First Time in Human Study of Protexia

September 16, 2010 updated by: PharmAthene, Inc.

Phase I, Randomized, Controlled, Third-party Double-blind, Dose Escalating Study of Protexia Administered Intramuscularly at One or Two Time Points in Healthy Human Volunteers

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of Protexia, an experimental drug being developed to protect soldiers against the effects of nerve agents.

Volunteers will be entered into one of five groups. Four of the groups will receive a single intramuscular dose of Protexia or saline placebo on Study Day 1 and will participate in the study for approximately 71 days. One of the groups will receive two intramuscular doses of Protexia or saline placebo - one dose on Study Day 1 and the second dose on Study Day 72. This group will participate in the study for approximately 142 days.

All volunteers will remain at the study site as an inpatient for three days after they are dosed and will be monitored closely by the study doctors and staff. After that, volunteers will return to the study site as outpatients at predetermined intervals. Groups 1, 2, 4, 5 will have a total of 6 follow-up visits and Group 3 will have a total of 12 follow-up visits.

It is expected that this study will provide important information on the safety and tolerabiity of Protexia at one and two doses.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Protexia is a pegylated form of recombinant human butyrylcholinesterase (PEG-rBChE). Butyrylcholinesterase (BChE) is a naturally-occurring enzyme found in minute quantities in the blood. PharmAthene produces PEG-rBChE from the milk of transgenic goats. The enzyme is purified from the goat milk, formulated and pegylated to create Protexia.

This is a dose escalation study of five dose levels of Protexia. Safety data through 14 days post-dosing will be evaluated by an independent Safety Monitoring Committee (SMC) prior to escalating to a higher dose. The safety and tolerability of Protexia will be assessed using the DMID Adult Toxicity Table, May 2001 (Appendix D).

If a dose limiting toxicity (DLT) is identified in any dosing group, dosing will be suspended until the AE(s) is/are assessed. The SMC will determine if the study can continue or if the previous dose will be declared the maximum tolerated dose (MTD). It is possible that an additional dosing group at a dose midway between the previous dosing group and the dose level that exceeded the MTD may be enrolled after consultation and agreement of the SMC.

Study Type

Interventional

Enrollment (Actual)

33

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Kansas
      • Overland Park, Kansas, United States, 66211
        • Quinitles Phase I Services

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy male or female volunteers aged 18 to 55 years
  • Willing to give written informed consent to participate in the study and to comply with all study requirements and procedures
  • In the opinion of the Investigator, in generally good health, based upon pre-study medical history, physical examination, electrocardiogram (ECG) and laboratory tests
  • Normal clinical chemistry, hematology and urinalysis results or clinically insignificant values during screening evaluations

  • Women of childbearing potential may be enrolled if one of the following criteria applies:

    • Using effective contraception (e.g., injectable, transdermal, vaginal ring, oral contraceptives, IUD or barrier methods) for at least three months prior to study entry, must have maintained a normal menstrual pattern for the 3 months prior to study entry and agree to continue contraception for the duration of their participation in the study.
    • Females using injectable, transdermal, vaginal ring, oral contraceptives or an IUD must agree to augment this with a barrier method for the duration of their participation in the study.
    • Is sexually abstinent
    • Is monogamous with a vasectomized partner
    • Is postmenopausal (i.e., no cycle for at least the previous 24 months and is of menopausal age (> 45 years)
    • Has not had a menstrual cycle for 12 to 24 months and is of menopausal age as described above
    • Is surgically sterilized
    • Has had a total hysterectomy a minimum of 3 months prior to dosing on Day 1

  • Females with a negative urine pregnancy test at study Screening and a negative serum pregnancy test on admission to the Phase I unit at Day -1

    • Females in Group 3 will also require a negative serum pregnancy test on Day 71 prior to receiving Dose 2

  • Sexually active male subjects may be enrolled if one of the following criteria applies:

    • Has had a vasectomy
    • Using condoms and whose partner is using an acceptable form of contraception (IUD, oral contraceptives, birth control patch or vaginal ring, injectable or implanted contraceptives, or tubal ligation [surgical sterilization]) for the duration of the study
    • Is sexually abstinent
  • Body Mass Index (BMI) 19 to 29, inclusive
  • Abstinence from alcohol for 24 hours prior to study drug administration until discharge from the Phase I unit on Day 4

Exclusion Criteria:

  • Inability to provide Informed Consent
  • Drug or alcohol abuse requiring treatment within 12 months of study screening
  • Positive drug result at time of study screening or positive alcohol result at Day -1 (and Day 71 for Group 3 subjects)
  • Use of cholinesterase inhibitors within 21 days of dosing
  • Receipt of fresh frozen plasma within three months of study screening
  • Allergy to milk or milk derived products
  • History of allergic reaction to procainamide or to its metabolite, p-aminobenzoic acid
  • Diagnosis of myasthenia gravis
  • Participation in any trial of an investigational agent within 30 days of study screening
  • Previous receipt of any investigational BChE product
  • Clinically significant medical or psychiatric condition that, in the opinion of the Investigator, may impair study participation
  • ECG with evidence of clinically significant conduction abnormalities or active ischemia at time of study screening
  • Donation of one or more pints of blood within 30 days prior to study screening
  • Known serum positivity for human immunodeficiency virus (HIV) antibodies, hepatitis B or hepatitis C
  • Extensive tattooing which would preclude adequate assessment at the injection site(s)
  • Females who are pregnant and/or breast feeding
  • Use of systemic immunosuppressive agents, such as used to treat Alzheimer's Disease, within 3 months of dosing
  • Use of dietary or herbal supplements within 3 months of dosing

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 1

Six volunteers total.

Randomized such that four volunteers will receive Protexia as a single 50 mg dose and two volunteers will receive saline placebo of the same volume on Study Day 1.

Volunteers to be followed for approximately 71 days total.
Biological: Protexia
Single 50 mg IM dose
Other Names:
  • PEG-rBChE
Biological: Protexia
Single 100 mg dose
Other Names:
  • PEG-rBChE
Biological: Protexia
Two 250 mg doses, IM, one at Day 1 and one at Day 72
Other Names:
  • PEG-rBChE
Biological: Protexia
Single 500 mg dose, IM
Other Names:
  • PEG-rBChE
Biological: Protexia
Single 750 mg dose, IM
Other Names:
  • PEG-rBChE
EXPERIMENTAL: 2

Six volunteers total.

Randomized such that four volunteers will receive Protexia as a single 100 mg dose and two volunteers will receive saline placebo of the same volume on Study Day 1.

Volunteers to be followed for approximately 71 days total.
Biological: Protexia
Single 50 mg IM dose
Other Names:
  • PEG-rBChE
Biological: Protexia
Single 100 mg dose
Other Names:
  • PEG-rBChE
Biological: Protexia
Two 250 mg doses, IM, one at Day 1 and one at Day 72
Other Names:
  • PEG-rBChE
Biological: Protexia
Single 500 mg dose, IM
Other Names:
  • PEG-rBChE
Biological: Protexia
Single 750 mg dose, IM
Other Names:
  • PEG-rBChE
EXPERIMENTAL: 3

Eight volunteers total.

Randomized such that six volunteers will receive Protexia as a single 250 mg dose and two volunteers will receive saline placebo of the same volume on Study Days 1 and 72.

Volunteers to be followed for approximately 142 days total.
Biological: Protexia
Single 50 mg IM dose
Other Names:
  • PEG-rBChE
Biological: Protexia
Single 100 mg dose
Other Names:
  • PEG-rBChE
Biological: Protexia
Two 250 mg doses, IM, one at Day 1 and one at Day 72
Other Names:
  • PEG-rBChE
Biological: Protexia
Single 500 mg dose, IM
Other Names:
  • PEG-rBChE
Biological: Protexia
Single 750 mg dose, IM
Other Names:
  • PEG-rBChE
EXPERIMENTAL: 4

Six volunteers total.

Randomized such that four volunteers will receive Protexia as a single 500 mg dose and two volunteers will receive saline placebo of the same volume on Study Day 1.

Volunteers to be followed for approximately 71 days total.
Biological: Protexia
Single 50 mg IM dose
Other Names:
  • PEG-rBChE
Biological: Protexia
Single 100 mg dose
Other Names:
  • PEG-rBChE
Biological: Protexia
Two 250 mg doses, IM, one at Day 1 and one at Day 72
Other Names:
  • PEG-rBChE
Biological: Protexia
Single 500 mg dose, IM
Other Names:
  • PEG-rBChE
Biological: Protexia
Single 750 mg dose, IM
Other Names:
  • PEG-rBChE
EXPERIMENTAL: 5

Six volunteers total.

Randomized such that four volunteers will receive Protexia as a single 750 mg dose and two volunteers will receive saline placebo of the same volume on Study Day 1.

Volunteers to be followed for approximately 71 days total.
Biological: Protexia
Single 50 mg IM dose
Other Names:
  • PEG-rBChE
Biological: Protexia
Single 100 mg dose
Other Names:
  • PEG-rBChE
Biological: Protexia
Two 250 mg doses, IM, one at Day 1 and one at Day 72
Other Names:
  • PEG-rBChE
Biological: Protexia
Single 500 mg dose, IM
Other Names:
  • PEG-rBChE
Biological: Protexia
Single 750 mg dose, IM
Other Names:
  • PEG-rBChE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety will be assessed by: - The determination of dose limiting toxicity (if reached) - Changes from baseline for clinical laboratory tests, urine tests and vital signs - Descriptive statistics for adverse events and safety parameters
Time Frame: Volunteers in 4 of 5 Groups will be followed for 72 days. Volunteeers in 1 group will be followed for 142 days.
Volunteers in 4 of 5 Groups will be followed for 72 days. Volunteeers in 1 group will be followed for 142 days.

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetics and immunogenicity will be assessed.
Time Frame: Volunteers in 4 of 5 Groups will be followed for 72 days. Volunteeers in 1 group will be followed for 142 days.
Volunteers in 4 of 5 Groups will be followed for 72 days. Volunteeers in 1 group will be followed for 142 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PharmAthene, Inc.

Collaborators

United States Department of Defense
Quintiles, Inc.
QPS Holdings LLC

Investigators

  • Principal Investigator: Ralph A Schutz, MD, Quintiles, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (ACTUAL)

July 1, 2009

Study Completion (ACTUAL)

November 1, 2009

Study Registration Dates

First Submitted

August 28, 2008

First Submitted That Met QC Criteria

August 28, 2008

First Posted (ESTIMATE)

August 29, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

September 17, 2010

Last Update Submitted That Met QC Criteria

September 16, 2010

Last Verified

September 1, 2010

More Information

Terms related to this study

Other Study ID Numbers

  • QOPK 4439

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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