Dose-Escalation Study With ETI-204
Title: Randomized, Placebo-Controlled, Double-Blind, Dose-Escalation Phase I Study of the Safety, Tolerability and Pharmacokinetics of a Single Intravenous Dose of ETI-204 (AnthimTM)
Population: This study will determine the safety, tolerability and pharmacokinetics of a single iv dose of ETI-204 in subjects 18 to 50 years of age. Three cohorts will be studied sequentially: subjects receiving 120 mg, 240 mg and 360 mg of ETI-204. The study will be randomized, double-blind, and stratified by gender. Each cohort will contain 15 subjects (including at least four females), twelve who will receive ETI-204 and three who will receive placebo.
Study Objectives: To determine the safety, tolerability and pharmacokinetics of ETI-204 following a single intravenous administration.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Randomized, Placebo-Controlled, Double-Blind, Dose-Escalation Phase I Study of the Safety, Tolerability and Pharmacokinetics of a Single Intravenous Dose of ETI-204 (AnthimTM) [Elusys Protocol Number AH-102]|
- Evidence of clinical safety following the infusion [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]
- immunogenicity [ Time Frame: 42-70 days ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2009|
|Study Completion Date:||September 2009|
|Primary Completion Date:||July 2009 (Final data collection date for primary outcome measure)|
Drug: ETI-204, "Anthim"
single intravenous infusion of 120, 240 or 360 mg of ETI-204
|Sham Comparator: placebo||
single intravenous infusion
Study Duration: Maximum 70 days for each subject (from enrollment to end of follow-up period), unless the Day 70 HAHA (human anti-humanized antibodies) is positive, in which case subjects will be followed until HAHA test results are negative. This does not represent the total study duration, which is determined by the screening period and enrollment rate.
Description of Agent: ETI-204 is a monoclonal antibody (MAb) to protective antigen (PA) from Bacillus anthracis.
Schedule of Evaluations: Blood for pharmacokinetics (antibody concentration): Predose and at the following times after the start of infusion: 60 minutes (i.e., at the completion of the infusion), 3, 6, 12, 24 and 48 hours and on Days 7, 14, 21, 42, 56 and 70.
Blood chemistry, hematology, and urinalysis (referred to as safety laboratory assessments in the schedule of events), and urine drug screen (including ethanol and cotinine at all visits): Screening, Day 0, immediately pre-dose and on the following days after the start of infusion: 7, 14, 21, and 42. Urine pregnancy tests for all females will be performed at screening, baseline, immediately pre-dose and at 42 days. Tests of coagulation and viral serology tests will be done at screening only.
ECG: A 12-lead ECG will be done at screening. In subjects with acceptable ECG parameters, continuous 24-h Holter monitoring. will be then performed. After enrollment, a standard 12-lead ECG recording will be performed on study Day 1 (predose, 1.5h, 2h, 4h, 8h and 12h ±20 min) and continuous ECG telemetry monitoring beginning approximately 2 hours prior to the start of infusion and continuing at least 14 hours after the start of infusion. ECG is also recorded at the following study Days: 2, 7, 14, 21, and 42.
Measurement of product specific human anti-humanized antibodies (HAHA): Pre-dose and 42 days after dosing. HAHA positive subjects on Day 42 will be followed bi-weekly until study Day 70 and then monthly until HAHA test results are negative.
Vital signs (BP, P, T, RR): Screening, Day 0, before and at the following times after the start of the infusion on study day 1: 15, 30, 45, 60, 90±3 minutes; 2h,4h,8h, 12h and 24h±10 minutes (Day 2); Days 7, 14, 21 and 42.
Screening for Local and Systemic Adverse Events: The infusion site and proximal areas will be inspected for evidence of erythema, edema, visible or palpable cord, etc. on study days 1, 2, 7, 14, 21 and 42.
Participating Sites: The Ohio State University Clinical Pharmacology Unit Columbus, Ohio