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

Primary Purpose

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

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

MGD020

MGD014

About this trial

This is an interventional treatment trial for Human Immunodeficiency Virus I Infection

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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 4 months after the last dose of MGD024.

Exclusion Criteria:

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

Sites / Locations

Icahn School of Medicine at Mt. SinaiRecruiting
UNC Hospital - Chapel HillRecruiting
Case Western Reserve University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Arm Label

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

Arm Description

Single dose MGD020

Single dose MGD020 and MGD014

Multiple doses of MGD020 and MGD014

Outcomes

Primary Outcome Measures

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

Number and types of adverse events (AEs), including serious adverse events (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

Number and types of adverse events (AEs), including serious adverse events (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

Secondary Outcome Measures

Maximum concentration of MGD020

The highest concentration of MGD020 at the end of the infusion

Maximum concentration of MDG014

The highest concentration of MGD014 at the end of the infusion

Time to maximal concentration of MGD020

The amount of time required to get maximum concentration of MGD020

Time to maximal concentration of MGD014

The amount of time required to get maximum concentration of MGD014

Area under the concentration-time curve (AUC) of MGD020

Total body exposure to MGD020

AUC of MGD014

Total body exposure to MGD014

Trough concentration of MGD020

The amount of MGD020 left after dosing

Trough concentration of MGD014

The amount of MGD014 left after dosing

Half-life of MGD020

The amount of time needed for the body to clear half of the dose of MGD020

Half-life of MGD014

The amount of time needed for the body to clear half of the dose of MGD021

Volume of Distribution at steady state of MGD020

This parameter measures how much of the drug remains in the bloodstream or is distributed to body tissues.

Volume of Distribution at steady state of MGD014

This parameter measures how much of the drug remains in the bloodstream or is distributed to body tissues.

Clearance of MGD020

Total body clearance of the drug from plasma of MGD020

Clearance of MGD014

Total body clearance of the drug from plasma of MGD014

Change from baseline in serum cytokine levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, and TNF-α

Anti-drug antibody formation to MGD020

Number of patients who develop antibodies against MDG020

Anti-drug antibody formation to MGD014

Number of patients who develop antibodies against MDG014

Full Information

NCT ID

NCT05261191

First Posted

February 18, 2022

Last Updated

August 30, 2023

Sponsor

MacroGenics

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services

1. Study Identification

Unique Protocol Identification Number

NCT05261191

Brief Title

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

Official Title

A Phase 1 Study of MGD020 as a Single Agent or in Combination With MGD014 in Persons With HIV-1 on Antiretroviral Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 26, 2022 (Actual)

Primary Completion Date

March 2024 (Anticipated)

Study Completion Date

March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

MacroGenics

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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 Part 1B. Part 2 is a multi-dose expansion group. Each participant will receive the MTD or MAD of MGD020 and 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Part 1A: Dose level 1

Arm Type

Experimental

Arm Description

Single dose MGD020

Arm Title

Part 1A: Dose level 2

Arm Type

Experimental

Arm Description

Single dose MGD020

Arm Title

Part 1A: Dose level 3

Arm Type

Experimental

Arm Description

Single dose MGD020

Arm Title

Part 1A: Dose level 4

Arm Type

Experimental

Arm Description

Single dose MGD020

Arm Title

Part 1A: Dose level 5

Arm Type

Experimental

Arm Description

Single dose MGD020

Arm Title

Part 1A: Dose level 6

Arm Type

Experimental

Arm Description

Single dose MGD020

Arm Title

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

Arm Type

Experimental

Arm Description

Single dose MGD020 and MGD014

Arm Title

Part 1B: MTD/MAD MGD020 and MGD014

Arm Type

Experimental

Arm Description

Single dose MGD020 and MGD014

Arm Title

Part 2: MGD020 and MGD014

Arm Type

Experimental

Arm Description

Multiple doses of MGD020 and MGD014

Intervention Type

Biological

Intervention Name(s)

MGD020

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

MGD014

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

Throughout the study, up to 43 days

Title

Number and types of adverse events (AEs), including serious adverse events (SAEs), and AEs leading to treatment discontinuation in participants receiving MGD020 and MGD014 in Part 1B.

Description

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

Time Frame

Throughout the study, up to 43 days

Title

Number and types of adverse events (AEs), including serious adverse events (SAEs), and AEs leading to treatment discontinuation in participants receiving MGD020 and MGD014 in Part 2.

Description

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

Time Frame

Throughout the study, up to 81 days.

Secondary Outcome Measure Information:

Title

Maximum concentration of MGD020

Description

The highest concentration of MGD020 at the end of the infusion

Time Frame

Study Day 1, 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 1, 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2

Title

Maximum concentration of MDG014

Description

The highest concentration of MGD014 at the end of the infusion

Time Frame

Study Day 1, 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 1, 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2

Title

Time to maximal concentration of MGD020

Description

The amount of time required to get maximum concentration of MGD020

Time Frame

Study Day 1, 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 1, 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2

Title

Time to maximal concentration of MGD014

Description

The amount of time required to get maximum concentration of MGD014

Time Frame

Study Day 1, 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 1, 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2

Title

Area under the concentration-time curve (AUC) of MGD020

Description

Total body exposure to MGD020

Time Frame

Study Day 1, 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 1, 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2

Title

AUC of MGD014

Description

Total body exposure to MGD014

Time Frame

Study Day 1, 2, 3, 8, 15, 29, and 43 for Parts 1A and 1B. Study Day 1, 2, 3, 8, 15, 29, 43, 50, 64, and 78 for Part 2

Title

Trough concentration of MGD020

Description

The amount of MGD020 left after dosing

Time Frame