MGD014 in HIV-Infected Individuals on Suppressive Antiretroviral Therapy

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

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).

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Biological: MGD014

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 Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

9

Arms and Interventions

Participant Group / 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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: MacroGenics
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 25, 2018
• Primary Completion (ACTUAL): September 28, 2021
• Study Completion (ACTUAL): September 28, 2021

Study Registration Dates

• First Submitted: June 18, 2018
• First Submitted That Met QC Criteria: June 18, 2018
• First Posted (ACTUAL): June 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 2, 2022
• Last Update Submitted That Met QC Criteria: August 31, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: HIV, Latent HIV-1 infection, HIV therapy, antibody-based therapy
• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: CP-MGD014-01; 272201500032C-2-0-1 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No