Clinical trial NCT03570918: MGD014 in HIV-Infected Individuals on Suppressive Antiretroviral Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV-1-infection
Keywords: HIV, Latent HIV-1 infection, HIV therapy, antibody-based therapy
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2018-06-27
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Open-label dose-escalation study
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emerging Adverse Events
timeFrame: up to 77 days
Secondary outcomes:
measure: AUC Inf: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity of MGD014
timeFrame: Study Day 0 to 42
measure: Cmax: Maximum Plasma Concentration
timeFrame: Study Day 0
measure: Tmax: Time to Maximum Concentration
timeFrame: Study Day 0
measure: Ctrough: Trough Level Concentration
timeFrame: Study Day 14
measure: Clearance
timeFrame: Study Day 0 to 42
measure: Vz: Terminal Phase Volume of Distribution of MGD014
timeFrame: Study Day 1, 2, 7, 14, 21, 28, and 42 (single infusion) and Study Day 1, 3, 14, 28, 42, and 77 (multiple infusions)
measure: Terminal Half Life of MGD014
timeFrame: Study Day 0 to Study Day 42
measure: Number of Participants That Developed Antidrug Antibodies to MGD014
timeFrame: Study Day 1, 14, 28 and 42 (single infusion) and Study Day 1, 14, 28 and 77 (multiple infusions)
measure: Number of Participants With Increased Cytokine Levels
timeFrame: Study Day 1, 2 and 7 (single infusion) and Study Day 1, 3, 14 and 28 (multiple infusions)
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina Chapel Hill
state: North Carolina
Study officials:
affiliation: MacroGenics
name: Chief Medical Officer
role: STUDY_DIRECTOR
References: