Intervention for Nerve Agent ExposurePhase 1NCT00744146
First Time in Human Study of Protexia
A Phase 1 study testing Protexia in people with Intervention for Nerve Agent Exposure, run by PharmAthene, Inc. at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Intervention for Nerve Agent Exposure
- What is being tested?
- Protexia
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2008to Nov 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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 locations and contacts
1 site in 1 country.
United States1 site
Quinitles Phase I Services
Overland Park, Kansas, 66211
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Intervention for Nerve Agent Exposure
- Being tested
- Protexia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProtexiaBiological
Also called PEG-rBChE
Single 50 mg IM dose
ProtexiaBiological
Also called PEG-rBChE
Single 100 mg dose
ProtexiaBiological
Also called PEG-rBChE
Two 250 mg doses, IM, one at Day 1 and one at Day 72
ProtexiaBiological
Also called PEG-rBChE
Single 500 mg dose, IM
ProtexiaBiological
Also called PEG-rBChE
Single 750 mg dose, IM
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | 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. Receives: Biological: Protexia |
| 2 | Experimental | 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. Receives: Biological: Protexia |
| 3 | Experimental | 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. Receives: Biological: Protexia |
| 4 | Experimental | 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. Receives: Biological: Protexia |
| 5 | Experimental | 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. Receives: Biological: Protexia |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Volunteers in 4 of 5 Groups will be followed for 72 days. Volunteeers in 1 group will be followed for 142 days.
Secondary outcomes (1)
Pharmacokinetics and immunogenicity will be assessed.
Measured: Volunteers in 4 of 5 Groups will be followed for 72 days. Volunteeers in 1 group will be followed for 142 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2008 (estimated)
- Study startSep 2008
- Primary completionJul 2009
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intervention for Nerve Agent ExposureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- PharmAthene, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- United States Department of Defense, Quintiles, Inc., QPS Holdings LLC
- Investigators
- Ralph A Schutz, MD, Principal investigator, Quintiles, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00744146
- Sponsor's protocol ID
- QOPK 4439
- Status last verified
- Sep 2010
- First submitted
- 28 Aug 2008
- Last updated
- 17 Sep 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00744146
- Acronym / sponsor ID
- QOPK 4439
- Conditions
- Intervention for Nerve Agent Exposure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- PharmAthene, Inc.Industry (pharma, biotech, devices)
- Collaborators
- United States Department of Defense, Quintiles, Inc., QPS Holdings LLC
- Study start
- Sep 2008
- Primary completion
- Jul 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 29 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: ProtexiaSix 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. |
| 2 | Experimental | Biological: ProtexiaSix 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. |
| 3 | Experimental | Biological: ProtexiaEight 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. |
| 4 | Experimental | Biological: ProtexiaSix 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. |
| 5 | Experimental | Biological: ProtexiaSix 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (21 listed)
- 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:
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProtexiaAlso: PEG-rBChESingle 50 mg IM dose | Biological | 1 |
| ProtexiaAlso: PEG-rBChESingle 100 mg dose | Biological | 2 |
| ProtexiaAlso: PEG-rBChETwo 250 mg doses, IM, one at Day 1 and one at Day 72 | Biological | 3 |
| ProtexiaAlso: PEG-rBChESingle 500 mg dose, IM | Biological | 4 |
| ProtexiaAlso: PEG-rBChESingle 750 mg dose, IM | Biological | 5 |
Primary outcome
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.
1 secondary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2010.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ralph A Schutz, MD principal investigator
Quintiles, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Protexia in people with Intervention for Nerve Agent Exposure, run by PharmAthene, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Sep 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2010.