MGD014 in HIV-Infected Individuals on Suppressive Antiretroviral Therapy

• ClinicalTrials.gov Identifier: NCT03570918
• Recruitment Status: Completed
• First Posted: June 27, 2018
• Results First Posted: September 2, 2022
• Last Update Posted: September 2, 2022
• Sponsor: MacroGenics
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): MacroGenics

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
HIV-1-infection	Biological: MGD014	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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Open-label dose-escalation study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study to Evaluate the Safety, Immunologic and Virologic Responses of MGD014 Therapy in HIV-Infected Individuals on Suppressive Antiretroviral Therapy
• Actual Study Start Date: September 25, 2018
• Actual Primary Completion Date: September 28, 2021
• Actual Study Completion Date: September 28, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment-Emerging Adverse Events [ Time Frame: up to 77 days ]
   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 :

1. AUC Inf: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity of MGD014 [ Time Frame: Study Day 0 to 42 ]
   AUCinf, area under the concentration-time curve from the time of dose extrapolated to time infinity and reflects total drug exposure
2. Cmax: Maximum Plasma Concentration [ Time Frame: Study Day 0 ]
   Cmax is the maximum (or peak) serum concentration of a drug in the body after the drug has been administered
3. Tmax: Time to Maximum Concentration [ Time Frame: Study Day 0 ]
   Tmax is the time it takes a drug to reach the maximum concentration
4. Ctrough: Trough Level Concentration [ Time Frame: Study Day 14 ]
   a trough level or trough concentration (Ctrough) is the concentration reached by a drug immediately before the next dose is administered,
5. Clearance [ Time Frame: Study Day 0 to 42 ]
   Total body clearance of the drug from plasma of MGD014
6. Vz: Terminal Phase Volume of Distribution of MGD014 [ Time Frame: Study Day 1, 2, 7, 14, 21, 28, and 42 (single infusion) and Study Day 1, 3, 14, 28, 42, and 77 (multiple infusions) ]
   The ratio of the total quantity of drug in the body to drug plasma concentration during the elimination
7. Terminal Half Life of MGD014 [ Time Frame: Study Day 0 to Study Day 42 ]
   The half-life is the amount of time required for 50% of the drug to be removed from the body
8. Number of Participants That Developed Antidrug Antibodies to MGD014 [ Time Frame: Study Day 1, 14, 28 and 42 (single infusion) and Study Day 1, 14, 28 and 77 (multiple infusions) ]
   Number of participants with antidrug antibodies to MGD014
9. Number of Participants With Increased Cytokine Levels [ Time Frame: Study Day 1, 2 and 7 (single infusion) and Study Day 1, 3, 14 and 28 (multiple infusions) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.
• 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.

Contacts and Locations

Locations

United States, North Carolina

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: Chief Medical Officer; MacroGenics

  Study Documents (Full-Text)

Documents provided by MacroGenics:

Study Protocol  [PDF] March 31, 2021

Statistical Analysis Plan  [PDF] March 17, 2021

More Information

• Responsible Party: MacroGenics
• ClinicalTrials.gov Identifier: NCT03570918
• Other Study ID Numbers: CP-MGD014-01; 272201500032C-2-0-1 ( U.S. NIH Grant/Contract )
• First Posted: June 27, 2018
• Results First Posted: September 2, 2022
• Last Update Posted: September 2, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by MacroGenics:

HIV, Latent HIV-1 infection, HIV therapy, antibody-based therapy

Additional relevant MeSH terms:

Infections