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
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.
• 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 322.
• 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
⁃ 13.0 g/dL for men
⁃ White blood cell (WBC) count of 2,500 to 12,000/mm3. WBC over 12,000/mm3 is not exclusionary if further evaluation shows general good health and if PSRT approval is granted.
⁃ Platelet count of 125,000 to 550,000/mm3.
⁃ Alanine aminotransferase (ALT) \<2.5× the upper limit of institutional reference range.
⁃ Serum creatinine ≤1.1× the upper limit of normal (ULN) based on the institutional normal range.
⁃ Total measured serum calcium level \>8.5 mg/dL.
⁃ Systolic blood pressure of 90 to \<140 mm Hg and diastolic blood pressure of 50 to \<90 mm Hg at screening visit. The average blood pressure between the screening visit and the enrollment visit must be below 140 mm Hg systolic and 90 mmHg diastolic. A single measurement of ≥160 mm Hg systolic or ≥100 mm Hg diastolic during the current study evaluation is exclusionary.
⁃ HIV test results by one of the following options:
⁃ • Negative US Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA) or
⁃ • Negative results on two different brands of HIV rapid tests (one of which must be FDA-approved)
⁃ Negative for anti-Hepatitis C virus (HCV) Abs or negative HCV nucleic acid test (NAT) if anti-HCV Abs are detected.
⁃ Negative for Hepatitis B surface antigen (Ag).
⁃ For women 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 timepoint (see Appendix D).
⁃ • Must have a negative beta human chorionic gonadotropin (β-HCG) pregnancy test (urine or serum) on day of enrollment.
⁃ Note: Women who have had a total hysterectomy, bilateral oophorectomy, or bilateral salpingectomy (verified by medical records) or menopause (no menses for ≥1 year) are not required to undergo pregnancy testing.
⁃ Women of pregnancy potential 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 timepoint.