| Protocol No: | ECCT/26/04/02 | Date of Protocol: | 13-01-2026 |
| Study Title: | IGHID12430/DELIVER-02 - A PHASE 1, OPEN LABEL,STUDY TO EVALUATE THE SAFETY AND TOLERABILITY OF MGD014 AND MGD020 WITH A LATENCY REVERSAL AGENT VERSUS TEMPORARY TREATMENT INTERRUPTION IN PERSONS WITH HIV-1 ON ANTIRETROVIRAL THERAPY |
| Study Objectives: |
Primary Objective
Evaluate the safety and tolerability of MGD014 and MGD020 (DARTs) administered intravenously (IV) in combination with the latency reversal approaches of a) a TTI versus b) VOR administered orally
Secondary Objective
1. Assess the PK of a) MGD020 in combination with MGD014
2. Assess immunogenicity (ADA) of MGD020 in combination with MGD014
3. Further characterize the safety and tolerability of MGD014 and MGD020 in combination with VOR or TTI
Exploratory Objectives
1. Explore markers of persistent HIV-1 infection
2. Assess serum cytokine levels
|
| Laymans Summary: |
HIV medication has changed Human Immunodeficiency Virus (HIV) from a deadly disease to a long-term health condition for the 37 million people with HIV (PWH) in the world with 1.4 million of those living in Kenya. However, HIV medications need to be taken for life, as stopping often leacells. To clear the infection, a DART molecule, which is like an antibody, can bind an HIV-infected cell and a T cell to recruit the T cell to recognize and attack the HIV-infected cell, hence the possibility of HIV elimination. This study will evaluate the safety and effect of combining DART molecules, called MGD014 and MGD020, with Vorinostat (VOR), which is a drug that activates the hidden virus by interfering with how it stays dormant, or with a TTI to reactivate “non-active” HIV within cells. The study will see if MDG014 and MGD020 can attack these cells in which HIV hides. The study will also look at how quickly the drugs are absorbed and metabolized in the body, which involves taking blood at certain time points after taking the drugs. Participants in Kenya will be assigned to 1 of 2 groups as follows: Arm A (all sites): Continue HIV medication and receive MGD014/MGD020 infusions at Day 0, weeks 2, 4 and 6. Arm B (Kenya sites only): Initiate MGD014/ MGD020 infusions at Day 0, weeks 2, 4, and 6 and undergo a TTI from Day 4 to week 8. Arm C will only enroll at UNC and will have participants continue their HIV medication and receive MGD014/ MGD020 infusions at Day 0, weeks 2, 8 and 10, in combination with VOR 400mg every 72 hours from Day 0 to week 4 and weeks 8-12. Participants will have regular clinical assessments, including blood draws for research testing and to monitor their health throughout the study. A total of 24 participants with HIV who are taking HIV medication and have very low levels of virus in their blood (HIV-1 RNA < 50 copies/mL) for 24 months prior to enrollment will be enrolled study wide; up to 8 participants will be enrolled in Kericho and up to 8 participants in Eldoret. Each participant will be in the study for approximately 30 weeks and will have 13 to 18 study visits, depending on which group they are assigned. The study will provide information on innovative therapies for HIV eradication.
|
| Abstract of Study: |
Antiretroviral therapy (ART) has transformed human immunodeficiency virus type 1 (HIV) from a fatal disease to a chronic condition, however ART must be taken life-long as interruption of therapy in people with HIV (PWH) typically results in viral rebound within weeks. Although antiretroviral therapy (ART) effectively suppresses viremia, ART does not eliminate the latent viral reservoir. Therefore, to enable PWH to cease ART, additional strategies are required. One approach to eradicate HIV infection is to expose latent, persistent HIV and eliminate exposed latently infected cells by an enhanced T-cell immune response. This can be done with a latency reversing agent (LRA) without interrupting ART or by a Temporary Treatment Interruption (TTI), during which ART is discontinued for a defined period. To clear infection after LRAs or during TTI, a bi-specific antibody that redirects cytolytic T cells to recognize and destroy HIV-infected cells that express HIV envelope (env) and CD3 T cells is a plausible cure strategy. MGD020 and MGD014 dual affinity retargeting (DART) molecules bind HIV-1 env and human CD3 antigen. The co-engagement of HIV-1-infected, env-expressing cells and CD3+ T cells mediated by these DART molecules induces cytolysis of HIV-1 infected cells. This study is a Phase 1, open label study designed to characterize the safety, tolerability, pharmacokinetics (PK), and immunogenicity of the study drugs alone, and in combination with the two different methods of latency reversal, a LRA and a TTI. Participants will be assigned to 1 of 2 arms, Arms A and B at Kericho CRC and MUCRC and Arms A and C at UNC. Arm A will continue baseline ART and receive biweekly MGD014/MGD020 infusions at Day 0, weeks 2, 4 and 6. Arm B will initiate biweekly MGD014/ MGD020 infusions at Day 0, weeks 2, 4, and 6 and undergo a TTI from Day 4 to week 8. Arm C will continue baseline ART and receive MGD014/ MGD020 infusions at Day 0, weeks 2, 8, and 10, in combination with Vorinostat (VOR) 400mg every 72 hours from Day 0 to week 4 and weeks 8-12. Participants will have regular clinical assessments, including safety labs, viral load measurements, and CD4+ cell counts. Specimens will be stored for virologic and immunological studies. A total of 24 participants with HIV on ART with plasma HIV-1 RNA < 50 copies/mL for 24 months prior to enrollment will be enrolled study wide, including up to 8 participants in Kericho and up to 8 participants in Eldoret. Each participant will be in the study for approximately 30 weeks. The study will provide information on innovative therapies on HIV eradication
|