Study to Evaluate the Safety, Tolerability,Immunogenicity, and Pharmacokinetics of MEDI-528 in Healthy Adult Volunteers

Study Overview
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Brief Summary
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Phase I study to evaluate the safety and tolerability of escalating single IV doses of MEDI-528.

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

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

Conditions
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Asthma

Intervention / Treatment
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* 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
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Eligibility Criteria
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Inclusion Criteria: Males and females age 18 up to and including 49 years of age at the time of the first dose of study drug Weight < 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 one year post-menopausal, must use an effective method of avoiding pregnancy (including oral, injectable, transdermal or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap,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 84 days after their dose of study drug. 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 84 days 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 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 Exclusion Criteria: Acute illnesses or evidence of significant active infection, such as fever ≥38.0°C (100.5°F) at the start of the study Use of prescription medications, other than contraceptives, in the 28-day period before Study Day 0 Blood donation in excess of 400 mL within 6 months of the time of entry into the study History of use of tobacco products within 3 years of Study Day 0 or history of smoking of >10 pack-years History of immunodeficiency or receipt or current use of immunosuppressive drugs including systemic corticosteroids History of allergic disease or reactions likely to be exacerbated by any component of the Study Drug (described in the Investigator's Brochure) 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 on 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 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) Any of the following: CBC: Hgb < 12.0 gm/dL; WBC < 4,000/mm3; platelet count <125,000/mm3 (or laboratory normal values); Na, K, Cl, CO2, AST, ALT, BUN, 4-hour fasting glucose, amylase, lipase, creatinine, troponin > upper limit of normal; other abnormal laboratory values in the screening panel which 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 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 the study drug, before dosing) Nursing mother The presence of any acute or chronic organ-specific condition or any concern, which in the opinion of the investigator, may interfere with the conduct or interpretation of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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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, intravenous (IV) dose | Biological: MEDI-528 0.3 mg/kg<br>* MEDI-528 (0.3 mg/kg) administered as a single, intravenous (IV) dose<br>|
| Experimental: MEDI-528 1 mg/kg<br>MEDI-528 (1 mg/kg) administered as a single, IV dose | Biological: MEDI-528 1 mg/kg<br>* MEDI-528 (1 mg/kg) administered as a single, IV dose<br>|
| Experimental: MEDI-528 3 mg/kg<br>MEDI-528 (3 mg/kg) administered as a single, IV dose | Biological: MEDI-528 3 mg/kg<br>* MEDI-528 (3 mg/kg) administered as a single, IV dose<br>|
| Experimental: MEDI-528 9 mg/kg<br>MEDI-528 (9 mg/kg) administered as a single, IV dose | Biological: MEDI-528 9 mg/kg<br>* MEDI-528 (9 mg/kg) administered as a single, IV dose<br>|

What is the study measuring?
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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 (> 0.05 ng/mL) | Days 0, 7, 14, 21, 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 who had ADA detected at each time point | Days 14, 28, 42, and 84 | 
| Time to Observed Maximum Serum Concentration (Tmax) | Tmax of MEDI-528 | Days 0 (prior to and after the end of the infusion, and at 1, 2, 4, 8, and 12 hours after the end of the infusion), 1, 3, 5, 7, 10, 14, 21, 28, 42, and 84 | 
| Observed Maximum Serum Concentration (Cmax) | Cmax of MEDI-528 | Days 0 (prior to and after the end of the infusion, and at 1, 2, 4, 8, and 12 hours after the end of the infusion), 1, 3, 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 (prior to and after the end of the infusion, and at 1, 2, 4, 8, and 12 hours after the end of the infusion), 1, 3, 5, 7, 10, 14, 21, 28, 42, and 84 | 
| Area Under the Concentration Curve From Time Zero to Infinity [AUC(0-infinity)] | AUC(0-infinity) of MEDI-528 | Days 0 (prior to and after the end of the infusion, and at 1, 2, 4, 8, and 12 hours after the end of the infusion), 1, 3, 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 (prior to and after the end of the infusion, and at 1, 2, 4, 8, and 12 hours after the end of the infusion), 1, 3, 5, 7, 10, 14, 21, 28, 42, and 84 | 
| Total Body Clearance (CL) | CL of MEDI-528 | Days 0, 1, 3, 5, 7, 10, 14, 21, 28, 42, and 84 | 
| Half-life (T1/2) | T1/2 of MEDI-528 | Days 0, 1, 3, 5, 7, 10, 14, 21, 28, 42, and 84 | 
| Terminal Phase Elimination Rate (Vz) | Vz of MEDI-528 | Days 0, 1, 3, 5, 7, 10, 14, 21, 28, 42, and 84 |