Healthy Volunteers
Conditions
Keywords
atherosclerosis; acute coronary syndrome; MEDI5884
Brief summary
A Phase 1, single dose study with 4 cohorts of ascending doses and an optional Japanese cohort designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of MEDI5884 in healthy volunteers
Detailed description
This is a first time in human, phase 1, randomized, blinded, placebo-controlled study to evaluate the safety, pharmacokinetics and pharmacodynamics of single ascending subcutaneous doses of MEDI5884 in healthy volunteers (age 18-55). The study consists of 4 cohorts of increasing doses (8 subjects each) and an optional Japanese American cohort (24 subjects) for a total of 56 healthy subjects. The decision whether or not to dose escalate will be based upon data review by the Dose Escalation Committee. Subjects will be randomized 3:1 to MEDI5884 or placebo. Following screening, the study consists of a 3 day inpatient stay and follow up visits. The number of follow up visits depend on the cohort assigned.
Interventions
BIOLOGICALPlacebo
Participants will receive single dose of placebo matched MEDI5884 injection SC on Day 1
BIOLOGICALMEDI5884 Dose 1
Participants will receive single dose MEDI5884 Dose 1 injection SC on Day 1.
BIOLOGICALMEDI5884 Dose 2
Participants will receive single dose MEDI5884 Dose 2 injection SC on Day 1
BIOLOGICALMEDI5884 Dose 3
Participants will receive single dose MEDI5884 Dose 3 injection SC on Day 1
BIOLOGICALMEDI5884 Dose 4
Participants will receive single dose MEDI5884 Dose 4 injection SC on Day 1
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers aged 18-55 years * Must provide written informed consent * Ability and willingness to adhere to the protocol * BMI 18-30kg/m2 * Females not of childbearing potential * Males must practice 2 effective contraceptive measures if sexually active * Japanese descent for the Japanese cohort
Exclusion criteria
* Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product * History or presence of gastrointestinal, renal, or hepatic disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs * Abnormal lab values, physical exam, vital signs * Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to dosing * Positive Hepatitis B, Hepatitis C or HIV test * Receipt of investigational therapy with 4 months from screening * Current or previous use of systemic corticosteroids 60 days prior to dosing or lipid lowering medications 28 days prior to dosing * Abnormal ECG * Recent plasma or blood donation * Positive drug or alcohol screen. * Current smoker
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with adverse events as a measure of safety and tolerability of MEDI5884 | Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort. | Treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs) |
| HDL-Cholesterol over time | Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort. | HDL-Cholesterol over time |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Levels of total cholesterol | Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing | Levels of total cholesterol |
| Non-HDL-Cholesterol | Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing | Non-HDL-Cholesterol |
| Low-density lipoprotein cholesterol (direct and Friedewald equation) | Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing | Low-density lipoprotein cholesterol (direct and Friedewald equation) |
| Very low-density lipoprotein cholesterol | Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing | Very low-density lipoprotein cholesterol |
| Triglycerides | Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing | Triglycerides |
| Apolipoprotein B | Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing | Apolipoprotein B |
| Lipoprotein particle size | Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing | Lipoprotein particle size |
| MEDI5884 serum concentration: maximum observed concentration | Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4) | MEDI5884 serum concentration: maximum observed concentration |
| MEDI5884 serum concentration: time to maximum observed concentration | Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4) | MEDI5884 serum concentration: time to maximum observed concentration |
| MEDI5884 serum concentration: area under the concentration time curve | Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4) | MEDI5884 serum concentration: area under the concentration time curve |
| MEDI5884 serum concentration: terminal half-life | Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4) | MEDI5884 serum concentration: terminal half-life |
| Anti-drug antibody | Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing | Anti-drug antibody |
| Apolipoprotein A1 | Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing | Apolipoprotein A1 |
| Lipoprotein particle number | Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing | Lipoprotein particle number |
Countries
United States
Outcome results
None listed