MGD014 in HIV-Infected Individuals on Suppressive Antiretroviral Therapy

Study Overview
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Brief Summary
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This is a Phase 1, open-label single-center study to determine the safety of MGD014 in participants with human immunodeficiency virus (HIV) infection on stable suppressive antiretroviral therapy (ART).

Detailed Description
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Eligible participants will be maintained on ART and receive either one infusion (Part 1) or multiple infusions of MGD014 (Part 2). Part 1 is a single ascending dose study with a 1+3 design for the first 2 dose cohorts, and a 3+3 design with staggered accrual for the 6 higher dose cohorts, with an aim of determining the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ascending doses up to either the Optimal Biologic Dose (OBD) or the maximum administered dose (MAD). Part 2 is a multi-dose expansion cohort with MGD014 administered at the OBD, as determined in Part 1. In Part 2, additional assessments on the effects of MGD014 on HIV latent infection parameters will be evaluated.

Official Title
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A Phase 1 Study to Evaluate the Safety, Immunologic and Virologic Responses of MGD014 Therapy in HIV-Infected Individuals on Suppressive Antiretroviral Therapy

Conditions
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HIV-1-infection

Intervention / Treatment
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* Biological: MGD014


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability and willingness of participant to provide written informed consent. HIV-1 infection, documented by any FDA-approved rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load. On a potent, stable, continuous ART regimen for ≥ 24 months prior to Screening. Plasma HIV-1 RNA < 50 copies/mL at two time points in the previous 12 months prior to screening (one time point can be screening) and never ≥ 50 copies/mL on 2 consecutive time points in the last 24 months. Adequate organ function based on acceptable laboratory parameters. Exclusion Criteria: Women of childbearing potential defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or menopause. History or other evidence of severe illness, immunodeficiency other than HIV, or any other condition that would make the potential participant unsuitable for study. History or other evidence of any condition or process for which signs or symptoms could be confused with reactions to MGD014. History of any HIV immunotherapy or HIV vaccine except for MGD014 within 12 months prior to screening. History of clinically significant cardiovascular disease, severe allergic reactions, malignancy (except non-melanoma skin cancer) within 5 years, seizure disorder within 2 years, organ/tissue transplant, autoimmune disease, unstable asthma, bleeding disorder. Evidence of active viral, or antifungal treatment within 7 days prior to the initiation of study drug Active, asymptomatic, or suspected COVID-19/SARS-CoV-2 infection. Active, untreated syphilis. Use of blood products, cytokine therapy, growth-stimulating factors, cytotoxic chemotherapy or investigational therapy within 90 days. Current use of the antivirals maraviroc and/or enfuvirtide. Any vaccination with exception of flu vaccine within 30 days of screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Interventional Model Description: Open-label dose-escalation study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MGD014 0.1 micrograms/kilogram (mcg/kg)<br>a single 2-hour infusion | Biological: MGD014<br>* HIV-1 x CD3 bispecific DART molecule<br>|
| Experimental: MGD014 0.3 mcg/kg<br>a single 2-hour infusion | Biological: MGD014<br>* HIV-1 x CD3 bispecific DART molecule<br>|
| Experimental: MGD014 1.0 mcg/kg<br>a single 2-hour infusion | Biological: MGD014<br>* HIV-1 x CD3 bispecific DART molecule<br>|
| Experimental: MGD014 3.0 mcg/kg<br>a single 2-hour infusion | Biological: MGD014<br>* HIV-1 x CD3 bispecific DART molecule<br>|
| Experimental: MGD014 10.0 mcg/kg<br>a single 2-hour infusion | Biological: MGD014<br>* HIV-1 x CD3 bispecific DART molecule<br>|
| Experimental: MGD014 30.0 mcg/kg<br>a single 2-hour infusion | Biological: MGD014<br>* HIV-1 x CD3 bispecific DART molecule<br>|
| Experimental: MGD014 100.0 mcg/kg<br>a single 2-hour infusion | Biological: MGD014<br>* HIV-1 x CD3 bispecific DART molecule<br>|
| Experimental: MGD014 300.0 mcg/kg<br>a single 2-hour infusion | Biological: MGD014<br>* HIV-1 x CD3 bispecific DART molecule<br>|
| Experimental: MGD014 300.0 mcg/kg multiple doses<br>2-hour infusion every 2 weeks for 3 infusions | Biological: MGD014<br>* HIV-1 x CD3 bispecific DART molecule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emerging Adverse Events | Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit. | up to 77 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC Inf: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity of MGD014 | AUCinf, area under the concentration-time curve from the time of dose extrapolated to time infinity and reflects total drug exposure | Study Day 0 to 42 | 
| Cmax: Maximum Plasma Concentration | Cmax is the maximum (or peak) serum concentration of a drug in the body after the drug has been administered | Study Day 0 | 
| Tmax: Time to Maximum Concentration | Tmax is the time it takes a drug to reach the maximum concentration | Study Day 0 | 
| Ctrough: Trough Level Concentration | a trough level or trough concentration (Ctrough) is the concentration reached by a drug immediately before the next dose is administered, | Study Day 14 | 
| Clearance | Total body clearance of the drug from plasma of MGD014 | Study Day 0 to 42 | 
| Vz: Terminal Phase Volume of Distribution of MGD014 | The ratio of the total quantity of drug in the body to drug plasma concentration during the elimination | Study Day 1, 2, 7, 14, 21, 28, and 42 (single infusion) and Study Day 1, 3, 14, 28, 42, and 77 (multiple infusions) | 
| Terminal Half Life of MGD014 | The half-life is the amount of time required for 50% of the drug to be removed from the body | Study Day 0 to Study Day 42 | 
| Number of Participants That Developed Antidrug Antibodies to MGD014 | Number of participants with antidrug antibodies to MGD014 | Study Day 1, 14, 28 and 42 (single infusion) and Study Day 1, 14, 28 and 77 (multiple infusions) | 
| Number of Participants With Increased Cytokine Levels | Number of participants with increased cytokine levels from baseline after MGD014 administration. This safety measure compares serum cytokine levels obtained prior to dosing with levels obtained after dosing. Increased cytokines can be a measure of T-cell activation in response to MGD014 binding. Cytokines analyzed included interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)2, IL-5, IL-6, and IL-10. | Study Day 1, 2 and 7 (single infusion) and Study Day 1, 3, 14 and 28 (multiple infusions) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Latent HIV-1 infection, HIV therapy, antibody-based therapy