MGD014 in HIV-Infected Individuals on Suppressive Antiretroviral Therapy
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MGD014 HIV-1 x CD3 bispecific DART molecule |
Biological: MGD014
HIV-1 x CD3 bispecific DART molecule
|
Outcome Measures
Primary Outcome Measures
- Incidence of Treatment-Emerging Adverse Events [24 months]
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.
Secondary Outcome Measures
- AUC [24 months]
Area Under the Plasma Concentration versus Time Curve of MGD014
- Cmax [24 months]
Maximum Plasma Concentration of MGD014
- Tmax [24 months]
Time to maximal concentration of MGD014
- Ctrough [24 months]
Trough plasma concentration of MGD014
- CL [24 months]
Total body clearance of the drug from plasma of MGD014
- Vss [24 months]
Apparent volume of distribution at steady state of MGD014
- T1/2 [24 months]
Terminal half life of MGD014
- ADA [24 months]
Percent of participants with anti-drug antibody to MGD014
- Cytokines [24 months]
Assessment of serum cytokine levels following MGD014 administration
- Change in HIV-1 infection markers [24 months]
Frequency of resting CD4 T-cell infection and levels of plasma HIV-1 RNA
Eligibility Criteria
Criteria
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.
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On a potent, stable, continuous ART regimen for ≥ 24 months prior to Screening.
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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.
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Adequate organ function based on acceptable laboratory parameters.
Exclusion Criteria:
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Women of childbearing potential defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or menopause.
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History or other evidence of severe illness, immunodeficiency other than HIV, or any other condition that would make the potential participant unsuitable for study.
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History or other evidence of any condition or process for which signs or symptoms could be confused with reactions to MGD014.
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History of any HIV immunotherapy or HIV vaccine except for MGD014 within 12 months prior to screening.
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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.
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Evidence of active viral, or antifungal treatment within 7 days prior to the initiation of study drug
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Active, asymptomatic, or suspected COVID-19/SARS-CoV-2 infection.
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Active, untreated syphilis.
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Use of blood products, cytokine therapy, growth-stimulating factors, cytotoxic chemotherapy or investigational therapy within 90 days.
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Current use of the antivirals maraviroc and/or enfuvirtide.
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Any vaccination with exception of flu vaccine within 30 days of screening.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of North Carolina Chapel Hill | Chapel Hill | North Carolina | United States | 27599 |
Sponsors and Collaborators
- MacroGenics
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Study Director: Chet Bohac, MD, MacroGenics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CP-MGD014-01
- 272201500032C-2-0-1