First Time in Human Study of Protexia

PharmAthene

Status and phase

Completed

Phase 1

Conditions

Intervention for Nerve Agent Exposure

Treatments

Biological: Protexia

Study type

Interventional

Funder types

Industry

Other U.S. Federal agency

Identifiers

NCT00744146

QOPK 4439

Details and patient eligibility

About

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.

Full 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.

Enrollment

33 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

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

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

33 participants in 5 patient groups

Experimental group

Description:

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.

Treatment:

Biological: Protexia

Experimental group

Description:

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.

Treatment:

Biological: Protexia

Experimental group

Description:

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.

Treatment:

Biological: Protexia

Experimental group

Description:

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.

Treatment:

Biological: Protexia

Experimental group

Description:

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.

Treatment:

Biological: Protexia

Trial contacts and locations

Data sourced from clinicaltrials.gov

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