A Study of MGD020 Alone or Combined With MGD014 in Persons With HIV-1 on Antiretroviral Therapy

Study Overview
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Brief Summary
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Study CP-MGD020-01 is a phase 1, open-label, dose-escalation, and multi-dose expansion study of MGD020 as a single agent or in combination with MGD014 in persons with HIV-1 (PWH) on antiretroviral therapy (ART). The study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and pharmacodynamics (PD) of the study drugs. The study consists of 3 parts (Part 1A, Part 1B, and Part 2). The participant's standard of care ART regimen is continued throughout the study period. MGD020 is a bispecific DART® molecule that binds CD3 and gp41 subunit of HIV-1 envelope. MGD014 is a bispecific DART® molecule that binds CD3 and gp120 subunit of HIV-1 envelope. These DART molecules redirect CD3+ T lymphocytes to kill HIV-1-infected CD4+ T cells. Part 1A evaluates groups of participants given a single dose of MGD020. A 2-week safety period is observed prior to escalation to the next dose level. Dose escalation continues until either the maximum tolerated dose (MTD) or maximum administered dose (MAD) is determined. Part 1B begins after the end of Part 1A. Part 1B evaluates groups of participants given a single dose of the MGD020 MTD or MAD from Part 1A and a fixed dose of of MGD014. The first group will be treated with a single dose of MGD020, at a dose determined to be one dose lower than the single-agent MTD/MAD from Part 1A, and a single 300 mcg/kg dose of MGD014. Dose escalation proceeds until either the MTD or MAD is determined. Part 2 begins Part 1B. Part 2 is a multi-dose expansion group. Each participant will receive the MTD or MAD of MGD020 and MGD014 from Part 1B, administered every 2 weeks (Q2W) for 3 combination doses over 4 weeks. Up to 6 participants may be enrolled in Part 2.

Official Title
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A Phase 1 Study of MGD020 as a Single Agent or in Combination With MGD014 in Persons With HIV-1 on Antiretroviral Therapy

Conditions
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Human Immunodeficiency Virus I Infection, Immunodeficiency Virus Type 1, Human, Human Immunodeficiency Virus Type 1

Intervention / Treatment
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* Biological: MGD020
* Biological: MGD014


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years and ≤ 70 years of age and able to provide informed consent HIV-1 infection documented by rapid HIV test or HIV enzyme or chemiluminescence immunoassay and confirmed by a different second test. Plasma HIV-1 RNA viral load < 50 copies/mL at 2 time points within 24 months prior to screening (1 time point within 12 months prior to screening), and < 50 copies/mL at screening, and Not ≥ 50 copies/mL on 2 consecutive time points within 24 months nor > 1000 copies/mL at any time within 6 months prior to screening On continuous antiretroviral therapy (ART) for at least 24 months prior to screening and must continue ART throughout the study. CD4 cell count > 350 cells/mm3 at screening Acceptable laboratory values related to bone marrow, kidney and liver function. Individuals of childbearing potential must agree to use highly effective forms of contraception throughout the study through 4 months after the last dose of MGD024. Exclusion Criteria: History of any HIV-1 vaccine or HIV-1 immunotherapy, except MGD014 or MGD020, within 6 months prior to screening. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient. Active viral, bacterial, or systemic fungal infection requiring intravenous antibiotic, antiviral, or antifungal treatment within 7 days prior to the initiation of study drug. Active coronavirus disease 19 (COVID-19)/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participation in another investigational clinical research study within 60 days prior to screening. History of virologic failure on an ART regimen containing FDA-approved HIV-1 entry inhibitors (maraviroc, enfuvirtide, and/or ibalizumab). Virologic failure is defined as a confirmed plasma HIV-1 RNA ≥ 150 copies/mL following assessment of drug adherence, repeat HIV-1 RNA testing with continued treatment, and/or resistance testing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1A: Dose level 1<br>Single dose MGD020 | Biological: MGD020<br>* MGD020 is a bispecific DART molecule that binds CD3 and gp41 subunit of HIV-1 envelope.<br>|
| Experimental: Part 1A: Dose level 2<br>Single dose MGD020 | Biological: MGD020<br>* MGD020 is a bispecific DART molecule that binds CD3 and gp41 subunit of HIV-1 envelope.<br>|
| Experimental: Part 1A: Dose level 3<br>Single dose MGD020 | Biological: MGD020<br>* MGD020 is a bispecific DART molecule that binds CD3 and gp41 subunit of HIV-1 envelope.<br>|
| Experimental: Part 1A: Dose level 4<br>Single dose MGD020 | Biological: MGD020<br>* MGD020 is a bispecific DART molecule that binds CD3 and gp41 subunit of HIV-1 envelope.<br>|
| Experimental: Part 1A: Dose level 5<br>Single dose MGD020 | Biological: MGD020<br>* MGD020 is a bispecific DART molecule that binds CD3 and gp41 subunit of HIV-1 envelope.<br>|
| Experimental: Part 1A: Dose level 6<br>Single dose MGD020 | Biological: MGD020<br>* MGD020 is a bispecific DART molecule that binds CD3 and gp41 subunit of HIV-1 envelope.<br>|
| Experimental: Part 1B: MTD/MAD -1 MGD020 and MGD014<br>Single dose MGD020 and MGD014 | Biological: MGD020<br>* MGD020 is a bispecific DART molecule that binds CD3 and gp41 subunit of HIV-1 envelope.<br>Biological: MGD014<br>* MGD014 is a bispecific DART molecule that binds CD3 and gp120 subunit of HIV-1 envelope.<br>|
| Experimental: Part 1B: MTD/MAD MGD020 and MGD014<br>Single dose MGD020 and MGD014 | Biological: MGD020<br>* MGD020 is a bispecific DART molecule that binds CD3 and gp41 subunit of HIV-1 envelope.<br>Biological: MGD014<br>* MGD014 is a bispecific DART molecule that binds CD3 and gp120 subunit of HIV-1 envelope.<br>|
| Experimental: Part 2: MGD020 and MGD014<br>Multiple doses of MGD020 and MGD014 | Biological: MGD020<br>* MGD020 is a bispecific DART molecule that binds CD3 and gp41 subunit of HIV-1 envelope.<br>Biological: MGD014<br>* MGD014 is a bispecific DART molecule that binds CD3 and gp120 subunit of HIV-1 envelope.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and types of adverse events (AEs), including serious adverse events (SAEs), and AEs leading to treatment discontinuation in participants receiving MGD020 alone in Part 1A | Observation of side effects determines the highest safe dose for further study | Throughout the study, up to 43 days | 
| Number and types of adverse events (AEs), including serious adverse events (SAEs), and AEs leading to treatment discontinuation in participants receiving MGD020 and MGD014 in Part 1B. | Observation of side effects determines the highest safe dose for further study | Throughout the study, up to 43 days | 
| Number and types of adverse events (AEs), including serious adverse events (SAEs), and AEs leading to treatment discontinuation in participants receiving MGD020 and MGD014 in Part 2. | Observation of side effects determines the highest safe dose for further study | Throughout the study, up to 81 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration of MGD020 | The highest concentration of MGD020 at the end of the infusion | Study Day 1, 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 1, 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2 | 
| Maximum concentration of MDG014 | The highest concentration of MGD014 at the end of the infusion | Study Day 1, 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 1, 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2 | 
| Time to maximal concentration of MGD020 | The amount of time required to get maximum concentration of MGD020 | Study Day 1, 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 1, 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2 | 
| Time to maximal concentration of MGD014 | The amount of time required to get maximum concentration of MGD014 | Study Day 1, 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 1, 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2 | 
| Area under the concentration-time curve (AUC) of MGD020 | Total body exposure to MGD020 | Study Day 1, 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 1, 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2 | 
| AUC of MGD014 | Total body exposure to MGD014 | Study Day 1, 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 1, 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2 | 
| Trough concentration of MGD020 | The amount of MGD020 left after dosing | Study Day 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2 | 
| Trough concentration of MGD014 | The amount of MGD014 left after dosing | Study Day 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2 | 
| Half-life of MGD020 | The amount of time needed for the body to clear half of the dose of MGD020 | Study Day 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2 | 
| Half-life of MGD014 | The amount of time needed for the body to clear half of the dose of MGD021 | Study Day 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2 | 
| Volume of Distribution at steady state of MGD020 | This parameter measures how much of the drug remains in the bloodstream or is distributed to body tissues. | Study Day 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2 | 
| Volume of Distribution at steady state of MGD014 | This parameter measures how much of the drug remains in the bloodstream or is distributed to body tissues. | Study Day 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2 | 
| Clearance of MGD020 | Total body clearance of the drug from plasma of MGD020 | Study Day 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2 | 
| Clearance of MGD014 | Total body clearance of the drug from plasma of MGD014 | Study Day 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2 | 
| Change from baseline in serum cytokine levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, and TNF-α |  | Day 1, 2, and 8 Part 1A and 1B. Day 1, 2, 8, 15, and 29 in Part 2. | 
| Anti-drug antibody formation to MGD020 | Number of patients who develop antibodies against MDG020 | Day 1, 15, 29 and 43 in Part 1A and 1B. Day 1, 15, 29, and 78 in Part 2. | 
| Anti-drug antibody formation to MGD014 | Number of patients who develop antibodies against MDG014 | Day 1, 15, 29 and 43 in Part 1A and 1B. Day 1, 15, 29, and 78 in Part 2. |