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

MedImmune LLC64 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Healthy Volunteers

Interventions

PlaceboBIOLOGICAL

Participants will receive single dose of placebo matched MEDI5884 injection SC on Day 1

MEDI5884 Dose 1BIOLOGICAL

Participants will receive single dose MEDI5884 Dose 1 injection SC on Day 1.

MEDI5884 Dose 2BIOLOGICAL

Participants will receive single dose MEDI5884 Dose 2 injection SC on Day 1

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Research Site

Glendale, California, United States

Outcomes

Primary Outcomes

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)

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort.

HDL-Cholesterol over time

Time frame: Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort.

Secondary Outcomes

Lipoprotein particle size

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Participants will receive single dose MEDI5884 Dose 3 injection SC on Day 1

MEDI5884 Dose 4BIOLOGICAL

Participants will receive single dose MEDI5884 Dose 4 injection SC on Day 1

Lipoprotein particle size

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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