Dose Escalation Safety Study of TMB-365 in HIV-1 Infected Participants

This phase 1, randomized, double-blinded, placebo-controlled, sequential single dose escalation study will evaluate the safety, tolerability and pharmacokinetic (PK) parameters of TMB-365 administered via intravenous infusion (IV) to HIV-1 infected participants at one of three successively increasing dose levels: 400 mg, 800 mg, and 1600 mg. Each participant will be monitored for 10 weeks post-administration. All participants will be expected to participate in PK sampling during Weeks 1, 4, 5, and 6. Beginning with the lowest dosage group, a Data Monitoring Committee (DMC) will review available data after four participants have completed two weeks of post-dose follow-up to determine if dosing of the next dosage group may proceed. If no dose limiting toxicities (DLTs) emerge, defined as a single Grade 4 or two of the same Grade 3 clinical or laboratory adverse events deemed possibly, probably or definitely related to the study drug, or a serious adverse event deemed possibly, probably or definitely related to the study drug as graded by the DAIDS Table for Grading Severity of Adult and Pediatric Adverse Events Version 2.1, then dosing of the next higher dose group will be permitted. Dosing in the highest dose group will begin after four of the eight participants in second group have successfully completed the scheduled study drug administration and two weeks of follow-up, and those data, along with all available data from the initial dose group have been reviewed by the DMC and no DLTs or SAEs as defined above are identified. All participants may initiate standard combination antiretroviral therapy six weeks after receiving the study drug.