dose of ≥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 PSRT approval.
- •Receipt of any of the following within 4 weeks prior to enrollment:
- •Live replicating vaccine
Arms & Interventions
Group 1: 50 mcg
DV201P-RNA (50 mcg) at weeks 0 and 12.
Followed by:
DV202B1-RNA (50 mcg) at weeks 24 and 40.
Intervention: DV201P-RNA (Biological)
Group 1: 50 mcg
DV201P-RNA (50 mcg) at weeks 0 and 12.
Followed by:
DV202B1-RNA (50 mcg) at weeks 24 and 40.
Intervention: DV202B1-RNA (Biological)
Group 2: 100 mcg
DV201P-RNA (100 mcg) at weeks 0 and 12.
Followed by:
DV202B1-RNA (100 mcg) at weeks 24 and 40.
Intervention: DV201P-RNA (Biological)
Group 2: 100 mcg
DV201P-RNA (100 mcg) at weeks 0 and 12.
Followed by:
DV202B1-RNA (100 mcg) at weeks 24 and 40.
Intervention: DV202B1-RNA (Biological)
Group 3: 150 mcg
DV201P-RNA (150 mcg) at weeks 0 and 12.
Followed by:
DV202B1-RNA (150 mcg) at weeks 24 and 40.
Intervention: DV201P-RNA (Biological)
Group 3: 150 mcg
DV201P-RNA (150 mcg) at weeks 0 and 12.
Followed by:
DV202B1-RNA (150 mcg) at weeks 24 and 40.
Intervention: DV202B1-RNA (Biological)
Group 4: TBD*
DV202B1-RNA (50 mcg or 100 mcg or 150 mcg; highest dose that is determined to be safe and well tolerated from Groups 1-3) at weeks 0 and 12.
Intervention: DV202B1-RNA (Biological)
Outcomes
Primary Outcomes
Local reactogenicity for a minimum of 14 days following receipt of any study vaccine
Time Frame: Day 0 (vaccination) through 14 days post-vaccination; at days 15, 99, 183, and 295
Systemic reactogenicity for a minimum of 14 days following receipt of any study vaccine
Time Frame: Day 0 (vaccination) through 14 days post-vaccination; at days 15, 99, 183, and 295
Serious adverse events (SAEs), medically attended AEs (MAAEs), AEs of special interest (AESIs), and AEs leading to withdrawal/discontinuation collected throughout study; additionally, all AEs collected for 30 days after receipt of any study vaccination
Time Frame: From informed consent through end of study for SAEs, MAAEs, AESIs, and AEs leading to withdrawal/discontinuation; all AEs for 30 days after receipt of any study vaccination
Response rate of V2 apex-specific IgG+ B cells as assessed by flow cytometry 2 weeks after second vaccination
Time Frame: 2 weeks after the second vaccination (Day 99)
Frequency of V2 apex-specific IgG+ B cells as assessed by flow cytometry 2 weeks after second vaccination
Time Frame: 2 weeks after the second vaccination (Day 99)
Response rate of differential serum Ab neutralization of precursor detection viruses and corresponding epitope knock-out mutant forms of the viruses, as measured by the TZM-bl assay at 2 weeks after second vaccination
Time Frame: 2 weeks after the second vaccination (Day 99)
Magnitude of differential serum Ab neutralization of precursor detection viruses and corresponding epitope knock-out mutant forms of the viruses, as measured by the TZM-bl assay at 2 weeks after second vaccination
Time Frame: 2 weeks after the second vaccination (Day 99)
Response rate of serum IgG binding antibodies to autologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA) at 2 weeks after second vaccination
Time Frame: 2 weeks after the second vaccination (Day 99)
Magnitude of serum IgG binding antibodies to autologous HIV Env stabilized trimers, as assessed by BAMA at 2 weeks after second vaccination
Time Frame: 2 weeks after the second vaccination (Day 99)
Response rate of differential serum Ab neutralization of precursor detection viruses and corresponding epitope knock-out mutant forms of the viruses as measured by TZM-bl pseudovirus assay 2 weeks after the third and fourth vaccinations (Groups 1-3)
Time Frame: 2 weeks after the third vaccination and 2 weeks after the fourth vaccination (Days 183 and 295)
Magnitude of differential serum Ab neutralization of precursor detection viruses and corresponding epitope knock-out mutant forms of the viruses as measured by TZM-bl pseudovirus assay 2 weeks after third and fourth vaccinations (Groups 1-3)
Time Frame: 2 weeks after the third vaccination and 2 weeks after the fourth vaccination (Days 183 and 295)
Secondary Outcomes
- Response rate of serum IgG binding to HIV Env-stabilized trimers as assessed by BAMA at 2 weeks after third and fourth vaccinations (Groups 1-3)(2 weeks after the third vaccination and 2 weeks after the fourth vaccination (Days 183 and 295))
- Magnitude of serum IgG binding to HIV Env-stabilized trimers as assessed by BAMA at 2 weeks after third and fourth vaccinations (Groups 1-3)(2 weeks after the third vaccination and 2 weeks after the fourth vaccination (Days 183 and 295))
- V2 specificity of serum IgG binding to HIV Env-stabilized trimers as assessed by BAMA at 2 weeks after third and fourth vaccinations (Groups 1-3)(2 weeks after the third vaccination and 2 weeks after the fourth vaccination (Days 183 and 295))
- Breadth of serum IgG binding to HIV Env-stabilized trimers as assessed by BAMA at 2 weeks after third and fourth vaccinations (Groups 1-3)(2 weeks after the third vaccination and 2 weeks after the fourth vaccination (Days 183 and 295))
- Response rate of V2 apex-specific IgG+ B cells as assessed by flow cytometry at 2 weeks after third and fourth vaccinations (Groups 1-3)(2 weeks after the third vaccination and 2 weeks after the fourth vaccination)
- Frequency of V2 apex-specific IgG+ B cells as assessed by flow cytometry at 2 weeks after third and fourth vaccinations (Groups 1-3)(2 weeks after the third vaccination and 2 weeks after the fourth vaccination)
- Frequency of V2 apex broadly neutralizing antibody (bnAb) lineage sequences as measured by B-cell receptor (BCR) single cell sequencing of V2 apex-specific IgG+ B cells(2 weeks after the fourth vaccination for Groups 1-3; 2 weeks after the second vaccination for Group 4)
- Epitope-specific response rates as measured by EMPEM at 2 weeks after vaccination(2 weeks after the fourth vaccination for Groups 1-3; 2 weeks after the second vaccination for Group 4)
- Response rate of serum antibody neutralization of heterologous HIV-1 strains as measured by TZM-bl assay at 2 weeks after vaccination(Groups 1-3: 2 weeks after the second vaccination and 2 weeks after the fourth vaccination, Group 4: 2 weeks after the second vaccination)
- Magnitude of serum antibody neutralization of heterologous HIV-1 strains as measured by TZM-bl assay at 2 weeks after vaccination(Groups 1-3: 2 weeks after the second vaccination and 2 weeks after the fourth vaccination, Group 4: 2 weeks after the second vaccination)