A Phase 1 Open-label, Non-randomized, Clinical Trial to Evaluate the Safety and Immunogenicity of Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env (VRIPRO) in Adult Participants Who Previously Participated in HVTN 706
The clinical schedule will consist of 3 injections of CD40.HIVRI.Env (VRIPRO) at weeks 0, 4, and 24.40 volunteers without HIV and in overall good health, aged 18 to 60 years, who previously participated in the HVTN 706 trial.
• Formerly participated in HVTN 706 study as active vaccine arm or placebo recipient (those enrolled in the active vaccine arm of HVTN 706 must have received all 4 vaccinations according to the HVTN 706 protocol).
• Demonstrates an understanding of the study and is able and willing to complete the informed consent process.
• 18 to ≤ 60 years old, on day of enrollment.
• Available for clinic follow-up through the last clinic visit, willing to undergo FNA, and willing to be contacted 12 months after the last study-product administration.
• 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 318 (Protocol Safety Review Team) PSRT are required prior to enrollment into HVTN 318. Previous enrollment in HVTN 706 study is a requirement, per inclusion criteria 1.
• 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 judgement of the site investigator.
• Agrees to discuss the potential for HIV acquisition and agrees to prevention counseling.
• Hemoglobin (Hgb):
‣ ≥11.0 g/dL for women
⁃ ≥13.0 g/dL for men
⁃ If receiving exogenous hormones for more than 6 consecutive months with dosing equivalent to parenteral testosterone ≥1000 mg every 12 weeks or estradiol valerate ≥2 mg/week, determine hemoglobin eligibility based on the exogenous hormone reported.
⁃ White blood cell (WBC) count = 2,500 to 12,000/mm\^3 (WBC over 12,000/mm\^3 is not exclusionary if further evaluation shows general good health and if PSRT approval is granted).
⁃ Platelets = 125,000 to 550,000/mm\^3.
⁃ Alanine aminotransferase (ALT) \< 2.5 x upper limit of institutional reference range.
⁃ Serum creatinine ≤ 1.1 x upper limit of normal (ULN) based on the institutional normal range.
⁃ Systolic blood pressure of 90 to \< 140 mmHg and diastolic blood pressure of 50 to \< 90 mmHg at screening visit. The average blood pressure between the screening visit and the enrollment visit must be below 140 mmHg systolic and 90 mmHg diastolic. A single measurement ≥ 160 systolic mmHg or 100 mmHg diastolic during the current study evaluation is exclusionary.
⁃ Negative HIV test results by one of the following options:
∙ For participants who received study product under HVTN 706
⁃ A negative result from a HVTN HIV Diagnostic Testing Laboratory within 14 days prior to enrollment (see HVTN 318 HIV testing SSP for additional details); or
• A negative result from a non-HVTN laboratory following the external guidance for non-HVTN laboratories within 14 days prior to enrollment (external laboratory guidance for non-HVTN laboratories can be found in the guidance document, HIV Infection and VISP/R Status Diagnostic Testing at External (non-HVTN Laboratories).
‣ For participants at who received placebo under HVTN 706
⁃ A negative US Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA); or a chemiluminescent microparticle immunoassay (CMIA); or
• A negative result on 2 different HIV rapid tests (one of these rapid tests must be FDA approved)
⁃ Negative for anti-Hepatitis C virus (HCV) Abs (anti-HCV) or negative HCV nucleic acid test (NAT) if anti-HCV antibodies (Abs) are detected.
⁃ Negative for Hepatitis B surface antigen (Ag).
⁃ Women with pregnancy potential:
∙ Must have a negative β-HCG pregnancy test (urine or serum) on day of enrollment.
‣ Must agree to use effective means of contraception from at least 21 days prior to enrollment until 8 weeks after their last scheduled vaccination. See Appendix D.
‣ Women who have had a total hysterectomy, bilateral oophorectomy, or bilateral salpingectomy Consider including the cyan-highlighted parenthetical for product-specific reasons: (verified by medical records) or menopause (no menses for ≥1 year) are not required to undergo pregnancy testing.
⁃ Female volunteers 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.