A Phase 1 Clinical Trial to Evaluate the Safety, Pharmacokinetics, and in Vitro Neutralization of ePGT121v1-LS, PGDM1400LS, and VRC07-523LS Administered in Multiple Doses and Routes to Adult Participants Without HIV-1
This study is testing a lab-made antibody called ePGT121v1-LS that targets a specific part of HIV. Researchers will give it by vein (IV) and under the skin (SC), both on its own and together with two other antibodies, VRC07-523LS and PGDM1400LS, which target different parts of the virus. They will assess safety and side effects, determine the right dose, study how the body processes the drug (pharmacokinetics or PK), and measure how well it neutralizes HIV in the blood (serum neutralizing activity). The expectation is that ePGT121v1-LS, whether given alone or with PGDM1400LS and VRC07-523LS, by IV or SC, will be safe in generally healthy adults and that the antibodies will not interfere with each other when used together. Approximately 83 volunteers in overall good health and without HIV-1 will be enrolled into two parts (A and B). Part A has six groups. In Groups 1-3, participants will get ePGT121v1-LS given by IV at one of three dose levels: 5 mg/kg, 20 mg/kg, or 40 mg/kg. In Groups 4-6, participants will receive three antibodies-first ePGT121v1-LS, then PGDM1400LS and VRC07-523LS-given by IV at two separate visits that are 24 weeks apart. The total study duration for participants in Part A is 48 weeks of scheduled clinic visits. Part B has two groups. In Group 7, people will get ePGT121v1-LS as SC shots at two visits 12 weeks apart. Each visit will give a total of 375 mg, split into three injections of 125 mg each. In Group 8, people will also have two visits 12 weeks apart and will receive three antibodies as SC shots in this order: first ePGT121v1-LS (125 mg), then PGDM1400LS (100 mg), and then VRC07-523LS (100 mg). The total study duration for participants in Part B is 24 weeks of scheduled clinic visits.
• Age 18 to 55 years.
• Can visit a participating clinic and is willing to stay in the study for its full duration.
• Understands the study and is able and willing to give informed consent.
• Agrees not to join another experimental study until the final required clinic visit.
• In good overall health based on medical history, physical exam, and screening lab tests.
• Willing to receive HIV test results.
• Willing to discuss personal risk of getting HIV and to have HIV prevention counseling.
• Judged by clinic staff to have a low risk of getting HIV and agrees to avoid higher risk behaviors through the last clinic visit.
• Hemoglobin levels:
‣ Women: at least 11.0 g/dL
⁃ Men: at least 13.0 g/dL
⁃ White blood cell count between 2,500 and 12,000 cells/mm³.
⁃ White blood cell differential is normal or acceptable to clinic staff.
⁃ Platelet count between 125,000 and 550,000 cells/mm³.
⁃ ALT (liver enzyme) less than 1.25 times the lab's upper limit of normal.
⁃ Creatinine (kidney test) less than 1.1 times the lab's upper limit of normal.
⁃ Negative tests for HIV 1 and HIV 2.
⁃ Negative hepatitis B surface antigen.
⁃ Negative hepatitis C antibody, or a negative HCV PCR if the antibody test is positive.
⁃ Urine protein is negative or only trace.
⁃ If a woman who could become pregnant: negative pregnancy test within 72 hours before the first study treatment. Women with a documented total hysterectomy, both ovaries removed, both fallopian tubes removed, or menopause (no periods for at least 1 year) do not need pregnancy testing.
⁃ Women who could become pregnant agree to use effective birth control for sex that could lead to pregnancy starting at least 21 days before enrollment and continuing through the last study visit.
⁃ Women who could become pregnant also agree not to try to become pregnant using methods like egg retrieval, artificial insemination, or in vitro fertilization starting at least 21 days before enrollment and continuing through the last clinic visit.