MGD014 in HIV-Infected Individuals on Suppressive Antiretroviral Therapy

NCT ID: NCT03570918

Last Updated: 2022-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-25
• Study Completion Date: 2021-09-28

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.

Conditions

HIV-1-infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MGD014 0.1 micrograms/kilogram (mcg/kg)

a single 2-hour infusion

Group Type: EXPERIMENTAL

MGD014

Intervention Type: BIOLOGICAL

HIV-1 x CD3 bispecific DART molecule

MGD014 0.3 mcg/kg

a single 2-hour infusion

Group Type: EXPERIMENTAL

MGD014

Intervention Type: BIOLOGICAL

HIV-1 x CD3 bispecific DART molecule

MGD014 1.0 mcg/kg

a single 2-hour infusion

Group Type: EXPERIMENTAL

MGD014

Intervention Type: BIOLOGICAL

HIV-1 x CD3 bispecific DART molecule

MGD014 3.0 mcg/kg

a single 2-hour infusion

Group Type: EXPERIMENTAL

MGD014

Intervention Type: BIOLOGICAL

HIV-1 x CD3 bispecific DART molecule

MGD014 10.0 mcg/kg

a single 2-hour infusion

Group Type: EXPERIMENTAL

MGD014

Intervention Type: BIOLOGICAL

HIV-1 x CD3 bispecific DART molecule

MGD014 30.0 mcg/kg

a single 2-hour infusion

Group Type: EXPERIMENTAL

MGD014

Intervention Type: BIOLOGICAL

HIV-1 x CD3 bispecific DART molecule

MGD014 100.0 mcg/kg

a single 2-hour infusion

Group Type: EXPERIMENTAL

MGD014

Intervention Type: BIOLOGICAL

HIV-1 x CD3 bispecific DART molecule

MGD014 300.0 mcg/kg

a single 2-hour infusion

Group Type: EXPERIMENTAL

MGD014

Intervention Type: BIOLOGICAL

HIV-1 x CD3 bispecific DART molecule

MGD014 300.0 mcg/kg multiple doses

2-hour infusion every 2 weeks for 3 infusions

Group Type: EXPERIMENTAL

MGD014

Intervention Type: BIOLOGICAL

HIV-1 x CD3 bispecific DART molecule

Interventions

MGD014

HIV-1 x CD3 bispecific DART molecule

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

MacroGenics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chief Medical Officer

Role: STUDY_DIRECTOR

MacroGenics

Locations

University of North Carolina Chapel Hill

Chapel Hill, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

272201500032C-2-0-1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CP-MGD014-01

Identifier Type: -

Identifier Source: org_study_id