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| ID | Type | Description | Link |
|---|---|---|---|
| 272201500032C-2-0-1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MGD014 0.1 micrograms/kilogram (mcg/kg) | Experimental | a single 2-hour infusion |
|
| MGD014 0.3 mcg/kg | Experimental | a single 2-hour infusion |
|
| MGD014 1.0 mcg/kg | Experimental | a single 2-hour infusion |
|
| MGD014 3.0 mcg/kg | Experimental | a single 2-hour infusion |
|
| MGD014 10.0 mcg/kg | Experimental | a single 2-hour infusion |
|
| MGD014 30.0 mcg/kg | Experimental | a single 2-hour infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MGD014 | Biological | HIV-1 x CD3 bispecific DART molecule |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | up to 77 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Study Day 0 to 42 |
| Cmax: Maximum Plasma Concentration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Chief Medical Officer | MacroGenics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of North Carolina Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
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Three participants who were treated in Period 1 (single dose) in the 10, 100, or 300 mcg/kg dose cohorts were also treated in Period 2 (multiple dose) in the 300 mcg/kg dose cohort.
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| ID | Title | Description |
|---|---|---|
| FG000 | MGD014 0.1 Micrograms/Kilogram (mcg/kg) | a single 2-hour infusion MGD014: HIV-1 x CD3 bispecific DART molecule |
| FG001 | MGD014 0.3 mcg/kg | a single 2-hour infusion MGD014: HIV-1 x CD3 bispecific DART molecule |
| FG002 | MGD014 1.0 mcg/kg | a single 2-hour infusion MGD014: HIV-1 x CD3 bispecific DART molecule |
| FG003 | MGD014 3.0 mcg/kg | a single 2-hour infusion MGD014: HIV-1 x CD3 bispecific DART molecule |
| FG004 | MGD014 10.0 mcg/kg | a single 2-hour infusion MGD014: HIV-1 x CD3 bispecific DART molecule |
| FG005 | MGD014 30.0 mcg/kg | a single 2-hour infusion MGD014: HIV-1 x CD3 bispecific DART molecule |
| FG006 | MGD014 100.0 mcg/kg | a single 2-hour infusion MGD014: HIV-1 x CD3 bispecific DART molecule |
| FG007 | MGD014 300.0 mcg/kg | a single 2-hour infusion MGD014: HIV-1 x CD3 bispecific DART molecule |
| FG008 | MGD014 300 mcg/kg Multiple Doses | 3 infusions given every 2 weeks over 4 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
| |||||||||||||
| Period 2 |
|
The 3 participants treated with multiple doses of MGD014 were also treated with single doses of MGD014 at 10, 100 and 300 mg, respectively.
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| ID | Title | Description |
|---|---|---|
| BG000 | MGD014 0.1 mcg/kg | Single infusion of MGD014 |
| BG001 | MGD014 0.3 mcg/kg | Single infusion of MGD014 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | The 3 participants treated with multiple doses of MGD014 were also treated with single doses of MGD014 at 10, 100 and 300 mg, respectively |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | up to 77 days |
|
up to 19 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MGD014 0.1 mcg/kg | Single infusion of MGD014 | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymph node pain | Blood and lymphatic system disorders | MedDRA 24.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | MacroGenics, Inc. | 301-251-5172 | info@Macrogenics.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 31, 2021 | Feb 7, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 17, 2021 | Feb 7, 2022 | SAP_001.pdf |
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Open-label dose-escalation study
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| MGD014 100.0 mcg/kg |
| Experimental |
a single 2-hour infusion |
|
| MGD014 300.0 mcg/kg | Experimental | a single 2-hour infusion |
|
| MGD014 300.0 mcg/kg multiple doses | Experimental | 2-hour infusion every 2 weeks for 3 infusions |
|
Cmax is the maximum (or peak) serum concentration of a drug in the body after the drug has been administered |
| Study Day 0 |
| Tmax: Time to Maximum Concentration | Tmax is the time it takes a drug to reach the maximum concentration | Study Day 0 |
| 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, | Study Day 14 |
| Clearance | Total body clearance of the drug from plasma of MGD014 | Study Day 0 to 42 |
| 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 | Study Day 1, 2, 7, 14, 21, 28, and 42 (single infusion) and Study Day 1, 3, 14, 28, 42, and 77 (multiple infusions) |
| 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 | Study Day 0 to Study Day 42 |
| Number of Participants That Developed Antidrug Antibodies to MGD014 | Number of participants with antidrug antibodies to MGD014 | Study Day 1, 14, 28 and 42 (single infusion) and Study Day 1, 14, 28 and 77 (multiple infusions) |
| 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. | Study Day 1, 2 and 7 (single infusion) and Study Day 1, 3, 14 and 28 (multiple infusions) |
| COMPLETED |
|
| NOT COMPLETED |
|
| BG002 |
| MGD014 1.0 mcg/kg |
Single infusion of MGD014 |
| BG003 | MGD014 3.0 mcg/kg | Single infusion of MGD014 |
| BG004 | MGD014 10.0 mcg/kg | Single infusion of MGD014 |
| BG005 | MGD014 30 mcg/kg | Single infusion of MGD014 |
| BG006 | MGD014 100 mcg/kg | Single infusion of MGD014 |
| BG007 | MGD014 300 mcg/kg | Single infusion of MGD014 |
| BG008 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
a single 2-hour infusion MGD014: HIV-1 x CD3 bispecific DART molecule |
| OG003 | MGD014 3.0 mcg/kg | a single 2-hour infusion MGD014: HIV-1 x CD3 bispecific DART molecule |
| OG004 | MGD014 10.0 mcg/kg | a single 2-hour infusion MGD014: HIV-1 x CD3 bispecific DART molecule |
| OG005 | MGD014 30.0 mcg/kg | a single 2-hour infusion MGD014: HIV-1 x CD3 bispecific DART molecule |
| OG006 | MGD014 100.0 mcg/kg | a single 2-hour infusion MGD014: HIV-1 x CD3 bispecific DART molecule |
| OG007 | MGD014 300.0 mcg/kg | a single 2-hour infusion MGD014: HIV-1 x CD3 bispecific DART molecule |
| OG008 | MGD014 300.0 mcg/kg Multiple Doses | 2-hour infusion every 2 weeks for 3 infusions MGD014: HIV-1 x CD3 bispecific DART molecule |
|
|
| Secondary | 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 | Posted | Mean | 95% Confidence Interval | mcg/L*hr | Study Day 0 to 42 |
|
|
|
| Secondary | Cmax: Maximum Plasma Concentration | Cmax is the maximum (or peak) serum concentration of a drug in the body after the drug has been administered | Posted | Mean | 95% Confidence Interval | mcg/L | Study Day 0 |
|
|
|
| Secondary | Tmax: Time to Maximum Concentration | Tmax is the time it takes a drug to reach the maximum concentration | Posted | Mean | 95% Confidence Interval | hours | Study Day 0 |
|
|
|
| Secondary | 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, | Mean trough concentration for the 300 mcg/kg dose is from the first MGD014 infusion (taken at Day 14) for participants (n=3) in Part 2 only. Trough concentration is not applicable for single-dose cohorts. | Posted | Mean | 95% Confidence Interval | mcg/L | Study Day 14 |
|
|
|
| Secondary | Clearance | Total body clearance of the drug from plasma of MGD014 | Posted | Mean | 95% Confidence Interval | L/hr | Study Day 0 to 42 |
|
|
|
| Secondary | 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 | Posted | Mean | 95% Confidence Interval | liters | Study Day 1, 2, 7, 14, 21, 28, and 42 (single infusion) and Study Day 1, 3, 14, 28, 42, and 77 (multiple infusions) |
|
|
|
| Secondary | 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 | Average terminal half-life did not include participants in Part 2 (n=3) due to a shortened PK schedule that did not support estimation of half-life | Posted | Mean | 95% Confidence Interval | hours | Study Day 0 to Study Day 42 |
|
|
|
| Secondary | Number of Participants That Developed Antidrug Antibodies to MGD014 | Number of participants with antidrug antibodies to MGD014 | Posted | Count of Participants | Participants | Study Day 1, 14, 28 and 42 (single infusion) and Study Day 1, 14, 28 and 77 (multiple infusions) |
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | Study Day 1, 2 and 7 (single infusion) and Study Day 1, 3, 14 and 28 (multiple infusions) |
|
|
|
| 1 |
| 0 |
| 1 |
| 1 |
| 1 |
| EG001 | MGD014 0.3 mcg/kg | Single infusion of MGD014 | 0 | 1 | 0 | 1 | 1 | 1 |
| EG002 | MGD014 1.0 mcg/kg | Single infusion of MGD014 | 0 | 4 | 0 | 4 | 4 | 4 |
| EG003 | MGD014 3.0 mcg/kg | Single infusion of MGD014 | 0 | 3 | 0 | 3 | 3 | 3 |
| EG004 | MGD014 10.0 mcg/kg | Single infusion of MGD014 | 0 | 3 | 0 | 3 | 2 | 3 |
| EG005 | MGD014 30 mcg/kg | Single infusion of MGD014 | 0 | 3 | 0 | 3 | 2 | 3 |
| EG006 | MGD014 100 mcg/kg | Single infusion of MGD014 | 0 | 3 | 0 | 3 | 2 | 3 |
| EG007 | MGD014 300 mcg/kg | Single infusion of MGD014 | 0 | 3 | 0 | 3 | 3 | 3 |
| EG008 | Multiple Dose MGD014 300 mcg/kg | Infusion every 2 weeks for 3 infusions. | 0 | 3 | 0 | 3 | 2 | 3 |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 24.0 | Systematic Assessment | swollen lymph nodes |
|
| Cerumen impaction | Ear and labyrinth disorders | MedDRA 24.0 | Systematic Assessment | earwax impaction |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Application site erythema | General disorders | MedDRA 24.0 | Systematic Assessment | Application site redness |
|
| Fatigue | General disorders | MedDRA 24.0 | Systematic Assessment |
|
| Vessel puncture site bruise | General disorders | MedDRA 24.0 | Systematic Assessment |
|
| Vessel puncture site pain | General disorders | MedDRA 24.0 | Systematic Assessment |
|
| Infusion site bruising | General disorders | MedDRA 24.0 | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA 24.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 24.0 | Systematic Assessment |
|
| Vessel puncture site haemorrhage | General disorders | MedDRA 24.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
|
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment | Insect bite |
|
| Eye contusion | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
|
| Injury | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
|
| Skin laceration | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA 24.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 24.0 | Systematic Assessment |
|
| Blood pressure increased | Investigations | MedDRA 24.0 | Systematic Assessment |
|
| Electrocardiogram abnormal | Investigations | MedDRA 24.0 | Systematic Assessment |
|
| Glomerular filtration rate decreased | Investigations | MedDRA 24.0 | Systematic Assessment | lab measurement of kidney function decreased |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment | Joint pain |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment | muscle pain |
|
| Headache | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Seizure | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
|
| Sensory disturbance | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Emotional distress | Psychiatric disorders | MedDRA 24.0 | Systematic Assessment |
|
| Abnormal dreams | Psychiatric disorders | MedDRA 24.0 | Systematic Assessment |
|
| Nightmare | Psychiatric disorders | MedDRA 24.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
| Papule | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 24.0 | Systematic Assessment |
|
| Peripheral coldness | Vascular disorders | MedDRA 24.0 | Systematic Assessment |
|
Not provided