Dose Escalation Study of Valortim® (MDX-1303) Administered Intravenously (IV) in Healthy, Normal Subjects

A Phase I, Double-blind, Randomized, Placebo Controlled, Dose Escalation Study of Valortim® (MDX-1303) Administered Intravenously (IV) as a 120 Minute Infusion in Healthy, Normal Subjects

Valortim is the name of the experimental drug that volunteers will receive in this study. Valortim may also be called MDX-1303. Experimental means that the drug is not yet approved by the Food and Drug Administration (FDA). Valortim is a monoclonal antibody (laboratory-made immune system molecule) for the treatment of inhalation anthrax (when the infection starts in the lungs). Valortim works by attaching itself to part of the anthrax toxin preventing the toxin from doing damage to cells. This study is being conducted to see if Valortim given over 120 minutes is safe and tolerable. This study will take place in five parts: Screening Phase, Check-in Phase (the day you arrive at Quintiles to start the study), Treatment Phase (the time when you receive the study medication), Follow-up Phase (the time after you receive the study medication) and Final Visit.

Study Overview

• Status: Completed
• Conditions: Anthrax
• Intervention / Treatment: Biological: MDX1303; Drug: Normal Saline for Injection

Detailed Description

Twenty-eight subjects will be recruited and entered into one of three dose groups 1mg/kg, 5mg/kg, 10mg/kg or placebo. Subjects will be stagger dosed into one of the three groups and randomly assigned to receive Valortim or saline. Subjects will reside in the clinical trial Phase I Unit from Day -1 through Day 2. After discharge on Day 2, all subjects will return to the Phase I unit 7 times at specified time points over an additional 130 days post-dosing (133 days total participation from check-in on Day -1)or placebo.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66223
      • Quintiles Phase I Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1.Subject must have read, understood, and provided written informed consent 2.Subjects should be in generally good health, based upon pre-study medical history, physical examination, laboratory testing and ECG 3.Laboratory screening values (i.e., hematology, clinical chemistries and urinalysis tests) must be within study-defined ranges 4.No detectable antibody to B. anthracis Protective Antigen (PA-IgG) as measured by ELISA testing at study Screening 5.Women of childbearing potential and sexually active males may be enrolled if protocol specific contraceptives or practices are met 6.Agreement to not receive any vaccinations Day -1 through to 29 days post dosing. Vaccination against B. anthracis is prohibited during the study.8.Body Mass Index (BMI) ≥ 19 and ≤ 30. 9. Abstinence from alcohol for 24 hours prior to study drug

Exclusion Criteria:

1. Prior known or suspected exposure to B. anthracis 2. Prior vaccination for B. anthracis 3.Prior exposure to Valortim as part of a previous clinical trial 4.Immunoglobulin E (IgE) level at screening that is above the upper limit of normal per the laboratory's reference range 5. History of drug or alcohol abuse, i.e., having been treated either in an in-patient or out-patient facility within 12 months of study Screening 6. Outward signs of active allergies or upper respiratory infection 7. History of dizziness or fainting upon standing (orthostatic hypotension) which, in the opinion of the Investigator, may interfere with safety evaluations 8. Positive drug result and/or positive alcohol result at time of study Screening or at Day -1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Valortim; Valortim 1mg,5mg,10mg	Biological: MDX1303; a sterile solution at a protein concentration of 25 mg/mL: 20 mM sodium citrate, 50 mM sodium chloride, 3.0% mannitol, 50 µM diethylenetriamine pentacetic acid and 0.06% polysorbate 80 at pH 6.5. A tubular, clear glass vial, filled with a 5 mL dose of colorless to pale yellow solution. The vial is sealed with a 20 mm stopper and white flip-off seal.
Placebo Comparator: Placebo; Saline solution will be used as the placebo	Drug: Normal Saline for Injection; Equivalent amounts to subjects weight, once over 120 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Determination of changes from baseline for clinical laboratory tests and urinalysis, body temperature, heart rate, blood pressure, respiratory rate, physical examination and electrocardiogram (ECG).; Occurrence and evaluation of adverse events and serious adverse events.	133 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	Evaluation of the pharmacokinetics/pharmacodynamics of Valortim in healthy human volunteers	133 days

Collaborators and Investigators

• Sponsor: PharmAthene, Inc.
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH); Department of Health and Human Services
• Investigators: Principal Investigator: Ralph Schutz, MD, Quintiles Phase I Services; Study Director: Valeire D Riddle, MD, Sponsor Medical Monitor

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: December 17, 2010
• First Submitted That Met QC Criteria: December 21, 2010
• First Posted (Estimate): December 23, 2010

Study Record Updates

• Last Update Posted (Estimate): December 9, 2013
• Last Update Submitted That Met QC Criteria: December 6, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Phase I
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Bacillaceae Infections; Anthrax
• Other Study ID Numbers: 0036-10-01; HHSN272200700033C (Other Identifier: HHSN); BAA-NIH-NIAID-DMID-07-37 (Other Grant/Funding Number: BAA-NIH-NIAID-DMID-07-37)