A Study of MGD020 Alone or Combined With MGD014 in Persons With HIV-1 on Antiretroviral Therapy

NCT05261191 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: CP-MGD020-01272201500032C-P00008-9999-1
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 3

Brief Summary

Study CP-MGD020-01 is a phase 1, open-label, dose-escalation, and multi-dose expansion study of MGD020 as a single agent or in combination with MGD014 in persons with HIV-1 (PWH) on antiretroviral therapy (ART). The study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and pharmacodynamics (PD) of the study drugs. The study consists of 3 parts (Part 1A, Part 1B, and Part 2). The participant's standard of care ART regimen is continued throughout the study period. MGD020 is a bispecific DART® molecule that binds CD3 and gp41 subunit of HIV-1 envelope. MGD014 is a bispecific DART® molecule that binds CD3 and gp120 subunit of HIV-1 envelope. These DART molecules redirect CD3+ T lymphocytes to kill HIV-1-infected CD4+ T cells. Part 1A evaluates groups of participants given a single dose of MGD020. A 2-week safety period is observed prior to escalation to the next dose level. Dose escalation continues until either the maximum tolerated dose (MTD) or maximum administered dose (MAD) is determined. Part 1B begins after the end of Part 1A. Part 1B evaluates groups of participants given a single dose of the MGD020 MTD or MAD from Part 1A and a fixed dose of of MGD014. The first group will be treated with a single dose of MGD020, at a dose determined to be one dose lower than the single-agent MTD/MAD from Part 1A, and a single 300 mcg/kg dose of MGD014. Dose escalation proceeds until either the MTD or MAD is determined. Part 2 begins after the end of Part 1B. Part 2 is a multi-dose expansion group. Each participant will receive the MTD or MAD of MGD020 from Part 1B and a fixed dose of MGD014 from Part 1B, administered every 2 weeks (Q2W) for 3 combination doses over 4 weeks. Up to 6 participants may be enrolled in Part 2.

Conditions

Human Immunodeficiency Virus I Infection; Immunodeficiency Virus Type 1, Human; Human Immunodeficiency Virus Type 1

Outcome Measures

Primary Outcomes (3)

• Number and Types of Adverse Events (AEs), Including Serious Adverse Events (SAEs), and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 Alone in Part 1A

  Observation of side effects determines the highest safe dose for further study

  Throughout the study, up to 43 days

• Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 1B.

  Observation of side effects determines the highest safe dose for further study

  Throughout the study, up to 43 days

• Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 2.

  Observation of side effects determines the highest safe dose for further study

  Throughout the study, up to 81 days.

Secondary Outcomes (15)

• Mean Maximum Concentration of MGD020

  Throughout the study, up to 43 days for Parts 1A and 1B, and up to 78 days for Part 2

• Mean Maximum Concentration of MGD014

  Throughout the study, up to 43 days for Part 1B, and up to 78 days for Part 2

• Mean Time to Maximal Concentration of MGD020

  Throughout the study, up to 43 days for Parts 1A and 1B, and up to 78 days for Part 2

• Mean Time to Maximal Concentration of MGD014

  Throughout the study, up to 43 days for Part 1B, and up to 78 days for Part 2

• Mean Area Under the Concentration-time Curve (AUC) of MGD020

  Throughout the study, up to 43 days for Parts 1A and 1B, and up to 78 days for Part 2

Study Arms (9)

Part 1A: Dose level 1

EXPERIMENTAL

Single dose MGD020

Biological: MGD020

Part 1A: Dose level 2

EXPERIMENTAL

Single dose MGD020

Biological: MGD020

Part 1A: Dose level 3

EXPERIMENTAL

Single dose MGD020

Biological: MGD020

Part 1A: Dose level 4

EXPERIMENTAL

Single dose MGD020

Biological: MGD020

Part 1A: Dose level 5

EXPERIMENTAL

Single dose MGD020

Biological: MGD020

Part 1A: Dose level 6

EXPERIMENTAL

Single dose MGD020

Biological: MGD020

Part 1B: MTD/MAD -1 MGD020 and MGD014

EXPERIMENTAL

Single dose MGD020 and MGD014

Biological: MGD020; Biological: MGD014

Part 1B: MTD/MAD MGD020 and MGD014

EXPERIMENTAL

Single dose MGD020 and MGD014

Biological: MGD020; Biological: MGD014

Part 2: MGD020 and MGD014

EXPERIMENTAL

Multiple doses of MGD020 and MGD014

Biological: MGD020; Biological: MGD014

Interventions

MGD020 BIOLOGICAL

MGD020 is a bispecific DART molecule that binds CD3 and gp41 subunit of HIV-1 envelope.

Part 1A: Dose level 1; Part 1A: Dose level 2; Part 1A: Dose level 3; Part 1A: Dose level 4; Part 1A: Dose level 5; Part 1A: Dose level 6; Part 1B: MTD/MAD -1 MGD020 and MGD014; Part 1B: MTD/MAD MGD020 and MGD014; Part 2: MGD020 and MGD014

MGD014 BIOLOGICAL

MGD014 is a bispecific DART molecule that binds CD3 and gp120 subunit of HIV-1 envelope.

Part 1B: MTD/MAD -1 MGD020 and MGD014; Part 1B: MTD/MAD MGD020 and MGD014; Part 2: MGD020 and MGD014

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 18 years and ≤ 70 years of age and able to provide informed consent
• HIV-1 infection documented by rapid HIV test or HIV enzyme or chemiluminescence immunoassay and confirmed by a different second test.
• Plasma HIV-1 RNA viral load
• \< 50 copies/mL at 2 time points within 24 months prior to screening (1 time point within 12 months prior to screening), and
• \< 50 copies/mL at screening, and
• Not ≥ 50 copies/mL on 2 consecutive time points within 24 months nor \> 1000 copies/mL at any time within 6 months prior to screening
• On continuous antiretroviral therapy (ART) for at least 24 months prior to screening and must continue ART throughout the study.
• CD4 cell count \> 350 cells/mm3 at screening
• Acceptable laboratory values related to bone marrow, kidney and liver function.
• Individuals of childbearing potential must agree to use highly effective forms of contraception throughout the study through 6 months after the last dose of MGD014.

You may not qualify if:

• History of any HIV-1 vaccine or HIV-1 immunotherapy, except MGD014 or MGD020, within 6 months prior to screening.
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient.
• Active viral, bacterial, or systemic fungal infection requiring intravenous antibiotic, antiviral, or antifungal treatment within 7 days prior to the initiation of study drug.
• Active coronavirus disease 19 (COVID-19)/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
• Participation in another investigational clinical research study within 60 days prior to screening.
• History of virologic failure on an ART regimen containing FDA-approved HIV-1 entry inhibitors (maraviroc, enfuvirtide, and/or ibalizumab). Virologic failure is defined as a confirmed plasma HIV-1 RNA ≥ 150 copies/mL following assessment of drug adherence, repeat HIV-1 RNA testing with continued treatment, and/or resistance testing

Sponsors & Collaborators

• MacroGenics: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• National Institutes of Health (NIH): collaborator
• Department of Health and Human Services: collaborator

Study Sites (3)

Icahn School of Medicine at Mt. Sinai

New York, New York, 10029, United States

Location

UNC Hospital - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Case Western Reserve University Hospital

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: MacroGenics, Inc.

info@macrogenics.com

301-251-5172

Study Officials

• Pepi Pencheva, MD

  MacroGenics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2022
• First Posted: March 2, 2022
• Study Start: September 26, 2022
• Primary Completion: May 29, 2024
• Study Completion: May 29, 2024
• Last Updated: March 28, 2025
• Results First Posted: March 28, 2025

Record last verified: 2025-03

Locations

US (3)