Human Immunodeficiency Virus I Infection, Human Immunodeficiency Virus Type 1, Immunodeficiency Virus Type 1, Human
Conditions
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.
Interventions
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health (NIH)
Department of Health and Human Services
MacroGenics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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 6 months after the last dose of MGD014.
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Throughout the study, up to 43 days | Observation of side effects determines the highest safe dose for further study |
| Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 1B. | Throughout the study, up to 43 days | Observation of side effects determines the highest safe dose for further study |
| Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 2. | Throughout the study, up to 81 days. | Observation of side effects determines the highest safe dose for further study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | The amount of time required to get maximum concentration of MGD014 |
| 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 | Total body exposure to MGD020 |
| Mean AUC of MGD014 | Throughout the study, up to 43 days for Parts 1B, and up to 78 days for Part 2 | Total body exposure to MGD014 |
| Mean Half-life of MGD020 | Throughout the study, up to 43 days for Parts 1A and 1B, and up to 78 days for Part 2 | The amount of time needed for the body to clear half of the dose of MGD020 |
| Mean Half-life of MGD014 | Throughout the study, up to 43 days for Parts 1B, and up to 78 days for Part 2 | The amount of time needed for the body to clear half of the dose of MGD014 |
| Mean Volume of Distribution at Steady State (Vss) of MGD020 | Throughout the study, up to 78 days for Part 2 | This parameter measures how much of the drug remains in the bloodstream or is distributed to body tissues. |
| 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 | The highest concentration of MGD020 at the end of the infusion |
| Mean Clearance of MGD020 | Throughout the study, up to 43 days for Parts 1A and 1B, and up to 78 days for Part 2 | Total body clearance of the drug from plasma of MGD020 |
| Mean Clearance of MGD014 | Throughout the study, up to 43 days for Parts 1B, and up to 78 days for Part 2 | Total body clearance of the drug from plasma of MGD014 |
| Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | Throughout the study, up to 43 days for Parts 1A and 1B, and up to 78 days for Part 2. | — |
| Anti-drug Antibody Formation to MGD020 | Throughout the study, up to 43 days for Parts 1A and 1B, and up to 78 days for Part 2 | Number of patients who develop antibodies against MDG020 |
| Anti-drug Antibody Formation to MGD014 | Throughout the study, up to 43 days for Parts 1B, and up to 78 days for Part 2 | Number of patients who develop antibodies against MDG014 |
| Mean Volume of Distribution at Steady State of MGD014 | Throughout the study, up to 78 days for Part 2 | This parameter measures how much of the drug remains in the bloodstream or is distributed to body tissues. |
| Mean Maximum Concentration of MGD014 | Throughout the study, up to 43 days for Part 1B, and up to 78 days for Part 2 | The highest concentration of MGD014 at the end of the infusion (Cmax). |
| 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 | The amount of time required to get maximum concentration of MGD020 |
Countries
United States
Participant flow
Pre-assignment details
Participants who completed treatment in Part 1A or Part 1B may be considered for treatment in a subsequent cohort in Part B2 or Part 2. Participants must continue to meet all eligibility criteria, not have experienced severe adverse events in Part 1, and do not have detectable antidrug antibodies against prior study treatment. Subsequent treatments assignments are not defined in advance when entering the study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1A: Cohort 1 Single dose: 1 mcg/kg MGD020 administered IV | 1 |
| Part 1A: Cohort 2 Single dose: 3 mcg/kg MGD020 administered IV | 1 |
| Part 1A: Cohort 3 Single dose: 10 mcg/kg MGD020 administered IV | 1 |
| Part 1A: Cohort 4 Single dose: 30 mcg/kg MGD020 administered IV | 3 |
| Part 1A: Cohort 5 Single dose: 100 mcg/kg MGD020 administered IV | 3 |
| Part 1A: Cohort 6 Single dose: 300 mcg/kg MGD020 administered IV | 6 |
| Part 1B: Cohort 1 Single dose: 100 mcg/kg MGD020 + 300 mcg/kg MGD014 administered IV. | 3 |
| Part 1B: Cohort 2 Single dose: 300 mcg/kg MGD020 + 300 mcg/kg MGD014 administered IV. | 3 |
| Part 2 Three doses: 300 mcg/kg MGD020 + 300 mcg/kg MGD014 administered IV once every 2 weeks for 4 weeks. | 3 |
| Total | 24 |
Baseline characteristics
| Characteristic | Part 1A: Cohort 1 | Part 1A: Cohort 2 | Part 1A: Cohort 3 | Part 1A: Cohort 4 | Part 1A: Cohort 5 | Part 1A: Cohort 6 | Total | Part 1B: Cohort 1 | Part 1B: Cohort 2 | Part 2 |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous Part 1A | 64.0 years | 57.0 years | 50.0 years | 58.0 years STANDARD_DEVIATION 3.46 | 52.0 years STANDARD_DEVIATION 14.73 | 53.2 years STANDARD_DEVIATION 10.89 | 54.7 years STANDARD_DEVIATION 9.39 | — | — | — |
| Age, Continuous Part 1B | — | — | — | — | — | — | 55.8 years STANDARD_DEVIATION 9.81 | 59.3 years STANDARD_DEVIATION 5.13 | 52.3 years STANDARD_DEVIATION 13.32 | — |
| Age, Continuous Part 2 | — | — | — | — | — | — | 57.0 years STANDARD_DEVIATION 3.46 | — | — | 57.0 years STANDARD_DEVIATION 3.46 |
| Race/Ethnicity, Customized Part 1A: American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — |
| Race/Ethnicity, Customized Part 1A : Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | — | — | — |
| Race/Ethnicity, Customized Part 1A Black or African American | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 8 Participants | — | — | — |
| Race/Ethnicity, Customized Part 1A: Hispanic | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | — | — | — |
| Race/Ethnicity, Customized Part 1A: Not Hispanic | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 4 Participants | 12 Participants | — | — | — |
| Race/Ethnicity, Customized Part 1A: Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — |
| Race/Ethnicity, Customized Part 1A: Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — |
| Race/Ethnicity, Customized Part 1A: White | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 6 Participants | — | — | — |
| Race/Ethnicity, Customized Part 1B: American Indian or Alaska Native | — | — | — | — | — | — | 1 Participants | 0 Participants | 1 Participants | — |
| Race/Ethnicity, Customized Part 1B: Asian | — | — | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | — |
| Race/Ethnicity, Customized Part 1B Black or African American | — | — | — | — | — | — | 2 Participants | 1 Participants | 1 Participants | — |
| Race/Ethnicity, Customized Part 1B: Hispanic | — | — | — | — | — | — | 3 Participants | 1 Participants | 2 Participants | — |
| Race/Ethnicity, Customized Part 1B: Not Hispanic | — | — | — | — | — | — | 3 Participants | 2 Participants | 1 Participants | — |
| Race/Ethnicity, Customized Part 1B: Not Reported | — | — | — | — | — | — | 1 Participants | 1 Participants | 0 Participants | — |
| Race/Ethnicity, Customized Part 1B: Other | — | — | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | — |
| Race/Ethnicity, Customized Part 1B: White | — | — | — | — | — | — | 2 Participants | 1 Participants | 1 Participants | — |
| Race/Ethnicity, Customized Part 2: American Indian or Alaska Native | — | — | — | — | — | — | 0 Participants | — | — | 0 Participants |
| Race/Ethnicity, Customized Part 2: Asian | — | — | — | — | — | — | 0 Participants | 0 Participants | — | 0 Participants |
| Race/Ethnicity, Customized Part 2: Black or African American | — | — | — | — | — | — | 2 Participants | — | — | 2 Participants |
| Race/Ethnicity, Customized Part 2: Hispanic | — | — | — | — | — | — | 2 Participants | — | — | 2 Participants |
| Race/Ethnicity, Customized Part 2: Not Hispanic | — | — | — | — | — | — | 1 Participants | — | — | 1 Participants |
| Race/Ethnicity, Customized Part 2: Not Reported | — | — | — | — | — | — | 0 Participants | — | — | 0 Participants |
| Race/Ethnicity, Customized Part 2: Other | — | — | — | — | — | — | 1 Participants | — | — | 1 Participants |
| Race/Ethnicity, Customized Part 2: White | — | — | — | — | — | — | 0 Participants | — | — | 0 Participants |
| Region of Enrollment United States | 1 participants | 1 participants | 1 participants | 3 participants | 3 participants | 6 participants | 3 participants | 3 participants | 3 participants | 3 participants |
| Sex: Female, Male Part 1A Female | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 5 Participants | — | — | — |
| Sex: Female, Male Part 1A Male | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 6 Participants | 10 Participants | — | — | — |
| Sex: Female, Male Part 1B Female | — | — | — | — | — | — | 1 Participants | 0 Participants | 1 Participants | — |
| Sex: Female, Male Part 1B Male | — | — | — | — | — | — | 5 Participants | 3 Participants | 2 Participants | — |
| Sex: Female, Male Part 2 Female | — | — | — | — | — | — | 1 Participants | — | — | 1 Participants |
| Sex: Female, Male Part 2 Male | — | — | — | — | — | — | 2 Participants | — | — | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 3 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 1 / 1 | 3 / 3 | 1 / 3 | 5 / 6 | 2 / 3 | 1 / 3 | 2 / 3 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 3 | 0 / 3 | 0 / 3 |
Outcome results
Primary
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
Time frame: Throughout the study, up to 43 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1A: Cohort 1 | 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 | Treatment-related severe adverse event | 0 participants with adverse events by type |
| Part 1A: Cohort 1 | 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 | Treatment-related Adverse Event | 0 participants with adverse events by type |
| Part 1A: Cohort 1 | 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 | Any Adverse Event | 1 participants with adverse events by type |
| Part 1A: Cohort 1 | 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 | Event leading to MGD020 withdrawal | 0 participants with adverse events by type |
| Part 1A: Cohort 1 | 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 | Severe adverse event | 0 participants with adverse events by type |
| Part 1A: Cohort 2 | 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 | Treatment-related Adverse Event | 1 participants with adverse events by type |
| Part 1A: Cohort 2 | 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 | Treatment-related severe adverse event | 0 participants with adverse events by type |
| Part 1A: Cohort 2 | 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 | Any Adverse Event | 1 participants with adverse events by type |
| Part 1A: Cohort 2 | 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 | Event leading to MGD020 withdrawal | 0 participants with adverse events by type |
| Part 1A: Cohort 2 | 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 | Severe adverse event | 0 participants with adverse events by type |
| Part 1A: Cohort 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 | Treatment-related Adverse Event | 1 participants with adverse events by type |
| Part 1A: Cohort 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 | Treatment-related severe adverse event | 0 participants with adverse events by type |
| Part 1A: Cohort 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 | Event leading to MGD020 withdrawal | 0 participants with adverse events by type |
| Part 1A: Cohort 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 | Severe adverse event | 0 participants with adverse events by type |
| Part 1A: Cohort 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 | Any Adverse Event | 1 participants with adverse events by type |
| Part 1A: Cohort 4 | 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 | Severe adverse event | 0 participants with adverse events by type |
| Part 1A: Cohort 4 | 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 | Any Adverse Event | 3 participants with adverse events by type |
| Part 1A: Cohort 4 | 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 | Treatment-related Adverse Event | 1 participants with adverse events by type |
| Part 1A: Cohort 4 | 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 | Treatment-related severe adverse event | 0 participants with adverse events by type |
| Part 1A: Cohort 4 | 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 | Event leading to MGD020 withdrawal | 0 participants with adverse events by type |
| Part 1A: Cohort 5 | 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 | Treatment-related severe adverse event | 0 participants with adverse events by type |
| Part 1A: Cohort 5 | 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 | Any Adverse Event | 1 participants with adverse events by type |
| Part 1A: Cohort 5 | 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 | Event leading to MGD020 withdrawal | 0 participants with adverse events by type |
| Part 1A: Cohort 5 | 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 | Treatment-related Adverse Event | 0 participants with adverse events by type |
| Part 1A: Cohort 5 | 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 | Severe adverse event | 0 participants with adverse events by type |
| Part 1A: Cohort 6 | 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 | Any Adverse Event | 5 participants with adverse events by type |
| Part 1A: Cohort 6 | 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 | Treatment-related severe adverse event | 0 participants with adverse events by type |
| Part 1A: Cohort 6 | 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 | Treatment-related Adverse Event | 2 participants with adverse events by type |
| Part 1A: Cohort 6 | 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 | Event leading to MGD020 withdrawal | 0 participants with adverse events by type |
| Part 1A: Cohort 6 | 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 | Severe adverse event | 0 participants with adverse events by type |
Primary
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
Time frame: Throughout the study, up to 43 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1A: Cohort 1 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 1B. | Any AE | 2 participants with AE by type |
| Part 1A: Cohort 1 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 1B. | Treatment-related AE | 2 participants with AE by type |
| Part 1A: Cohort 1 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 1B. | Severe AE | 1 participants with AE by type |
| Part 1A: Cohort 1 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 1B. | Severe treatment-related AE | 0 participants with AE by type |
| Part 1A: Cohort 1 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 1B. | Event leading to MGD020 withdrawal | 0 participants with AE by type |
| Part 1A: Cohort 1 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 1B. | Event leading to MGD014 withdrawal | 0 participants with AE by type |
| Part 1A: Cohort 2 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 1B. | Event leading to MGD020 withdrawal | 0 participants with AE by type |
| Part 1A: Cohort 2 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 1B. | Any AE | 1 participants with AE by type |
| Part 1A: Cohort 2 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 1B. | Severe treatment-related AE | 0 participants with AE by type |
| Part 1A: Cohort 2 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 1B. | Treatment-related AE | 0 participants with AE by type |
| Part 1A: Cohort 2 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 1B. | Event leading to MGD014 withdrawal | 0 participants with AE by type |
| Part 1A: Cohort 2 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 1B. | Severe AE | 0 participants with AE by type |
Primary
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
Time frame: Throughout the study, up to 81 days.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1A: Cohort 1 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 2. | Any AE | 2 participants with AE by type |
| Part 1A: Cohort 1 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 2. | Treatment-related AE | 0 participants with AE by type |
| Part 1A: Cohort 1 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 2. | Severe AE | 0 participants with AE by type |
| Part 1A: Cohort 1 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 2. | Severe treatment-related AE | 0 participants with AE by type |
| Part 1A: Cohort 1 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 2. | Event leading to MGD020 withdrawal | 0 participants with AE by type |
| Part 1A: Cohort 1 | Number and Types of AEs, Including SAEs, and AEs Leading to Treatment Discontinuation in Participants Receiving MGD020 and MGD014 in Part 2. | Event leading to MGD014 withdrawal | 0 participants with AE by type |
Secondary
Anti-drug Antibody Formation to MGD014
Number of patients who develop antibodies against MDG014
Time frame: Throughout the study, up to 43 days for Parts 1B, and up to 78 days for Part 2
Population: All participants who received at least 1 dose of MGD014. Participants in Part 1A did not receive MGD014.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1A: Cohort 1 | Anti-drug Antibody Formation to MGD014 | Negative before treatment, and negative after treatment | 3 Participants |
| Part 1A: Cohort 1 | Anti-drug Antibody Formation to MGD014 | Negative before treatment, and positive at least once after treatment | 0 Participants |
| Part 1A: Cohort 2 | Anti-drug Antibody Formation to MGD014 | Negative before treatment, and negative after treatment | 3 Participants |
| Part 1A: Cohort 2 | Anti-drug Antibody Formation to MGD014 | Negative before treatment, and positive at least once after treatment | 0 Participants |
| Part 1A: Cohort 3 | Anti-drug Antibody Formation to MGD014 | Negative before treatment, and positive at least once after treatment | 0 Participants |
| Part 1A: Cohort 3 | Anti-drug Antibody Formation to MGD014 | Negative before treatment, and negative after treatment | 3 Participants |
Secondary
Anti-drug Antibody Formation to MGD020
Number of patients who develop antibodies against MDG020
Time frame: Throughout the study, up to 43 days for Parts 1A and 1B, and up to 78 days for Part 2
Population: All participants who received at least one dose of assigned study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1A: Cohort 1 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and negative after treatment | 1 Participants |
| Part 1A: Cohort 1 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and positive at least once after treatment | 0 Participants |
| Part 1A: Cohort 1 | Anti-drug Antibody Formation to MGD020 | Positive before treatment and positive after treatment | 0 Participants |
| Part 1A: Cohort 2 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and negative after treatment | 0 Participants |
| Part 1A: Cohort 2 | Anti-drug Antibody Formation to MGD020 | Positive before treatment and positive after treatment | 1 Participants |
| Part 1A: Cohort 2 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and positive at least once after treatment | 0 Participants |
| Part 1A: Cohort 3 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and positive at least once after treatment | 0 Participants |
| Part 1A: Cohort 3 | Anti-drug Antibody Formation to MGD020 | Positive before treatment and positive after treatment | 0 Participants |
| Part 1A: Cohort 3 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and negative after treatment | 1 Participants |
| Part 1A: Cohort 4 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and positive at least once after treatment | 0 Participants |
| Part 1A: Cohort 4 | Anti-drug Antibody Formation to MGD020 | Positive before treatment and positive after treatment | 0 Participants |
| Part 1A: Cohort 4 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and negative after treatment | 3 Participants |
| Part 1A: Cohort 5 | Anti-drug Antibody Formation to MGD020 | Positive before treatment and positive after treatment | 0 Participants |
| Part 1A: Cohort 5 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and negative after treatment | 3 Participants |
| Part 1A: Cohort 5 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and positive at least once after treatment | 0 Participants |
| Part 1A: Cohort 6 | Anti-drug Antibody Formation to MGD020 | Positive before treatment and positive after treatment | 1 Participants |
| Part 1A: Cohort 6 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and negative after treatment | 4 Participants |
| Part 1A: Cohort 6 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and positive at least once after treatment | 1 Participants |
| Part 1B: Cohort 1 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and negative after treatment | 3 Participants |
| Part 1B: Cohort 1 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and positive at least once after treatment | 0 Participants |
| Part 1B: Cohort 1 | Anti-drug Antibody Formation to MGD020 | Positive before treatment and positive after treatment | 0 Participants |
| Part 1B: Cohort 2 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and negative after treatment | 3 Participants |
| Part 1B: Cohort 2 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and positive at least once after treatment | 0 Participants |
| Part 1B: Cohort 2 | Anti-drug Antibody Formation to MGD020 | Positive before treatment and positive after treatment | 0 Participants |
| Part 2 | Anti-drug Antibody Formation to MGD020 | Positive before treatment and positive after treatment | 0 Participants |
| Part 2 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and positive at least once after treatment | 0 Participants |
| Part 2 | Anti-drug Antibody Formation to MGD020 | Negative before treatment and negative after treatment | 3 Participants |
Secondary
Mean Area Under the Concentration-time Curve (AUC) of MGD020
Total body exposure to MGD020
Time frame: Throughout the study, up to 43 days for Parts 1A and 1B, and up to 78 days for Part 2
Population: All participants who received at least a single-dose of MGD020, and had at least 1 measurable concentration above the LLOQ. One participant in Part A, cohort 4 was excluded from the analysis due to no measurable concentration above the LLOQ. Mean AUC for Part 2 is after the first infusion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1A: Cohort 1 | Mean Area Under the Concentration-time Curve (AUC) of MGD020 | 5570 mcg*hour/liter |
| Part 1A: Cohort 2 | Mean Area Under the Concentration-time Curve (AUC) of MGD020 | 9280 mcg*hour/liter |
| Part 1A: Cohort 3 | Mean Area Under the Concentration-time Curve (AUC) of MGD020 | 29400 mcg*hour/liter |
| Part 1A: Cohort 4 | Mean Area Under the Concentration-time Curve (AUC) of MGD020 | 88900 mcg*hour/liter |
| Part 1A: Cohort 5 | Mean Area Under the Concentration-time Curve (AUC) of MGD020 | 283667 mcg*hour/liter |
| Part 1A: Cohort 6 | Mean Area Under the Concentration-time Curve (AUC) of MGD020 | 957833 mcg*hour/liter |
| Part 1B: Cohort 1 | Mean Area Under the Concentration-time Curve (AUC) of MGD020 | 365667 mcg*hour/liter |
| Part 1B: Cohort 2 | Mean Area Under the Concentration-time Curve (AUC) of MGD020 | 1088333 mcg*hour/liter |
| Part 2 | Mean Area Under the Concentration-time Curve (AUC) of MGD020 | 854333 mcg*hour/liter |
Secondary
Mean AUC of MGD014
Total body exposure to MGD014
Time frame: Throughout the study, up to 43 days for Parts 1B, and up to 78 days for Part 2
Population: All participants who received at least a single-dose of MGD014, and had at least 1 measurable concentration above the LLOQ. Mean AUC for Part 2 is after the first infusion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1A: Cohort 1 | Mean AUC of MGD014 | 572333 mcg*hour/liter |
| Part 1A: Cohort 2 | Mean AUC of MGD014 | 631000 mcg*hour/liter |
| Part 1A: Cohort 3 | Mean AUC of MGD014 | 581333 mcg*hour/liter |
Secondary
Mean Clearance of MGD014
Total body clearance of the drug from plasma of MGD014
Time frame: Throughout the study, up to 43 days for Parts 1B, and up to 78 days for Part 2
Population: All participants who received at least one dose of MGD014. Clearance for Part 2 is reported after the third dose of MGD014.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1A: Cohort 1 | Mean Clearance of MGD014 | 0.02 liters |
| Part 1A: Cohort 2 | Mean Clearance of MGD014 | 0.04 liters |
| Part 1A: Cohort 3 | Mean Clearance of MGD014 | 0.02 liters |
Secondary
Mean Clearance of MGD020
Total body clearance of the drug from plasma of MGD020
Time frame: Throughout the study, up to 43 days for Parts 1A and 1B, and up to 78 days for Part 2
Population: All participants who received at least a single-dose of MGD020, and had at least 1 measurable concentration above the LLOQ. One participant in Part A, cohort 4 was excluded from analysis due to no measurable concentration above the LLOQ.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1A: Cohort 1 | Mean Clearance of MGD020 | 0.02 liters |
| Part 1A: Cohort 2 | Mean Clearance of MGD020 | 0.03 liters |
| Part 1A: Cohort 3 | Mean Clearance of MGD020 | 0.04 liters |
| Part 1A: Cohort 4 | Mean Clearance of MGD020 | 0.03 liters |
| Part 1A: Cohort 5 | Mean Clearance of MGD020 | 0.034 liters |
| Part 1A: Cohort 6 | Mean Clearance of MGD020 | 0.03 liters |
| Part 1B: Cohort 1 | Mean Clearance of MGD020 | 0.03 liters |
| Part 1B: Cohort 2 | Mean Clearance of MGD020 | 0.02 liters |
| Part 2 | Mean Clearance of MGD020 | 0.012 liters |
Secondary
Mean Half-life of MGD014
The amount of time needed for the body to clear half of the dose of MGD014
Time frame: Throughout the study, up to 43 days for Parts 1B, and up to 78 days for Part 2
Population: All participants who received at least a single-dose of MGD014, and had at least 1 measurable concentration above the LLOQ. Mean AUC for Part 2 is after the third infusion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1A: Cohort 1 | Mean Half-life of MGD014 | 273 hours |
| Part 1A: Cohort 2 | Mean Half-life of MGD014 | 296 hours |
| Part 1A: Cohort 3 | Mean Half-life of MGD014 | 339 hours |
Secondary
Mean Half-life of MGD020
The amount of time needed for the body to clear half of the dose of MGD020
Time frame: Throughout the study, up to 43 days for Parts 1A and 1B, and up to 78 days for Part 2
Population: All participants who received at least a single-dose of MGD020, and had at least 1 measurable concentration above the LLOQ. One participant in Part A, cohort 4 was excluded from the analysis due to no measurable concentration above the LLOQ.. Mean half-life for Part 2 is after the third infusion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1A: Cohort 1 | Mean Half-life of MGD020 | 202 hours |
| Part 1A: Cohort 2 | Mean Half-life of MGD020 | 462 hours |
| Part 1A: Cohort 3 | Mean Half-life of MGD020 | 209 hours |
| Part 1A: Cohort 4 | Mean Half-life of MGD020 | 309 hours |
| Part 1A: Cohort 5 | Mean Half-life of MGD020 | 323 hours |
| Part 1A: Cohort 6 | Mean Half-life of MGD020 | 221 hours |
| Part 1B: Cohort 1 | Mean Half-life of MGD020 | 353 hours |
| Part 1B: Cohort 2 | Mean Half-life of MGD020 | 361 hours |
| Part 2 | Mean Half-life of MGD020 | 452 hours |
Secondary
Mean Maximum Concentration of MGD014
The highest concentration of MGD014 at the end of the infusion (Cmax).
Time frame: Throughout the study, up to 43 days for Part 1B, and up to 78 days for Part 2
Population: All participants who received at least a single-dose of MGD014, and had at least 1 measurable concentration above the LLOQ. Mean Cmax for Part 2 is after the third infusion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1A: Cohort 1 | Mean Maximum Concentration of MGD014 | 6070 mcg/liter |
| Part 1A: Cohort 2 | Mean Maximum Concentration of MGD014 | 6297 mcg/liter |
| Part 1A: Cohort 3 | Mean Maximum Concentration of MGD014 | 7043 mcg/liter |
Secondary
Mean Maximum Concentration of MGD020
The highest concentration of MGD020 at the end of the infusion
Time frame: Throughout the study, up to 43 days for Parts 1A and 1B, and up to 78 days for Part 2
Population: All participants who received ay least a single-dose of MGD020, and had at least 1 measurable concentration above the lower limit of quantification (LLOQ). One participant in Part A, cohort 4 was excluded from the analysis due to no measurable concentration above the LLOQ. Mean Cmax for Part 2 is after the third infusion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1A: Cohort 1 | Mean Maximum Concentration of MGD020 | 54.2 mcg/liter |
| Part 1A: Cohort 2 | Mean Maximum Concentration of MGD020 | 45.8 mcg/liter |
| Part 1A: Cohort 3 | Mean Maximum Concentration of MGD020 | 185.0 mcg/liter |
| Part 1A: Cohort 4 | Mean Maximum Concentration of MGD020 | 540.5 mcg/liter |
| Part 1A: Cohort 5 | Mean Maximum Concentration of MGD020 | 2000 mcg/liter |
| Part 1A: Cohort 6 | Mean Maximum Concentration of MGD020 | 6415 mcg/liter |
| Part 1B: Cohort 1 | Mean Maximum Concentration of MGD020 | 3410 mcg/liter |
| Part 1B: Cohort 2 | Mean Maximum Concentration of MGD020 | 6947 mcg/liter |
| Part 2 | Mean Maximum Concentration of MGD020 | 8593 mcg/liter |
Secondary
Mean Time to Maximal Concentration of MGD014
The amount of time required to get maximum concentration of MGD014
Time frame: Throughout the study, up to 43 days for Part 1B, and up to 78 days for Part 2
Population: All participants who received at least a single-dose of MGD014, and had at least 1 measurable concentration above the LLOQ. Mean Tmax for Part 2 is after the first infusion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1A: Cohort 1 | Mean Time to Maximal Concentration of MGD014 | 2.7 hours |
| Part 1A: Cohort 2 | Mean Time to Maximal Concentration of MGD014 | 1.7 hours |
| Part 1A: Cohort 3 | Mean Time to Maximal Concentration of MGD014 | 1.3 hours |
Secondary
Mean Time to Maximal Concentration of MGD020
The amount of time required to get maximum concentration of MGD020
Time frame: Throughout the study, up to 43 days for Parts 1A and 1B, and up to 78 days for Part 2
Population: All participants who received at least a single-dose of MGD020, and had at least 1 measurable concentration above the LLOQ. One participant in Part A, cohort 4 was excluded from the analysis due to no measurable concentration above the LLOQ.. Mean Tmax for Part 2 is after the first infusion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1A: Cohort 1 | Mean Time to Maximal Concentration of MGD020 | 1.4 hours |
| Part 1A: Cohort 2 | Mean Time to Maximal Concentration of MGD020 | 2.1 hours |
| Part 1A: Cohort 3 | Mean Time to Maximal Concentration of MGD020 | 2.1 hours |
| Part 1A: Cohort 4 | Mean Time to Maximal Concentration of MGD020 | 1.6 hours |
| Part 1A: Cohort 5 | Mean Time to Maximal Concentration of MGD020 | 1.4 hours |
| Part 1A: Cohort 6 | Mean Time to Maximal Concentration of MGD020 | 2.1 hours |
| Part 1B: Cohort 1 | Mean Time to Maximal Concentration of MGD020 | 3.8 hours |
| Part 1B: Cohort 2 | Mean Time to Maximal Concentration of MGD020 | 1.2 hours |
| Part 2 | Mean Time to Maximal Concentration of MGD020 | 1.0 hours |
Secondary
Mean 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.
Time frame: Throughout the study, up to 78 days for Part 2
Population: Only participants who received at least 3 doses of MGD014 can be evaluated for Vss. All other cohorts receive only 1 dose, so Vss cannot be calculated in Parts 1A and 1B. Vss is reported only in Part 2 after the third dose of MGD014.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 2 | Mean Volume of Distribution at Steady State of MGD014 | 3.5 liters |
Secondary
Mean Volume of Distribution at Steady State (Vss) of MGD020
This parameter measures how much of the drug remains in the bloodstream or is distributed to body tissues.
Time frame: Throughout the study, up to 78 days for Part 2
Population: Only participants who received at least 3 doses of MGD020 can be evaluated for Vss. All other cohorts receive only 1 dose, so Vss cannot be calculated in Parts 1A and 1B. Vss is reported only for Part 2 after the third dose of MGD020.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 2 | Mean Volume of Distribution at Steady State (Vss) of MGD020 | 4.0 liters |
Secondary
Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α
Time frame: Throughout the study, up to 43 days for Parts 1A and 1B, and up to 78 days for Part 2.
Population: All participants who received at least one dose of assigned study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1A: Cohort 1 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | No elevation of serum cytokine levels | 1 Participants |
| Part 1A: Cohort 1 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | Elevation of at least 1 serum cytokine level. | 0 Participants |
| Part 1A: Cohort 2 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | No elevation of serum cytokine levels | 1 Participants |
| Part 1A: Cohort 2 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | Elevation of at least 1 serum cytokine level. | 0 Participants |
| Part 1A: Cohort 3 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | No elevation of serum cytokine levels | 1 Participants |
| Part 1A: Cohort 3 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | Elevation of at least 1 serum cytokine level. | 0 Participants |
| Part 1A: Cohort 4 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | No elevation of serum cytokine levels | 3 Participants |
| Part 1A: Cohort 4 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | Elevation of at least 1 serum cytokine level. | 0 Participants |
| Part 1A: Cohort 5 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | No elevation of serum cytokine levels | 3 Participants |
| Part 1A: Cohort 5 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | Elevation of at least 1 serum cytokine level. | 0 Participants |
| Part 1A: Cohort 6 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | Elevation of at least 1 serum cytokine level. | 3 Participants |
| Part 1A: Cohort 6 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | No elevation of serum cytokine levels | 3 Participants |
| Part 1B: Cohort 1 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | Elevation of at least 1 serum cytokine level. | 2 Participants |
| Part 1B: Cohort 1 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | No elevation of serum cytokine levels | 1 Participants |
| Part 1B: Cohort 2 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | No elevation of serum cytokine levels | 1 Participants |
| Part 1B: Cohort 2 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | Elevation of at least 1 serum cytokine level. | 2 Participants |
| Part 2 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | No elevation of serum cytokine levels | 0 Participants |
| Part 2 | Number of Participants With Elevations in Serum Cytokine Levels of IFN-γ, IL-2, IL-5, IL-6, IL-10, or TNF-α | Elevation of at least 1 serum cytokine level. | 3 Participants |