Phase 1, Single Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MEDI5884

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1 Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses of MEDI5884 in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: Placebo
* Biological: MEDI5884 Dose 1
* Biological: MEDI5884 Dose 2
* Biological: MEDI5884 Dose 3
* Biological: MEDI5884 Dose 4


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI5884 Dose 1<br>Participants will receive single dose of MEDI5884 Dose 1 injection SC on Day 1. | Biological: MEDI5884 Dose 1<br>* Participants will receive single dose MEDI5884 Dose 1 injection SC on Day 1.<br>|
| Placebo Comparator: Placebo<br>Placebo will be administered subcutaneously (SC). | Biological: Placebo<br>* Participants will receive single dose of placebo matched MEDI5884 injection SC on Day 1<br>|
| Experimental: MEDI5884 Dose 2<br>Participants will receive single dose of MEDI5884 Dose 2 injection SC on Day 1. | Biological: MEDI5884 Dose 2<br>* Participants will receive single dose MEDI5884 Dose 2 injection SC on Day 1<br>|
| Experimental: MEDI5884 Dose 3<br>Participants will receive single dose of MEDI5884 Dose 3 injection SC on Day 1. | Biological: MEDI5884 Dose 3<br>* Participants will receive single dose MEDI5884 Dose 3 injection SC on Day 1<br>|
| Experimental: MEDI5884 Dose 4<br>Participants will receive single dose of MEDI5884 Dose 4 injection SC on Day 1. | Biological: MEDI5884 Dose 4<br>* Participants will receive single dose MEDI5884 Dose 4 injection SC on Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events as a measure of safety and tolerability of MEDI5884 | Treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs) | Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort. | 
| Number of subjects with adverse events as a measure of safety and tolerability of MEDI5884 | 12 lead electrocardiogram (ECG) including RR (The time between corresponding points on 2 consecutive R waves on ECG), PR (ECG interval measured from the onset of the P wave to the onset of the QRS complex) , QRS (ECG interval measured from the onset of the QRS complex to the J point) , QT (ECG interval measured from the onset of the QRS complex to the end of the T wave), and QTc (QT interval corrected for heart rate) intervals | Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort. | 
| Number of subjects with adverse events as a measure of safety and tolerability of MEDI5884 | Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory rates) | Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort. | 
| Number of subjects with adverse events as a measure of safety and tolerability of MEDI5884 | Clinical laboratory assessments (serum chemistry, hematology, and urinalysis) | Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort. | 
| HDL-Cholesterol over time | HDL-Cholesterol over time | Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lipoprotein particle size | 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 number | 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 | 
| Levels of total cholesterol | 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 | 
| Non-HDL-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 | 
| Low-density lipoprotein cholesterol (direct and Friedewald equation) | 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 | 
| Very low-density lipoprotein cholesterol | 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 | 
| Triglycerides | 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 | 
| Apolipoprotein B | 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 A1 | 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 | 
| MEDI5884 serum concentration: maximum observed concentration | 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: time to 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: area under the concentration time curve | 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: terminal half-life | 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) | 
| Anti-drug antibody | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atherosclerosis; acute coronary syndrome; MEDI5884