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CompletedNCT03570918Updated Sep 2, 2022Results posted

MGD014 in HIV-Infected Individuals on Suppressive Antiretroviral Therapy

A Phase 1 interventional study of MGD014 in HIV-1-infection, sponsored by MacroGenics. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2022-09-02.

Sponsored by MacroGenics · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
21
Allocation
Non-randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • HIV-1-infection

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Keywords

  • HIV, Latent HIV-1 infection, HIV therapy, antibody-based therapy
03

In context

Infections

6,687 studies on the registry are indexed under Infections; 807 are open to participants now.

This study's enrollment of 21 is below the median of 120 across 4,200 interventional studies indexed under Infections.

Browse Infections studies →

Lead sponsor

MacroGenics is the lead sponsor of 42 studies on the registry; 4 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 11 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
21 participants (actual)

Study arms

  • Experimental
    MGD014 0.1 micrograms/kilogram (mcg/kg)

    a single 2-hour infusion

    Biological: MGD014

  • Experimental
    MGD014 0.3 mcg/kg

    a single 2-hour infusion

    Biological: MGD014

  • Experimental
    MGD014 1.0 mcg/kg

    a single 2-hour infusion

    Biological: MGD014

  • Experimental
    MGD014 3.0 mcg/kg

    a single 2-hour infusion

    Biological: MGD014

  • Experimental
    MGD014 10.0 mcg/kg

    a single 2-hour infusion

    Biological: MGD014

  • Experimental
    MGD014 30.0 mcg/kg

    a single 2-hour infusion

    Biological: MGD014

  • Experimental
    MGD014 100.0 mcg/kg

    a single 2-hour infusion

    Biological: MGD014

  • Experimental
    MGD014 300.0 mcg/kg

    a single 2-hour infusion

    Biological: MGD014

  • Experimental
    MGD014 300.0 mcg/kg multiple doses

    2-hour infusion every 2 weeks for 3 infusions

    Biological: MGD014

Interventions

  • BiologicalMGD014

    HIV-1 x CD3 bispecific DART molecule

06

What researchers measure

Primary outcomes

  1. Number of Participants With Treatment-Emerging Adverse Events

    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.

    Time frame: up to 77 days

Secondary outcomes

  1. AUC Inf: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity of MGD014

    AUCinf, area under the concentration-time curve from the time of dose extrapolated to time infinity and reflects total drug exposure

    Time frame: Study Day 0 to 42

  2. Cmax: Maximum Plasma Concentration

    Cmax is the maximum (or peak) serum concentration of a drug in the body after the drug has been administered

    Time frame: Study Day 0

  3. Tmax: Time to Maximum Concentration

    Tmax is the time it takes a drug to reach the maximum concentration

    Time frame: Study Day 0

  4. Ctrough: Trough Level Concentration

    a trough level or trough concentration (Ctrough) is the concentration reached by a drug immediately before the next dose is administered,

    Time frame: Study Day 14

  5. Clearance

    Total body clearance of the drug from plasma of MGD014

    Time frame: Study Day 0 to 42

  6. Vz: Terminal Phase Volume of Distribution of MGD014

    The ratio of the total quantity of drug in the body to drug plasma concentration during the elimination

    Time frame: Study Day 1, 2, 7, 14, 21, 28, and 42 (single infusion) and Study Day 1, 3, 14, 28, 42, and 77 (multiple infusions)

  7. Terminal Half Life of MGD014

    The half-life is the amount of time required for 50% of the drug to be removed from the body

    Time frame: Study Day 0 to Study Day 42

  8. Number of Participants That Developed Antidrug Antibodies to MGD014

    Number of participants with antidrug antibodies to MGD014

    Time frame: Study Day 1, 14, 28 and 42 (single infusion) and Study Day 1, 14, 28 and 77 (multiple infusions)

  9. Number of Participants With Increased Cytokine Levels

    Number of participants with increased cytokine levels from baseline after MGD014 administration. This safety measure compares serum cytokine levels obtained prior to dosing with levels obtained after dosing. Increased cytokines can be a measure of T-cell activation in response to MGD014 binding. Cytokines analyzed included interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)2, IL-5, IL-6, and IL-10.

    Time frame: Study Day 1, 2 and 7 (single infusion) and Study Day 1, 3, 14 and 28 (multiple infusions)

07

Results

Posted Sep 2, 2022

Participant flow

Period 1
Participant flow — Period 1
MilestoneMGD014 0.1 Micrograms/Kilogram (mcg/kg)MGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30.0 mcg/kgMGD014 100.0 mcg/kgMGD014 300.0 mcg/kgMGD014 300 mcg/kg Multiple Doses
Started114333330
Completed114333330
Not completed000000000
Period 2
Participant flow — Period 2
MilestoneMGD014 0.1 Micrograms/Kilogram (mcg/kg)MGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30.0 mcg/kgMGD014 100.0 mcg/kgMGD014 300.0 mcg/kgMGD014 300 mcg/kg Multiple Doses
Started000000003
Completed000000003
Not completed000000000

Outcome measures

PrimaryNumber of Participants With Treatment-Emerging Adverse Events

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.

Time frame:
up to 77 days
Reported as:
Count of participants · Participants
Number of Participants With Treatment-Emerging Adverse Events
ParticipantsMGD014 0.1 Micrograms/Kilogram (mcg/kg)MGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30.0 mcg/kgMGD014 100.0 mcg/kgMGD014 300.0 mcg/kgMGD014 300.0 mcg/kg Multiple Doses
Number of Participants With Treatment-Emerging Adverse Events114322232
SecondaryAUC Inf: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity of MGD014

AUCinf, area under the concentration-time curve from the time of dose extrapolated to time infinity and reflects total drug exposure

Time frame:
Study Day 0 to 42
Reported as:
Mean · mcg/L*hr
AUC Inf: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity of MGD014
mcg/L*hrMGD014 0.1 mcg/kgMGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30.0 mcg/kgMGD014 100.0 mcg/kgMGD014 300.0 mcg/kg
AUC Inf: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity of MGD014134 (NA to NA)313 (NA to NA)2610 (1230 to 3990)6360 (5420 to 7300)22300 (20600 to 23900)50900 (43600 to 58200)170000 (129000 to 210000)497000 (445000 to 549000)
SecondaryCmax: Maximum Plasma Concentration

Cmax is the maximum (or peak) serum concentration of a drug in the body after the drug has been administered

Time frame:
Study Day 0
Reported as:
Mean · mcg/L
Cmax: Maximum Plasma Concentration
mcg/LMGD014 0.1 mcg/kgMGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30.0 mcg/kgMGD014 100.0 mcg/kgMGD014 300.0 mcg/kg
Cmax: Maximum Plasma Concentration2.9 (NA to NA)5.8 (NA to NA)24.5 (13.7 to 35.3)67.7 (50.3 to 85.1)181 (161 to 200)469 (390 to 548)1640 (1130 to 2160)5288.4 (4590 to 5870)
SecondaryTmax: Time to Maximum Concentration

Tmax is the time it takes a drug to reach the maximum concentration

Time frame:
Study Day 0
Reported as:
Mean · hours
Tmax: Time to Maximum Concentration
hoursMGD014 0.1 mcg/kgMGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30.0 mcg/kgMGD014 100.0 mcg/kgMGD014 300.0 mcg/kg
Tmax: Time to Maximum Concentration3.0 (NA to NA)1.9 (NA to NA)2.4 (1.6 to 3.1)2.0 (1.9 to 2.0)2.7 (1.9 to 3.4)1.9 (1.9 to 2.0)2.6 (1.9 to 3.4)2.5 (2.0 to 2.9)
SecondaryCtrough: Trough Level Concentration

a trough level or trough concentration (Ctrough) is the concentration reached by a drug immediately before the next dose is administered,

Time frame:
Study Day 14
Reported as:
Mean · mcg/L
Ctrough: Trough Level Concentration
mcg/LMGD014 0.1 mcg/kgMGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30.0 mcg/kgMGD014 100.0 mcg/kgMGD014 300.0 mcg/kg
Ctrough: Trough Level Concentration———————320 (252 to 338)
SecondaryClearance

Total body clearance of the drug from plasma of MGD014

Time frame:
Study Day 0 to 42
Reported as:
Mean · L/hr
Clearance
L/hrMGD014 0.1 mcg/kgMGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30.0 mcg/kgMGD014 100.0 mcg/kgMGD014 300.0 mcg/kg
Clearance0.04 (NA to NA)0.07 (NA to NA)0.03 (0.02 to 0.04)0.05 (0.04 to 0.05)0.04 (0.04 to 0.05)0.04 (0.04 to 0.05)0.05 (0.04 to 0.06)0.05 (0.05 to 0.06)
SecondaryVz: Terminal Phase Volume of Distribution of MGD014

The ratio of the total quantity of drug in the body to drug plasma concentration during the elimination

Time frame:
Study Day 1, 2, 7, 14, 21, 28, and 42 (single infusion) and Study Day 1, 3, 14, 28, 42, and 77 (multiple infusions)
Reported as:
Mean · liters
Vz: Terminal Phase Volume of Distribution of MGD014
litersMGD014 0.1 mcg/kgMGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30.0 mcg/kgMGD014 100.0 mcg/kgMGD014 300.0 mcg/kg
Vz: Terminal Phase Volume of Distribution of MGD0142.1 (NA to NA)4.1 (NA to NA)8.7 (6.2 to 11.2)19.7 (14.2 to 25.2)17.5 (16.9 to 18.2)17.4 (15.4 to 19.3)21.6 (16.9 to 26.2)15.8 (9.1 to 22.5)
SecondaryTerminal Half Life of MGD014

The half-life is the amount of time required for 50% of the drug to be removed from the body

Time frame:
Study Day 0 to Study Day 42
Reported as:
Mean · hours
Terminal Half Life of MGD014
hoursMGD014 0.1 mcg/kgMGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30.0 mcg/kgMGD014 100.0 mcg/kgMGD014 300.0 mcg/kg
Terminal Half Life of MGD01432.0 (NA to NA)38.6 (NA to NA)244 (136 to 351)300 (227 to 373)295 (266 to 323)282 (276 to 288)285 (269 to 300)295 (289 to 305)
SecondaryNumber of Participants That Developed Antidrug Antibodies to MGD014

Number of participants with antidrug antibodies to MGD014

Time frame:
Study Day 1, 14, 28 and 42 (single infusion) and Study Day 1, 14, 28 and 77 (multiple infusions)
Reported as:
Count of participants · Participants
Number of Participants That Developed Antidrug Antibodies to MGD014
ParticipantsMGD014 0.1 mcg/kgMGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30.0 mcg/kgMGD014 100.0 mcg/kgMGD014 300.0 mcg/kg
Number of Participants That Developed Antidrug Antibodies to MGD01400000002
SecondaryNumber of Participants With Increased Cytokine Levels

Number of participants with increased cytokine levels from baseline after MGD014 administration. This safety measure compares serum cytokine levels obtained prior to dosing with levels obtained after dosing. Increased cytokines can be a measure of T-cell activation in response to MGD014 binding. Cytokines analyzed included interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)2, IL-5, IL-6, and IL-10.

Time frame:
Study Day 1, 2 and 7 (single infusion) and Study Day 1, 3, 14 and 28 (multiple infusions)
Reported as:
Count of participants · Participants
Number of Participants With Increased Cytokine Levels
ParticipantsMGD014 0.1 mcg/kgMGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30.0 mcg/kgMGD014 100.0 mcg/kgMGD014 300.0 mcg/kg
Number of Participants With Increased Cytokine Levels00100000

Adverse events

Collected over up to 19 weeks. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
MGD014 0.1 mcg/kg0/1 (0%)0/1 (0%)1/1 (100%)
MGD014 0.3 mcg/kg0/1 (0%)0/1 (0%)1/1 (100%)
MGD014 1.0 mcg/kg0/4 (0%)0/4 (0%)4/4 (100%)
MGD014 3.0 mcg/kg0/3 (0%)0/3 (0%)3/3 (100%)
MGD014 10.0 mcg/kg0/3 (0%)0/3 (0%)2/3 (66.7%)
MGD014 30 mcg/kg0/3 (0%)0/3 (0%)2/3 (66.7%)
MGD014 100 mcg/kg0/3 (0%)0/3 (0%)2/3 (66.7%)
MGD014 300 mcg/kg0/3 (0%)0/3 (0%)3/3 (100%)
Multiple Dose MGD014 300 mcg/kg0/3 (0%)0/3 (0%)2/3 (66.7%)
Most frequent other events
Showing 10 of 48
Most frequent other events
EventMGD014 0.1 mcg/kgMGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30 mcg/kgMGD014 100 mcg/kgMGD014 300 mcg/kgMultiple Dose MGD014 300 mcg/kg
Vessel puncture site bruiseGeneral disorders0/11/11/40/30/30/30/30/31/3
Vessel puncture site painGeneral disorders0/11/12/40/30/30/30/30/30/3
Electrocardiogram QT prolongedInvestigations1/11/10/42/30/30/31/30/30/3
Infusion site bruisingGeneral disorders0/10/10/40/30/30/30/30/32/3
HeadacheNervous system disorders0/10/12/41/31/30/31/30/30/3
Lymph node painBlood and lymphatic system disorders0/10/10/40/31/30/30/30/30/3
LymphadenopathyBlood and lymphatic system disorders0/10/10/40/31/30/30/30/30/3
DiarrhoeaGastrointestinal disorders0/10/11/40/31/31/30/30/30/3
NauseaGastrointestinal disorders0/10/11/40/31/30/30/30/30/3
VomitingGastrointestinal disorders0/10/11/40/31/30/30/30/30/3

Baseline characteristics

The 3 participants treated with multiple doses of MGD014 were also treated with single doses of MGD014 at 10, 100 and 300 mg, respectively.

Age, Continuous
Age, Continuous(years)MGD014 0.1 mcg/kgMGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30 mcg/kgMGD014 100 mcg/kgMGD014 300 mcg/kgTotal
Period 1: Single Dose40.0 ± NA53.0 ± NA49.8 ± 9.1837.9 ± 5.5156.7 ± 7.0941.0 ± 10.8233.7 ± 5.8642.3 ± 17.1044.4 ± 11.00
Sex: Female, Male
Sex: Female, Male(Participants)MGD014 0.1 mcg/kgMGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30 mcg/kgMGD014 100 mcg/kgMGD014 300 mcg/kgTotal
Single dose — Female000000000
Single dose — Male1143333321
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)MGD014 0.1 mcg/kgMGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30 mcg/kgMGD014 100 mcg/kgMGD014 300 mcg/kgTotal
Hispanic or Latino001010002
Not Hispanic or Latino1133233319
Unknown or Not Reported000000000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)MGD014 0.1 mcg/kgMGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30 mcg/kgMGD014 100 mcg/kgMGD014 300 mcg/kgTotal
American Indian or Alaska Native000000000
Asian000000000
Native Hawaiian or Other Pacific Islander000000000
Black or African American100111127
White0132222113
More than one race000000000
Unknown or Not Reported001000001
Region of Enrollment
Region of Enrollment(participants)MGD014 0.1 mcg/kgMGD014 0.3 mcg/kgMGD014 1.0 mcg/kgMGD014 3.0 mcg/kgMGD014 10.0 mcg/kgMGD014 30 mcg/kgMGD014 100 mcg/kgMGD014 300 mcg/kgTotal
United States114333333
08

Study locations

1 site
  • University of North Carolina Chapel Hill
    Chapel Hill, North Carolina 27599, United States
09

References and documents

Study documents

  • Study protocol · Mar 31, 2021
  • Statistical analysis plan · Mar 17, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 2, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03570918
Lead sponsor
MacroGenics
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Responsible party
Sponsor
First posted
Jun 27, 2018
Start date
Sep 25, 2018
Primary completion
Sep 28, 2021
Completion
Sep 28, 2021
Results posted
Sep 2, 2022
Last update
Sep 2, 2022

Study contacts

Chief Medical Officer
study director · MacroGenics

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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