The DART DELIVER-02 Study

This study is a phase 1, pilot, open-label study of MGD014 in combination with MGD020 in PWH on ART. The study is designed to characterize the safety, tolerability, pharmacokinetics (PK), and immunogenicity of the study drugs alone, and in combination with an latency reversal agent (LRA) or a TTI. Participants will be enrolled, undergo an initial evaluation and baseline sample collections, and then be randomized to 1 of 3 arms as follows: Arm A: Continue baseline ART and receive biweekly MGD014/ MGD020 infusions at Day 0, weeks 2, 4 and 6. Arm B: Initiate biweekly MGD014/ MGD020 infusions at Day 0 and undergo a TTI from Day 4 to week 8. Arm C: Continue baseline ART, receive MGD014/ MGD020 infusions at Day 0, week 2, 8, and 10 in combination with VOR 400mg every 72 hours from Day 0 to week 4 and week 8-12 The study design will allow comparison of the impact of MGD014/MGD020 administration with continued ART alone, to MGD014/MGD020 administration with two different methods of latency reversal, 1) VOR, a latency reversal agent, and 2) TTI. All participants will receive a total of 4 doses of MGD014/MGD020 at 300 mcg/kg administered as intravenous infusion. In Arms A and B, MGD014/MGD020 will be infused every 2-3 weeks. In Arm C, participants will receive two doses of MGD014/MGD020 at weeks 0 and 2, then again at weeks 8 and 10.In Arm C, participants will receive VOR 400 mg orally every 72 hours for 10 doses from Day 0 to week 4, and a second cycle of VOR 400 mg orally every 72 hours for 10 doses from week 8 to 12. Study participants will have regular clinical assessments, including safety labs, viral load measurements, and CD4+ cell counts. Specimens will be stored for virologic and immunologic studies, including but not limited to comprehensive assessments of viral integrants, cell-associated HIV RNA, PK of MGD014/MGD020, and biomarkers of VOR exposure. An independent safety monitor will provide study oversight and evaluate cumulative safety and other clinical data at regular intervals.