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

Study Overview
=================
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.

Official Title
-----------------
A Phase I, Open Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Single-Dose Subcutaneous Administration of MEDI-528, a Humanized Monoclonal Anti-Interleukin-9 Antibody, in Healthy Adult Volunteers

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Biological: MEDI-528 0.3 mg/kg
* Biological: MEDI-528 1 mg/kg
* Biological: MEDI-528 3 mg/kg
* Biological: MEDI-528 9 mg/kg


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 49 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI-528 0.3 mg/kg<br>MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose | Biological: MEDI-528 0.3 mg/kg<br>* MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose<br>|
| Experimental: MEDI-528 1 mg/kg<br>MEDI-528 (1 mg/kg) administered as a single, SC dose | Biological: MEDI-528 1 mg/kg<br>* MEDI-528 (1 mg/kg) administered as a single, SC dose<br>|
| Experimental: MEDI-528 3 mg/kg<br>MEDI-528 (3 mg/kg) administered as a single, SC dose | Biological: MEDI-528 3 mg/kg<br>* MEDI-528 (3 mg/kg) administered as a single, SC dose<br>|
| Experimental: MEDI-528 9 mg/kg<br>MEDI-528 (9 mg/kg) administered as a single, SC dose | Biological: MEDI-528 9 mg/kg<br>* MEDI-528 (9 mg/kg) administered as a single, SC dose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

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

Secondary Outcome Measures

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