A Phase 1 Randomized Study to Evaluate the Safety, Tolerability, and Immunogenicity of Ranging Doses of ALFQ Adjuvant in a Candidate HIV Vaccine Containing A244 and B.65321
This study will evaluate the safety and tolerability (including reactogenicity) of candidate vaccine A244/B.63521 with Army Liposome Formulation (ALF) mixed with the saponin QS-21(Quillaja saponaria-21) (ALFQ) adjuvant. The purpose of this phase I randomized, double-blind clinical trial is to optimize vaccine adjuvant ALFQ dosing by assessing safety, reactogenicity, and immunogenicity. Safety and tolerability will be assessed with both clinical and laboratory monitoring. Sixty human immunodeficiency virus (HIV) negative participants will be enrolled to one of three arms. Vaccinations via intramuscular (IM) injection will occur at months 0, 1, and 2. All participants will receive A244 and B.63521 (300 micrograms of each). In addition, Arm 1 will receive 200 micrograms of ALFQ. Arm 2 will receive 100 micrograms of ALFQ. Arm 3 will receive 50 micrograms of ALFQ.
• Healthy adults between the ages 18-55 years (inclusive)
• Must be at low risk for HIV infection per investigator assessment and using the study risk assessment tool.
• Able and willing to provide written, informed consent
• Able and willing to comply with all research requirements, in the opinion of the Investigator
• Agreement to refrain from blood donation during the course of the study
• Minimum body weight of 110 pounds (lbs) (50kg)
• Laboratory Criteria within 30 days before enrollment:
∙ Hemoglobin ≥ 12.0 g/dL for women; ≥ 12.5 g/dL for men
‣ White Blood Cell count = 3,500-10,800 cells/mm3
‣ Platelets ≥140,000/mm3 and ≤ 450,000/mm3
‣ Alanine aminotransferase (ALT; SGPT) \<1.25 x Upper Limit of Normal (ULN)
‣ Serum creatinine ≤ 1.25 x institutional upper limit of the reference range
‣ Negative HIV testing (HIV Ab / antigen 4th generation screen with reflex confirmatory RNA testing)
‣ Negative HBsAg and hepatitis C antibody testing Note: As above, Grade 1 lab abnormalities detected on screening may be repeated at PI discretion. Persistent Grade 1 abnormalities that are felt to represent the non-pathologic baseline for the subject will be documented before a subject is enrolled in the trial and are allowable per discretion of the PI.
• Birth control requirements:
• All participants assigned female at birth must meet one of the following 2 criteria:
‣ No reproductive potential due to post-menopausal status (12 months of natural \[spontaneous\] amenorrhea) or hysterectomy, bilateral oophorectomy, or tubal ligation
‣ People of childbearing potential should agree to practice highly effective contraception at least 30 days before enrollment and through 3 months post-last vaccination, using one of the following methods: condoms (male or female) with spermicide; diaphragm, or cervical cap with spermicide; intrauterine device; contraceptive pills, patch, injection, intravaginal ring or other FDA-approved contraceptive method; male partner has previously undergone a vasectomy; abstinence
‣ All participants are encouraged to engage in safe sex practices to prevent HIV acquisition
• For all participants assigned female at birth, except those with a history of hysterectomy or bilateral oophorectomy, a negative β-human chorionic gonadotropin (HCG) pregnancy test (urine) on the day of enrollment and each vaccination day is required. Because tubal ligations have a failure rate that is not insignificant, and because 12 months of spontaneous amenorrhea can be a result of polycystic ovarian syndrome and does not completely preclude pregnancy, a negative β- HCG pregnancy test at enrollment and on each vaccination day is also required for participants assigned female at birth with a history of either of these).
⁃ No plans to travel outside the Washington DC metro area (DC, Maryland, and Virginia) that would prevent compliance with planned study visits
⁃ Test of Understanding (TOU) (minimum passing score of 80% with 2 attempts permitted)