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

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Biological: Placebo; Biological: MEDI5884 Dose 4; Biological: MEDI5884 Dose 1; Biological: MEDI5884 Dose 2; Biological: MEDI5884 Dose 3

• Registration Number: NCT03001297
• Lead Sponsor: MedImmune LLC

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.

Study Timeline

• Study First Submitted: 2016-11-23
• Study First Submitted QC: 2016-12-19
• Study First Posted: 2016-12-23
• Study Start: 2017-01-17
• Status Verified: 2018-08
• Primary Completion: 2018-08-10
• Study Completion: 2018-08-10
• Last Update Submitted: 2018-08-21
• Last Update Posted: 2018-08-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo will be administered subcutaneously (SC).
MEDI5884 Dose 4	MEDI5884 Dose 4	Participants will receive single dose of MEDI5884 Dose 4 injection SC on Day 1.
MEDI5884 Dose 1	MEDI5884 Dose 1	Participants will receive single dose of MEDI5884 Dose 1 injection SC on Day 1.
MEDI5884 Dose 2	MEDI5884 Dose 2	Participants will receive single dose of MEDI5884 Dose 2 injection SC on Day 1.
MEDI5884 Dose 3	MEDI5884 Dose 3	Participants will receive single dose of MEDI5884 Dose 3 injection SC on Day 1.

Primary Outcome Measures

Name	Time	Method
HDL-Cholesterol over time	Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort.	HDL-Cholesterol over time
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.	Clinical laboratory assessments (serum chemistry, hematology, and urinalysis)

Secondary Outcome Measures

Name	Time	Method
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
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
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
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
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
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
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)
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
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
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
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

Trial Locations

Locations (1)

Research Site; 🇺🇸 Glendale, California, United States