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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03001297
• Other study ID #: D7870C00001
• Status: Completed
• Phase: Phase 1
• Start date: January 17, 2017
• Est. completion date: August 10, 2018

Study information

• Verified date: August 2018
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: August 10, 2018
• Est. primary completion date: August 10, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Biological:
• Placebo
Participants will receive single dose of placebo matched MEDI5884 injection SC on Day 1
• MEDI5884 Dose 1
Participants will receive single dose MEDI5884 Dose 1 injection SC on Day 1.
• MEDI5884 Dose 2
Participants will receive single dose MEDI5884 Dose 2 injection SC on Day 1
• MEDI5884 Dose 3
Participants will receive single dose MEDI5884 Dose 3 injection SC on Day 1
• MEDI5884 Dose 4
Participants will receive single dose MEDI5884 Dose 4 injection SC on Day 1

Locations

Country	Name	City	State
United States	Research Site	Glendale	California

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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