- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04677777
Safety Study of PP-007 in Subjects With Acute Ischemic Stroke (HEMERA-1)
A Randomized, Phase 1, Contemporaneously Controlled, Multicenter Study to Assess the Safety of PP-007 in Subjects With Acute Ischemic Stroke
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
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Florida
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Jacksonville, Florida, United States, 32207
- Baptist Health Research Institute
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Miami, Florida, United States, 33176
- Baptist Health South Florida
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Georgia
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Atlanta, Georgia, United States, 30303
- Grady Memorial Hospital
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Oregon
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Portland, Oregon, United States, 97239
- Oregon Stroke Center at OHSU
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213
- UPMC Stroke Institute
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
1. Subject or subject's LAR has provided informed consent. 2. ≥18 years of age. 3. AIS diagnosis including:
- CTA with evidence of anterior circulation large artery occlusion (i.e., ICA terminus, M1, M2, A1, A2).
- Large volumes of absolute hypo-perfused mismatch tissue (Tmax >10 s lesion - rCBF<30% lesion) >50 mL and core volumes ≤70 mL on CT Perfusion (CTP) and/or ASPECT score 5.
- Thrombolysis in Cerebral Infarction 0-1 flow in the intracranial internal carotid artery, M1 or M1-M2 segment of the middle cerebral artery, or carotid terminus confirmed by CTA and CTP that is accessible to thrombectomy.
- Last seen well ≤24 hours prior to start of investigational product (IP) infusion.
Note: Onset is defined as the time point when symptoms first began, or if unknown, the last time point when the subject reported or was observed having normal neurological function.
4. Modified Rankin Score ≤2, prior to the onset of symptoms (self-reported or family/caregiver reported).
5. Subject has an anticipated life expectancy of at least three months, in the opinion of the Investigator.
6. Subject and caregiver are available for protocol required follow-up visits. 7. Contraception and pregnancy:
- Male subjects, and females of childbearing potential (subjects and female partners of male subjects who are ovulating, premenopausal, and not surgically sterile) must use a highly effective method of contraception consistently and correctly during study participation and up to 90 days following PP-007 infusion.
Highly effective methods of contraception are those that, either alone or in combination, result in a failure rate of <1% per year when used consistently and correctly, including:
i. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (i.e., oral, intravaginal, or transdermal).
ii. Progesterone-only hormonal contraception associated with inhibition of ovulation (i.e., oral, injectable, or implantable).
iii. Intrauterine device, intrauterine hormone-releasing system, or bilateral tubal occlusion.
iv. Male sterilization performed more than six months prior to Screening. v. Sexual abstinence. c. Female subjects of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before Screening) or postmenopausal, defined as spontaneous amenorrhea for at least 12 months.
d. Male subjects must abstain from sperm donation during study participation and up to 90 days following PP-007 infusion.
e. Female subjects of childbearing potential must have negative results for the pregnancy test at Screening/Baseline.
Exclusion Criteria:
1. ASPECTS < 5 on NCCT. 2. Bilateral middle cerebral artery stroke. 3. Evidence of intracranial hemorrhage, including subarachnoid hemorrhage, on initial CTA/CTP, or history of intracranial hemorrhage within the last 30 days.
4. Subjects who have received or are scheduled to receive tPA use for current stroke.
5. Pre-existing neurological or psychiatric disease that would confound neurological or functional evaluations in the opinion of the Investigator.
6. A seizure at stroke onset that precludes obtaining at accurate Screening NIHSS and mRS assessment.
7. History of severe head injury within 90 days of Baseline with residual neurological deficit at the time of AIS.
8. Clinically significant heart disease including:
a. Symptoms or ECG evidence of acute myocardial infarction or unstable angina. b. Cardiac arrhythmia associated with hemodynamic instability. c. Heart failure (New York Heart Association Class III or IV) or known ejection fraction <30%.
d. ECG with second- or third-degree heart block in the absence of a permanent pacemaker.
9. Refractory BP (systolic >200 and/or diastolic >120 mmHg). 10. Confirmed diagnosis of septic embolus or bacterial endocarditis within the past six months.
11. Aortic dissection. 12. Known history of arterial tortuosity, pre-existing stent, and/or other arterial disease which would prevent the device from reaching the target vessel and/or preclude safe recovery of a device.
13. Contraindication to radiographic imaging procedures including:
- Known hypersensitivity to radiographic contrast agents.
Known renal insufficiency precluding repeated contrast administration. 14. Prior treatment (within the last 30 days) or planned concurrent treatment with an investigational medication or device.
15. Blood glucose <50 mg/dL (2.78 mmol) or >400 mg/dL (22.20 mmol) that is not responsive to appropriate treatment at Baseline.
16. Known bleeding disorder (e.g., coagulopathy or thrombocytopenia).
a. Platelet count <50,000/μL at Baseline. b. Prothrombin Time (International Normalization Ratio [INR]) ≥2 and/or activated partial tromboplastin time (aPTT) ≥40 seconds at Baseline.
c.Any anticoagulants within the previous 48 hours that leads to Prothrombin Time (International Normalization Ratio [INR]) ≥2.0 and/or activated partial thromboplastin time (aPTT) ≥40 sec at baseline.
d. Any dual antiplatelet agents (e.g., aspirin plus clopidogrel) within the previous 48 hours.
17. History or current evidence of renal or hepatic disease including:
- Documented renal insufficiency (serum creatinine >3.0 × ULN).
History of liver disease (i.e., alanine transaminase [ALT] and/or Aspartate transaminase (AST) >2 × ULN and/or conjugated bilirubin >1.5 mg/dL).
Note: A subject without history or current evidence of renal or hepatic disease does not require creatinine, ALT, AST, or bilirubin results to be available prior to enrollment.
18. Mass effect or intracranial mass on NCCT defined as:
a. Significant mass effect with midline shift ≥8 mm. b. Evidence of intracranial mass (except for small non-clinically significant meningioma based on the Investigator's discretion).
19. Employee of Prolong Pharmaceuticals or its designated clinical research organization or an employee or relative of the Investigator.
20. Any condition or situation which may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study in the opinion of the Investigator.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Standard of Care
Patients randomized to receive this treatment will receive standard of care appropriate for the condition.
|
Patients randomized to this treatment will not receive the experimental treatment, but will receive the standard of care at the institution.
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Experimental: PP-007
Patients randomized to receive this treatment will receive a single infusion of PP-007
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PP-007 is pegylated carboxyhemoglobin
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Vital Signs
Time Frame: 90 days
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Change from baseline in systolic and diastolic blood pressure in mm Hg
|
90 days
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Heart-rate
Time Frame: 90 days
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Change from baseline in heart-rate in bpm
|
90 days
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12-lead ECG
Time Frame: 90 days
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Change from baseline in msec for QT, QTc, RR and PR intervals
|
90 days
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Clinically significant change from baseline in Biochemical, hematological, coagulation and urinalysis measures
Time Frame: 90 days
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Number of subjects with clinically significant change from baseline in Biochemical, hematological, coagulation and urinalysis measures
|
90 days
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Mortality
Time Frame: 90 days
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Number of mortalities
|
90 days
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Symptomatic intracranial hemorrhage
Time Frame: 90 days
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Incidence of symptomatic intracranial hemorrhage, number of occurrences
|
90 days
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Major Bleeding incidence
Time Frame: 90 days
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Number of occurrences
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90 days
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Adverse Events
Time Frame: 90 days
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Presence or absence
|
90 days
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Bleeding requiring surgical intervention
Time Frame: 90 days
|
Number of occurrences
|
90 days
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Bleeding requiring intravenous vasoactive drugs
Time Frame: 90 days
|
Number of occurrences
|
90 days
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Intracranial hemorrhage
Time Frame: 90 days
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Number of occurrences
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90 days
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Intraocular bleed compromising vision
Time Frame: 90 days
|
Number of occurrences
|
90 days
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Fatal bleeding
Time Frame: 90 days
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Number of occurrences
|
90 days
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AESI, Blood pressure
Time Frame: 90 days
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Number of events of systolic blood pressure [SBP] >220 mmHg or diastolic blood pressure [DBP] >120 mmHg
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90 days
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AESI, Liver panel
Time Frame: 90 days
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Number of events of Liver enzymes elevation >3.0 × Baseline or upper limit of normal [ULN]
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90 days
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AESI, neurological deterioration
Time Frame: 90 days
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Number of occurrences of Neurological deterioration (≥4-point increase from Baseline in National Institutes of Health Stroke Scale.
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90 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Activity, ASITN collateral score
Time Frame: 90 days
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American Society of Interventional and Therapeutic Neuroradiology collateral score (CT Change from baseline in angiography [CTA] Score 0-4 pre- and post-dose
|
90 days
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Clinical Activity
Time Frame: 90 days
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Non-contrast computed tomography (NCCT 24 hours)
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90 days
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Clinical Activity, NIHSS and mRS
Time Frame: 90 days
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Change from baseline in NIHSS and mRS score
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90 days
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Plasma Concentration of PP007
Time Frame: 24 hours
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Plasma PP007 concentration in mg/mL at end of infusion and 24 h post infusion
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24 hours
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Clinical Activity, eTICI
Time Frame: 90 days
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Change from baseline in Expanded treatment in cerebral infarction (eTICI) score 2b or 3 post-thrombectomy change
|
90 days
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Clinical Activity, infarct growth
Time Frame: 90 days
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Predicted infarct growth for CT/CTP and collateral score
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90 days
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Prayag N Shah, MD, MBA, Prolong Pharmaceuticals, LLC
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- PIS007-101
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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