Safety Study of PP-007 in Subjects With Acute Ischemic Stroke
Safety Study of PP-007 in Subjects With Acute Ischemic Stroke
The study will evaluate the safety of a single administration of PP-007 in patients admitted
 to a hospital for Acute Ischemic Stroke. PP-007 is pegylated bovine carboxyhemoglobin and
 will be administered via IV infusion. The effects on collateral flow, infarct size and
 functional outcome will also be evaluated. Patients will be randomized to either standard of
 care excluding tPA, or PP-007. Patients may also receive thrombectomy.
The study will evaluate the safety of a single administration of PP-007 in patients admitted
 to a hospital for Acute Ischemic Stroke. PP-007 is pegylated bovine carboxyhemoglobin and
 will be administered via IV infusion. The effects on collateral flow, infarct size and
 functional outcome will also be evaluated. Patients will be randomized to either standard of
 care excluding tPA, or PP-007. Patients may also receive thrombectomy. Other measures include
 assessment of plasma concentration of PP-007.
Inclusion Criteria:

 -  1. Subject or subject's LAR has provided informed consent. 2. ≥18 years of age. 3. AIS
 diagnosis including:

 1. CTA with evidence of anterior circulation large artery occlusion (i.e., ICA
 terminus, M1, M2, A1, A2).

 2. 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.

 3. 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.

 4. 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:

 1. 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:

 a. Known hypersensitivity to radiographic contrast agents. b. 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).

 1. Platelet count <50,000/μL at Baseline.

 2. Prothrombin Time (International Normalization Ratio [INR]) ≥2 and/or activated
 partial tromboplastin time (aPTT) ≥40 seconds at Baseline.

 3. Any anticoagulants within the previous 48 hours.

 4. 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:

 a. Documented renal insufficiency (serum creatinine >3.0 × ULN). b. 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:

 1. Significant mass effect with midline shift ≥8 mm.

 2. 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.