First Time in Human Study of Protexia

NCT ID: NCT00744146

Last Updated: 2010-09-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

33 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-09-30

Study Completion Date

2009-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Intervention for Nerve Agent Exposure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Protexia

Intervention Type BIOLOGICAL

Single 50 mg IM dose

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.

Group Type EXPERIMENTAL

Protexia

Intervention Type BIOLOGICAL

Single 100 mg dose

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.

Group Type EXPERIMENTAL

Protexia

Intervention Type BIOLOGICAL

Two 250 mg doses, IM, one at Day 1 and one at Day 72

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.

Group Type EXPERIMENTAL

Protexia

Intervention Type BIOLOGICAL

Single 500 mg dose, IM

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.

Group Type EXPERIMENTAL

Protexia

Intervention Type BIOLOGICAL

Single 750 mg dose, IM

Interventions

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Protexia

Single 50 mg IM dose

Intervention Type BIOLOGICAL

Protexia

Single 100 mg dose

Intervention Type BIOLOGICAL

Protexia

Two 250 mg doses, IM, one at Day 1 and one at Day 72

Intervention Type BIOLOGICAL

Protexia

Single 500 mg dose, IM

Intervention Type BIOLOGICAL

Protexia

Single 750 mg dose, IM

Intervention Type BIOLOGICAL

Other Intervention Names

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PEG-rBChE PEG-rBChE PEG-rBChE PEG-rBChE PEG-rBChE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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United States Department of Defense

FED

Sponsor Role collaborator

Quintiles, Inc.

INDUSTRY

Sponsor Role collaborator

QPS Holdings LLC

INDUSTRY

Sponsor Role collaborator

PharmAthene, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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PharmAthene, Inc.

Principal Investigators

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Ralph A Schutz, MD

Role: PRINCIPAL_INVESTIGATOR

Quintiles, Inc.

Locations

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Quinitles Phase I Services

Overland Park, Kansas, United States

Site Status

Countries

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United States

Other Identifiers

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QOPK 4439

Identifier Type: -

Identifier Source: org_study_id