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MGD014 in HIV-Infected Individuals on Suppressive Antiretroviral Therapy

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ClinicalTrials.gov Identifier: NCT03570918
Recruitment Status : Recruiting
First Posted : June 27, 2018
Last Update Posted : October 17, 2018
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
MacroGenics

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Intervention Model: Single Group 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
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: MGD014
HIV-1 x CD3 bispecific DART molecule
Biological: MGD014
HIV-1 x CD3 bispecific DART molecule




Primary Outcome Measures :
  1. Incidence of Treatment-Emerging Adverse Events [ Time Frame: 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 :
  1. AUC [ Time Frame: 24 months ]
    Area Under the Plasma Concentration versus Time Curve of MGD014

  2. Cmax [ Time Frame: 24 months ]
    Maximum Plasma Concentration of MGD014

  3. Tmax [ Time Frame: 24 months ]
    Time to maximal concentration of MGD014

  4. Ctrough [ Time Frame: 24 months ]
    Trough plasma concentration of MGD014

  5. CL [ Time Frame: 24 months ]
    Total body clearance of the drug from plasma of MGD014

  6. Vss [ Time Frame: 24 months ]
    Apparent volume of distribution at steady state of MGD014

  7. T1/2 [ Time Frame: 24 months ]
    Terminal half life of MGD014

  8. ADA [ Time Frame: 24 months ]
    Percent of participants with anti-drug antibody to MGD014

  9. Cytokines [ Time Frame: 24 months ]
    Assessment of serum cytokine levels following MGD014 administration

  10. Change in HIV-1 infection markers [ Time Frame: 24 months ]
    Frequency of resting CD4 T-cell infection and levels of plasma HIV-1 RNA



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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.
  • Karnofsky performance status > 70.
  • 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 ≥ 6 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.
  • Weight > 115 kg or < 53 kg.
  • 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 within 5 years, seizure disorder within 2 years, organ/tissue transplant, autoimmune disease, unstable asthma, bleeding disorder.
  • 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 within 30 days of screening.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03570918


Contacts
Contact: Joann Kuruc, MSN, RN 919-966-8533 joann_kuruc@med.unc.edu
Contact: Julia Sung, MD 919-843-1550 julia_sung@med.unc.edu

Locations
United States, North Carolina
University of North Carolina Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Joann Kuruc, MSN, RN    919-966-8533    joann_kuruc@med.unc.edu   
Contact: Julia Sung, MD    919-843-1550    julia_sung@med.unc.edu   
Principal Investigator: Julia Sung, MD         
Sponsors and Collaborators
MacroGenics
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Director: Jon Wigginton, MD MacroGenics

Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT03570918     History of Changes
Other Study ID Numbers: CP-MGD014-01
272201500032C-2-0-1 ( U.S. NIH Grant/Contract )
First Posted: June 27, 2018    Key Record Dates
Last Update Posted: October 17, 2018
Last Verified: October 2018
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