Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Single-Dose Subcutaneous Administration of MEDI-528

Phase 1

Completed

Conditions: Healthy

Interventions: Biological: MEDI-528 1 mg/kg
Biological: MEDI-528 3 mg/kg
Biological: MEDI-528 9 mg/kg
Biological: MEDI-528 0.3 mg/kg

Registration Number: NCT00116168

Lead Sponsor: MedImmune LLC

Brief Summary: A Phase I studyto evaluate the safety and tolerability of escalating subcutaneous (SC) doses of MEDI-528 in to healthy adult volunteers.

Detailed Description: The primary objective of this Phase I study is to evaluate the safety and tolerability of escalating single SC doses of MEDI-528 administered to healthy adult volunteers in four dose groups.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 29

Inclusion Criteria

Males and females age 19 up to, and including, 49 years of age at the time of the first dose of study drug
Weight less than 89 kg
Written informed consent obtained from the volunteer
Healthy by medical history and physical examination
Sexually active females, unless surgically sterile or at least two years post-menopausal or an FSH≥40 mIu/mL, must use an effective method of avoiding pregnancy (including oral, injectable, transdermal, abstinence, use of a condom by the sexual partner or sterile sexual partner) for 3 months before the first dose of study drug, and must agree to continue using such precautions through the study period of 84 days. Cessation of birth control after this point should be discussed with a responsible physician. Sexually active males, unless surgically sterile, must likewise use an effective method of birth control (condom or abstinence) and must agree to continue using such precautions through Study Day 84 after their dose of study drug.
Use of common over-the-counter medications such as topical corticosteroids, decongestants, antihistamines, analgesics, and antacids is permitted unless, in the opinion of the investigator, it would interfere with either the volunteer's ability to complete the study or interpretation of the study results.
Ability to complete the follow-up period of 84 days
Willing to forego other forms of experimental treatment during the study period of 84 days
Willing to forego vigorous activity 1 - 2 days before dosing, and before each study visit.

Exclusion Criteria

Acute illnesses or evidence of significant active infection, such as fever greater than or equal to 38.0 C (100.5°F) at the start of the study
Use of prescription medications, other than oral contraceptives, in the 28-day period before Study Day 0
Any blood donation or significant loss of blood within 6 months of time of entry into the study
History of immunodeficiency or receipt of immunosuppressive drugs
History of allergy or reaction to any component of the MEDI-528 formulation
History of substance abuse that, in the opinion of the investigator, may compromise the ability of the study subject to complete the study and follow-up period
Evidence of any systemic disease, neurologic abnormality, lymphadenopathy, or splenomegaly upon physical examination
Evidence of infection with hepatitis A, B, or C virus or HIV-1
Receipt of immunoglobulins or blood products within 60 days of entering the study
Receipt of any investigational drug therapy or standard vaccine therapy, other than vaccination for influenza, within 60 days of the first dose of study drug through Study Day 84 (use of licensed agents for indications not listed in the package insert is permitted)
Receipt of MEDI-528 in any previous clinical study
At Screening (must be within 21 days before study dose administration) any of the following: Hgb, total WBC, platelet count, Na, K, C1, CO2, AST, ALT, BUN, glucose, amylase, lipase, creatinine, or troponin out of the normal range; other abnormal laboratory values in the screening panel that, in the opinion of the principal investigator, are judged to be clinically significant
Clinically significant abnormality, as determined by the investigator, on 12-lead electrocardiogram at the time of initial screening
Clinically significant abnormalities noted on baseline brain MRI
Elective surgery planned during the study period through Study Day 84
Pregnancy (sexually active females must have a negative serum pregnancy test on the day of the first dose of study drug, before dosing)
Nursing mother
The presence of any condition or concern which, in the opinion of the investigator, may interfere with the conduct or interpretation of the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MEDI-528 1 mg/kg	MEDI-528 1 mg/kg	MEDI-528 (1 mg/kg) administered as a single, SC dose
MEDI-528 3 mg/kg	MEDI-528 3 mg/kg	MEDI-528 (3 mg/kg) administered as a single, SC dose
MEDI-528 9 mg/kg	MEDI-528 9 mg/kg	MEDI-528 (9 mg/kg) administered as a single, SC dose
MEDI-528 0.3 mg/kg	MEDI-528 0.3 mg/kg	MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose

Primary Outcome Measures

Name	Time	Method
Incidence of Changes From Baseline in the Day 28 Magnetic Resonance Imaging (MRI) of the Brain	Days 0 and 28	Number of participants with changes from baseline in the Day 28 MRI of the brain
Incidence of Serious Adverse Events	Days 0 - 84	Number of participants experiencing serious adverse events
Incidence of Adverse Events	Days 0 - 84	Number of participants experiencing adverse events (includes both adverse events and serious adverse events)
Incidence of Abnormal Troponin Levels	Days 0, 1, 7, 14, and 28	Number of participants with troponin levels greater than upper limit of normal
Incidence of Clinically Significant Changes From Baseline in Neurologic Exam	Days 0, 7, 14, 21, 28, 42, and 84	Number of participants with clinically significant changes from baseline in neurologic exam

Secondary Outcome Measures

Name	Time	Method
Incidence of Anti-drug Antibodies (ADA) to MEDI-528	Days 0, 14, 28, 42, and 84	Number of participants with ADA to MEDI-528
Time to Observed Maximum Serum Concentration (Tmax)	Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84	Tmax of MEDI-528
Observed Maximum Serum Concentration (Cmax)	Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84	Cmax of MEDI-528
Area Under the Concentration Curve From Time Zero to Last Measurable Concentration [AUC(0-t)]	Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84	AUC(0-t) of MEDI-528
Area Under the Concentration Curve From Time Zero to Infinity [AUC(0-infinity)] of MEDI-528	Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84	AUC(0-infinity) of MEDI-528
Percent of Total Area Under the Concentration Curve Extrapolated From Last Measurable Time to Infinity [AUC(Ext)]	Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84	AUC(ext) of MEDI-528
Total Body Clearance (CL)	Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84	CL of MEDI-528
Half-life (T1/2)	Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84	T1/2 of MEDI-528
Apparent Extravascular Terminal Phase Volume of Distribution (Vz/F)	Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84	Vz/F of MEDI-528