Healthy Subjects
Conditions
Keywords
Healthy subjects, MEDI7814, FTiH
Brief summary
This is a Phase 1 study to evaluate the safety and tolerability of single ascending intravenous doses of MEDI7814 in healthy adult subjects.
Detailed description
This is a Phase 1, randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of single ascending intravenous doses of MEDI7814 in healthy adult male subjects and female subjects of non-childbearing potential.
Interventions
OTHERPlacebo
A single dose of placebo matched to MEDI7814 intravenous infusion over at least 60 minutes on Day 1.
BIOLOGICALMEDI7814, 1 MG/KG
A single dose of MEDI7814, 1 mg/kg intravenous infusion over at least 60 minutes on Day 1.
BIOLOGICALMEDI7814, 3 MG/KG
A single dose of MEDI7814, 3 mg/kg intravenous infusion over at least 60 minutes on Day 1.
BIOLOGICALMEDI7814, 10 MG/KG
A single dose of MEDI7814, 10 mg/kg intravenous infusion over at least 60 minutes on Day 1.
BIOLOGICALMEDI7814, 20 MG/KG
A single dose of MEDI7814, 20 mg/kg intravenous infusion over at least 60 minutes on Day 1.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 18 years up to and including 49 years at the time of first dose of investigational product * Healthy by medical history, physical examination, and laboratory studies * Body weight 50-125 kilogram (kg); body mass index 19.0-32.0 kilogram per square meter (kg/m\^2) (inclusive) * Females must be of non-childbearing potential.
Exclusion criteria
* Any acute illness within 30 days of screening * Concurrent enrollment in another clinical trial * The subject has a positive drug/alcohol screen at screening or Day -1 * Pregnancy * Current cigarette smokers * History of cancer other than non-melanoma skin cancer or in situ carcinoma of the cervix treated with apparent success * Use of immunosuppressive medications * Subjects who have an unresolved infection with any Neisseria species * Subjects who have had their spleen removed for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Day 1 to Day 106 | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to Day 106 that were absent before treatment or that worsened relative to pretreatment state. AEs included SAEs as well as non-serious AEs which occurred during the trial. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameters of MEDI7814 | Predose, end of infusion, 2, 6, 12 hours post-end of infusion on Day 1; Day 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 106 | Individual MEDI7814 plasma concentration data and descriptive statistics of the PK parameters were to be tabulated by treatment group. Non-compartmental PK data analysis were to be performed for MEDI7814-treated participants to estimate PK parameters if data allowed. |
| Number of Participants With Anti-Drug Antibodies (ADAs) for MEDI7814 | Day 1, 29, 57, 85, and 106 | — |
Countries
United States
Participant flow
Pre-assignment details
Out of 125 participants enrolled, 32 participants were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo A single dose of placebo matched to MEDI7814 intravenous infusion over at least 60 minutes on Day 1. | 8 |
| MEDI7814, 1 MG/KG A single dose of MEDI7814, 1 milligram per kilogram (mg/kg) intravenous infusion over at least 60 minutes on Day 1. | 6 |
| MEDI7814, 3 MG/KG A single dose of MEDI7814, 3 mg/kg intravenous infusion over at least 60 minutes on Day 1. | 6 |
| MEDI7814, 10 MG/KG A single dose of MEDI7814, 10 mg/kg intravenous infusion over at least 60 minutes on Day 1. | 6 |
| MEDI7814, 20 MG/KG A single dose of MEDI7814, 20 mg/kg intravenous infusion over at least 60 minutes on Day 1. | 6 |
| TOTAL Total of all reporting groups | 32 |
| Total | 64 |
Baseline characteristics
| Characteristic | TOTAL | Placebo | MEDI7814, 1 MG/KG | MEDI7814, 3 MG/KG | MEDI7814, 10 MG/KG | MEDI7814, 20 MG/KG |
|---|---|---|---|---|---|---|
| Age, Continuous | 33.5 Years STANDARD_DEVIATION 9.1 | 32.3 Years STANDARD_DEVIATION 9.9 | 28.5 Years STANDARD_DEVIATION 6.8 | 36.5 Years STANDARD_DEVIATION 6.7 | 28.0 Years STANDARD_DEVIATION 8.9 | 42.8 Years STANDARD_DEVIATION 4 |
| Sex: Female, Male Female | 7 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 25 Participants | 6 Participants | 6 Participants | 5 Participants | 6 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 8 | 2 / 6 | 4 / 6 | 3 / 6 | 1 / 6 |
| serious Total, serious adverse events | 1 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to Day 106 that were absent before treatment or that worsened relative to pretreatment state. AEs included SAEs as well as non-serious AEs which occurred during the trial.
Time frame: Day 1 to Day 106
Population: Safety population included all randomized participants who received MEDI7814 and had safety data available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 4 Participants |
| Placebo | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | SAEs | 1 Participants |
| MEDI7814, 1 MG/KG | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 2 Participants |
| MEDI7814, 1 MG/KG | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | SAEs | 0 Participants |
| MEDI7814, 3 MG/KG | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 4 Participants |
| MEDI7814, 3 MG/KG | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | SAEs | 0 Participants |
| MEDI7814, 10 MG/KG | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | SAEs | 0 Participants |
| MEDI7814, 10 MG/KG | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 3 Participants |
| MEDI7814, 20 MG/KG | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 1 Participants |
| MEDI7814, 20 MG/KG | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | SAEs | 0 Participants |
Secondary
Number of Participants With Anti-Drug Antibodies (ADAs) for MEDI7814
Time frame: Day 1, 29, 57, 85, and 106
Population: Analyses of immunogenicity was not performed as the clinical development of MEDI7814 had been discontinued because the indication was no longer being pursued.
Secondary
Pharmacokinetic (PK) Parameters of MEDI7814
Individual MEDI7814 plasma concentration data and descriptive statistics of the PK parameters were to be tabulated by treatment group. Non-compartmental PK data analysis were to be performed for MEDI7814-treated participants to estimate PK parameters if data allowed.
Time frame: Predose, end of infusion, 2, 6, 12 hours post-end of infusion on Day 1; Day 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 106
Population: Analyses of PK was not performed as the clinical development of MEDI7814 had been discontinued because the indication was no longer being pursued.