Coronary DiseasePhase 2NCT00116012
Anticoagulation With rNAPc2 to Eliminate MACE/TIMI 32
A Phase 2 study testing rNAPc2 in people with Coronary Disease, run by ARCA Biopharma, Inc. at 1 site in United States.
Trial summary
The primary focus of this study is to explore the safety of a range of doses of rNAPc2 in subjects who are managed in hospitals that most typically practice an early invasive strategy (catheterization during the index admission). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Coronary Disease
- What is being tested?
- rNAPc2
- How many people
- 300 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2005to not given
- Phase
- Phase 2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ages 18 to 75 years inclusive
- Ischemic symptoms lasting >= 5 minutes at rest within the prior 48 hours
- Able to be randomized within 48 hours of recent ischemic events
- At least one of the following criteria (A, B, or C): A. Elevation of CK-MB or troponin above upper limit of normal OR B. ST segment deviation (depression or transient elevation) of at least 0.5 mm OR C. TIMI risk score >= 3, defined as three or more of the following:
- Age >= 65;
- At least 3 of the following risk factors: hypertension, diabetes mellitus, current smoker (within 1 year), dyslipidemia, family history of premature coronary artery disease (< age 60);
Show all 13Show fewer
- Known or prior coronary artery stenosis > 50%;
- Daily aspirin use for at least 7 days;
- >= 2 ischemic episodes at rest lasting >= 15 minutes each within the prior 24 hours;
- Elevation of CK-MB OR troponin above upper limit of normal;
- ST segment deviation (depression or transient elevation) of at least 0.5 mm.
- Ability to understand and willingness to give written informed consent
- Planned early invasive strategy in the index hospitalization
Who cannot join
- Index event is ST-segment elevation MI or new LBBB
- CABG is planned within 7 days
- ACS is secondary to non-atherosclerotic mechanism (e.g. thyrotoxicosis, anemia)
- Prior participation in ANTHEM-TIMI 32, prior exposure to rNAPc2, or participation in a study with any experimental drug or device within 30 days
- Pregnancy, lactation or use of an intrauterine device (note: women of childbearing potential must have a negative b-HCG)
- Active renal disease, Cr > 4 mg/dl, or history of renal transplantation
Show all 20Show fewer
- History of a bleeding diathesis or recurrent bleeding episodes
- Medical comorbidities which place subject at risk for hemorrhage, including, but not limited to, prior cerebral hemorrhage, arteriovenous malformation, non-hemorrhagic CVA or TIA, GI bleed, active PUD, advanced liver or renal disease. Major trauma, surgery, CNS, spinal or eye surgery within 6 months, or parenchymal organ biopsy within 14 days.
- Uncontrolled hypertension (SBP > 180, DBP > 100) despite 1 hour of adequate treatment
- Gross hematuria within 1 month unless catheterized and subsequently resolved
- Chronic warfarin (INR > 1.4) or anticipated therapy for warfarin
- Platelet count < 120,000/mm3 at randomization or history of thrombocytopenia (confirm in a blue-top tube using sodium citrate)
- Significant anemia (M: Hg < 11 g/dL, F: Hg < 10 g/dL) at randomization
- Active liver disease or ALT and AST > 3 x ULN not felt to be part of presenting ACS
- Fibrinolytic agent within 24 hours or planned use of fibrinolytics
- Known allergy or intolerance to aspirin
- Known allergy to heparin, enoxaparin or pork-based products
- History of heparin-induced thrombocytopenia (type 1 or 2)
- Any condition for which the investigator feels enrollment in the study would place the subject at unacceptable risk (e.g. substance abuse)
- Part 2 ONLY: Use of LMWH or Xa inhibitor (e.g. Angiomax, Argatroban) >= 12 hours before randomization
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blind Placebo-Controlled Study to Assess the Safety of Factor VIIa/Tissue Factor Inhibitor, Recombinant Nematode Anticoagulant Protein c2 (rNAPc2), in Subjects With Non-ST-Elevation Acute Coronary Syndromes - ANTHEM (Anticoagulation With rNAPc2 to Help Eliminate MACE)/TIMI 32. Amendment #3 - A Single Arm, Open-Label Study of rNAPc2 With Reduced Doses of Unfractionated Heparin
The primary focus of this study is to explore the safety of a range of doses of rNAPc2 in subjects who are managed in hospitals that most typically practice an early invasive strategy (catheterization during the index admission). After completion of the ascending dose-ranging part of the trial and review of these data by the Data and Safety Monitoring Board (DSMB), the maximum tolerated dose of rNAPc2 will be studied in single-arm, open-label panels (approximately 25 subjects each) of rNAPc2 with descending doses of unfractionated heparin (UFH).
Read the detailed description
Acute coronary syndromes (ACS), which include unstable angina and non-ST-elevation (non-STE) myocardial infarction, represent a serious clinical condition affecting over 1,000,000 people in the US alone. The combined rate of death and myocardial infarction (MI) in ACS patients is 8-15% after one month, in spite of the best current therapy including use of low-molecular weight heparins, glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, and an early invasive strategy. Given the high prevalence of the disorder, further improvements in the outcomes in these patients are very desirable.
It is currently believed that the principle cause of the clinical symptoms characterizing ACS results from the transient thrombotic occlusion of one or more coronary vessels. Coronary thrombosis is initiated by the exposure of the protein tissue factor (TF), which can be found in the sub-endothelial layer of the blood vessel and is a major component of atherosclerotic gruel. The exposure of TF following vascular damage or rupture of a coronary atherosclerotic plaque, results in the rapid formation of the enzymatic complex composed of TF and the serine protease factor VIIa (fVIIa/TF). The fVIIa/TF complex initiates an amplified cascade of proteolytic activation steps resulting in the formation of the serine protease thrombin. The highly amplified generation of thrombin localized to the site of vascular damage or plaque rupture, coupled with the high-shear rheological environment of the coronary vessel, results in the activation and subsequent aggregation of platelets and the formation of an insoluble matrix of fibrin resulting in a platelet-rich thrombus.
The critical role of the fVIIa/TF complex in the initiation of coronary thrombosis suggests that it may be an ideal target for inhibitors that will result in an attenuation of thrombin generation and subsequent thrombus formation. Recombinant nematode anticoagulant protein c2 (rNAPc2) is a novel and potent inhibitor of fVIIa/TF that may improve current therapeutic strategies in reducing the extent of coronary thrombosis and subsequent clinical events in patients diagnosed with ACS.
- Conditions
- Coronary Disease
- Being tested
- rNAPc2
- Keywords
- acute coronary syndrome, rNAPc2, unstable angina, Non-STE myocardial infarction, ST elevation, cardiac enzymes, acute coronary syndromes, factor VIIa, tissue factor, nematode anticoagulant protein c2, anticoagulants, thrombin inhibitors, thrombosis
- Medical subject headings
- Coronary Disease, Acute Coronary Syndrome, Angina, Unstable, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rNAPc2Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the effects of a range of doses of rNAPc2 in subjects with non-STE acute coronary syndrome on safety and laboratory parameters from randomization until 7 days after the last dose of study drug
Secondary outcomes (6)
Evaluation of the effects of a range of doses of rNAPc2 on the presence of ischemia following randomization as identified via continuous ST segment (Holter) monitoring
Evaluation of the effects of a range of doses of rNAPc2 on pharmacodynamic and pharmacokinetic measures
Evaluation of the effects of rNAPc2 on major cardiovascular clinical events over the period from randomization until six months following randomization
Assessment of the ability of rNAPc2 to blunt the release of markers of necrosis
Exploration of the relationship between genetic variation and rNAPc2 efficacy
Evaluation of the efficacy and safety of rNAPc2 with reduced-dose (including no) unfractionated heparin (UFH)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2005 (estimated)
- Study startJun 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary DiseaseStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 300 participants
Sponsor and investigators
- Lead sponsor
- ARCA Biopharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- The TIMI Study Group
- Investigators
- Steven Deitcher, MD, Study director, ARCA Biopharma, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00116012
- Sponsor's protocol ID
- NUVO-0201
- Other IDs
- ANTHEM
- Status last verified
- Nov 2006
- First submitted
- 26 Jun 2005
- Last updated
- 29 Nov 2006
- Results posted
- No
Publications
Giugliano RP, Wiviott SD, Stone PH, Simon DI, Schweiger MJ, Bouchard A, Leesar MA, Goulder MA, Deitcher SR, McCabe CH, Braunwald E; ANTHEM-TIMI-32 Investigators. Recombinant nematode anticoagulant protein c2 in patients with non-ST-segment elevation acute coronary syndrome: the ANTHEM-TIMI-32 trial. J Am Coll Cardiol. 2007 Jun 26;49(25):2398-407. doi: 10.1016/j.jacc.2007.02.065. Epub 2007 Jun 11.
PubMed 17599602
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind Placebo-Controlled Study to Assess the Safety of Factor VIIa/Tissue Factor Inhibitor, Recombinant Nematode Anticoagulant Protein c2 (rNAPc2), in Subjects With Non-ST-Elevation Acute Coronary Syndromes - ANTHEM (Anticoagulation With rNAPc2 to Help Eliminate MACE)/TIMI 32. Amendment #3 - A Single Arm, Open-Label Study of rNAPc2 With Reduced Doses of Unfractionated Heparin
- ClinicalTrials.gov ID
- NCT00116012
- Acronym / sponsor ID
- NUVO-0201
- Conditions
- Coronary Disease
- Keywords
- acute coronary syndrome, rNAPc2, unstable angina, Non-STE myocardial infarction, ST elevation, cardiac enzymes, acute coronary syndromes, factor VIIa
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants
- Lead sponsor
- ARCA Biopharma, Inc.Industry (pharma, biotech, devices)
- Collaborators
- The TIMI Study Group
- Study start
- Jun 2005
- First posted
- 27 Jun 2005 (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 primary focus of this study is to explore the safety of a range of doses of rNAPc2 in subjects who are managed in hospitals that most typically practice an early invasive strategy (catheterization during the index admission). After completion of the ascending dose-ranging part of the trial and review of these data by the Data and Safety Monitoring Board (DSMB), the maximum tolerated dose of rNAPc2 will be studied in single-arm, open-label panels (approximately 25 subjects each) of rNAPc2 with descending doses of unfractionated heparin (UFH).
Detailed description
Acute coronary syndromes (ACS), which include unstable angina and non-ST-elevation (non-STE) myocardial infarction, represent a serious clinical condition affecting over 1,000,000 people in the US alone. The combined rate of death and myocardial infarction (MI) in ACS patients is 8-15% after one month, in spite of the best current therapy including use of low-molecular weight heparins, glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, and an early invasive strategy. Given the high prevalence of the disorder, further improvements in the outcomes in these patients are very desirable.
It is currently believed that the principle cause of the clinical symptoms characterizing ACS results from the transient thrombotic occlusion of one or more coronary vessels. Coronary thrombosis is initiated by the exposure of the protein tissue factor (TF), which can be found in the sub-endothelial layer of the blood vessel and is a major component of atherosclerotic gruel. The exposure of TF following vascular damage or rupture of a coronary atherosclerotic plaque, results in the rapid formation of the enzymatic complex composed of TF and the serine protease factor VIIa (fVIIa/TF). The fVIIa/TF complex initiates an amplified cascade of proteolytic activation steps resulting in the formation of the serine protease thrombin. The highly amplified generation of thrombin localized to the site of vascular damage or plaque rupture, coupled with the high-shear rheological environment of the coronary vessel, results in the activation and subsequent aggregation of platelets and the formation of an insoluble matrix of fibrin resulting in a platelet-rich thrombus.
The critical role of the fVIIa/TF complex in the initiation of coronary thrombosis suggests that it may be an ideal target for inhibitors that will result in an attenuation of thrombin generation and subsequent thrombus formation. Recombinant nematode anticoagulant protein c2 (rNAPc2) is a novel and potent inhibitor of fVIIa/TF that may improve current therapeutic strategies in reducing the extent of coronary thrombosis and subsequent clinical events in patients diagnosed with ACS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Ages 18 to 75 years inclusive
- Ischemic symptoms lasting >= 5 minutes at rest within the prior 48 hours
- Able to be randomized within 48 hours of recent ischemic events
- At least one of the following criteria (A, B, or C): A. Elevation of CK-MB or troponin above upper limit of normal OR B. ST segment deviation (depression or transient elevation) of at least 0.5 mm OR C. TIMI risk score >= 3, defined as three or more of the following:
- Ability to understand and willingness to give written informed consent
Key exclusion criteria (20 listed)
- Index event is ST-segment elevation MI or new LBBB
- CABG is planned within 7 days
- ACS is secondary to non-atherosclerotic mechanism (e.g. thyrotoxicosis, anemia)
- Prior participation in ANTHEM-TIMI 32, prior exposure to rNAPc2, or participation in a study with any experimental drug or device within 30 days
- Pregnancy, lactation or use of an intrauterine device (note: women of childbearing potential must have a negative b-HCG)
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 |
|---|---|---|
| rNAPc2 | Drug | – |
Primary outcome
Evaluation of the effects of a range of doses of rNAPc2 in subjects with non-STE acute coronary syndrome on safety and laboratory parameters from randomization until 7 days after the last dose of study drug
6 secondary outcomes
Evaluation of the effects of a range of doses of rNAPc2 on the presence of ischemia following randomization as identified via continuous ST segment (Holter) monitoring
Evaluation of the effects of a range of doses of rNAPc2 on pharmacodynamic and pharmacokinetic measures
Evaluation of the effects of rNAPc2 on major cardiovascular clinical events over the period from randomization until six months following randomization
Assessment of the ability of rNAPc2 to blunt the release of markers of necrosis
Exploration of the relationship between genetic variation and rNAPc2 efficacy
Evaluation of the efficacy and safety of rNAPc2 with reduced-dose (including no) unfractionated heparin (UFH)
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 29 Nov 2006.
- Derived from this study: PubMed 17599602Giugliano RP, Wiviott SD, Stone PH, Simon DI, Schweiger MJ, Bouchard A, Leesar MA, Goulder MA, Deitcher SR, McCabe CH, Braunwald E; ANTHEM-TIMI-32 Investigators. Recombinant nematode anticoagulant protein c2 in patients with non-ST-segment elevation acute coronary syndrome: the ANTHEM-TIMI-32 trial. J Am Coll Cardiol. 2007 Jun 26;49(25):2398-407. doi: 10.1016/j.jacc.2007.02.065. Epub 2007 Jun 11.
- Company websiteLink provided by the sponsor.
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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.
Steven Deitcher, MD study director
ARCA Biopharma, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rNAPc2 in people with Coronary Disease, run by ARCA Biopharma, 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 13 inclusion and 20 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 29 Nov 2006. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Evaluation of the effects of a range of doses of rNAPc2 in subjects with non-STE acute coronary syndrome on safety and laboratory parameters from randomization until 7 days after the last dose of study drug. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00116012, which also lists 1 linked publication.
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 29 Nov 2006.