Single Dose, Weight-Based, Dose-Escalation Study With Intravenous ETI-204 in Adult Volunteers

A Randomized, Double-Blind, Placebo-Controlled, Single Dose, Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of ETI-204 in Healthy Subjects

This study will determine the safety and PK of a single IV dose of ETI-204 in subjects 18 to 65 years of age. Three cohorts will be studied with subjects receiving ETI-204. This study will be randomized, double-blind and stratified by gender. Each cohort will contain 36 subjects (including at least four females), 30 who will receive ETI-204 and six who will receive placebo.

Study Overview

• Status: Completed
• Conditions: Anthrax
• Intervention / Treatment: Drug: ETI-204, "Anthim"; Drug: placebo

Detailed Description

Protocol AH-105 is a single center, randomized, double-blind, placebo-controlled, sequential, dose escalation study. It will evaluate the safety and PK of single IV doses of ETI-204 administered to approximately 108 healthy male and female subjects. At each dose level, 30 healthy subjects, including at least 4 females, will be randomly assigned to active drug, and at least 6 healthy subjects of both genders will be randomly assigned to matching placebo.

Description of Agent: ETI-204 is a monoclonal antibody (mAb) to protective antigen (PA) from Bacillus anthracis.

The study will consist of 3 phases: Screening, Inpatient, and Outpatient Follow-up. Enrollment criteria will be determined during the 21-day Screening Phase (Visit 1), following by a 3 night inpatient phase where eligible subjects will receive a single dose of IV ETI-204 or matching placebo as described above and undergo routine safety monitoring, dermatologic assessments, and blood draws at pre-specified time points. Subjects will be discharged from the center after collection of the 48-hour PK sample. During the subsequent 70-day outpatient follow-up phase, subjects will return to the center on Days 8, 15, 29, 43 and 71 for clinical laboratory testing (hematology and clinical chemistry), physical examinations and vital signs measurements, and routine safety monitoring. Blood samples for PK and anti-drug antibodies (ADA)will also be collected. The 70 day post-dosing follow-up in this study was selected to allow characterization for the PK profile of ETI-204 and the potential development of ADA.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Quintiles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria: Subjects who meet all of the criteria shown below may be included in the study.

1. Healthy male or female subjects between 18 and 65 years of age.
2. Subjects with a body mass index (BMI) > 18.5 and < 35 kg/m2.
3. Female subjects of childbearing potential (not post-menopausal or surgically sterile) must have a negative urine β-hCG pregnancy test at Screening.
4. Female subjects of childbearing potential (not post-menopausal or surgically sterile) must use a medically accepted method of contraception for the duration of the study, including the 70-day follow-up period. Acceptable methods of contraception include abstinence, a barrier method with spermicide, an intrauterine device (IUD) or a hormonal contraceptive (oral, transdermal, implanted, or injected) in conjunction with a barrier method.
5. Male subjects must agree to practice abstinence or to use a condom with spermicide for the duration of the study, including the 70-day follow-up period.
6. The subject has no clinically significant abnormalities on the clinical laboratory tests (hematology, clinical chemistry, or urinalysis) or ECG at Screening.
7. Subject provides written informed consent.

Exclusion Criteria:Subjects who meet any of the criteria below will be excluded from participation in the study.

1. Subject requires regular use of a medication for a chronic condition.
2. Subject has a clinically significant comorbidity that would interfere with the completion of the study procedures or objectives, or would compromise the subject's safety.
3. Subject has a systolic blood pressure (BP) > 140 mm Hg or a diastolic BP > 90 mm Hg.
4. Subject has a systolic BP < 90 mm Hg.
5. Subject has current suspected drug or alcohol abuse as specified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) (American Psychiatric Association 2000).
6. Subject has a positive alcohol or drug test result at Screening and on Day -1
7. Subject has received an investigational agent within 30 days or 5 half-lives (whichever is longer) of Screening.
8. Subject has congenital or acquired immunodeficiency syndrome.
9. Subject has a positive test for Hepatitis B (surface antigen), Hepatitis C, or human immunodeficiency virus (HIV) at Screening.
10. Subject smokes > 3 cigarettes per day.
11. Subject has ever had prior treatment for anthrax exposure, prior anthrax infection, prior immunization with any anthrax vaccine or prior treatment with an investigational anthrax treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ETI-204; ETI-204, Anthim	Drug: ETI-204, "Anthim"; intravenously, single dose; Other Names: ETI-204
Sham Comparator: placebo	Drug: placebo; intravenously, single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Objective	To evaluate the safety of increasing doses of ETI-204 in healthy subjects	71 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Objective	To evaluate the PK of increasing singles doses of ETI-204 in healthy subjects. To evaluate the immunogenicity of ETI-204 following IV administration in healthy subjects.	71 days

Collaborators and Investigators

• Sponsor: Elusys Therapeutics
• Investigators: Principal Investigator: Eleanor A Lisbon, M.D., M.P.H, Quintiles Phase One Services

Publications and helpful links

General Publications

• Nagy CF, Leach TS, Hoffman JH, Czech A, Carpenter SE, Guttendorf R. Pharmacokinetics and Tolerability of Obiltoxaximab: A Report of 5 Healthy Volunteer Studies. Clin Ther. 2016 Sep;38(9):2083-2097.e7. doi: 10.1016/j.clinthera.2016.07.170. Epub 2016 Aug 24.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: October 14, 2011
• First Submitted That Met QC Criteria: October 17, 2011
• First Posted (Estimate): October 18, 2011

Study Record Updates

• Last Update Posted (Actual): November 14, 2017
• Last Update Submitted That Met QC Criteria: November 9, 2017
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Bacillaceae Infections; Anthrax
• Other Study ID Numbers: AH105