PP-007 for Ischemic Stroke

(HEMERA-1 Trial)

Recruiting at13 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Prolong Pharmaceuticals

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests the safety of PP-007, a modified cow protein given through an IV, in stroke patients. It aims to improve blood flow and reduce brain damage. The study includes patients already receiving standard stroke treatments.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on anticoagulants or dual antiplatelet agents, you may need to stop them 48 hours before the trial if they lead to certain blood test results. It's best to discuss your specific medications with the trial team.

What data supports the idea that PP-007 for Ischemic Stroke is an effective treatment?

The available research shows that PP-007, also known as Sanguinate, can be effective in treating ischemic stroke. In studies with animals, it was found to reduce the size of the damaged area in the brain and improve recovery. In a Phase I trial with healthy volunteers, it was safe and well-tolerated, which means it can move on to further testing in patients. Compared to other treatments, PP-007 has shown promise in protecting the brain during a stroke by improving blood flow and reducing damage. ^{1 2 3 4 5}

What safety data is available for PP-007 (Sanguinate) treatment?

Sanguinate, also known as PEGylated bovine carboxyhemoglobin, has undergone Phase I clinical trials where it was found to be safe and well tolerated with no serious adverse events reported. The trials involved healthy volunteers receiving single ascending doses, and although serum haptoglobin decreased, it was not dose-related. Additionally, Sanguinate has been used under emergency protocols, showing improved patient status without serious adverse effects. Further safety testing in patients with Sickle Cell Disease also indicated it was well tolerated. ^{1 2 3 6 7}

Is the drug PP-007 (Sanguinate) a promising treatment for ischemic stroke?

Yes, PP-007 (Sanguinate) is a promising treatment for ischemic stroke. It helps improve blood flow to the brain, reduces damage from the stroke, and aids in faster recovery. It has been shown to be safe in early trials and is moving forward to more advanced testing. ^{1 2 3 4 5}

Research Team

Kirsten Gruis, MD

Principal Investigator

Prolong Pharmaceuticals, LLC

Eligibility Criteria

This trial is for adults who've had a recent stroke caused by a blockage in the brain's large arteries. They should have specific imaging findings, be within 24 hours of symptom onset, and have been relatively healthy before the stroke. Participants must also agree to use effective contraception.

Inclusion Criteria

AIS patient with ASPECTS ≥ 3 to 10

mRS ≤ 2 (pre-morbid), prior to onset of symptoms (self-reported or family/caregiver reported)

I am using or willing to use effective birth control during and up to 90 days after the study.

Exclusion Criteria

ASPECTS < 3 on NCCT

Clinical history, past imaging, or clinical judgment suggests that the intracranial occlusion is chronic

Employee of Prolong Pharmaceuticals or its designated clinical research organization or an employee or relative of the Investigator

Treatment Details

Interventions

• PP-007 (Hemoglobin-based Oxygen Carrier)

Trial Overview The study tests PP-007, a new drug given through IV alongside standard clot-busting treatments or mechanical clot removal. Patients will get two doses of PP-007 about one day apart to see if it improves blood flow and recovery after stroke.

Participant Groups

Group I: PP-007 along with Standard of care (SOC) Experimental Treatment 1 Intervention

The study has only single arm, wherein, patients will receive two doses of PP-007 (24 ± 6 hours apart), along with the Standard-of-care (SOC) as per the site's medical practice. SOC is defined as Intravenous thrombolysis (IVT) or Mechanical Thrombectomy (MT) or both (IVT+MT).

Who Is Running the Clinical Trial?

Prolong Pharmaceuticals

Lead Sponsor

Trials

15

Recruited

310+

Findings from Research

In a study involving 14 mongrel dogs with induced middle cerebral artery occlusion, Sanguinate significantly reduced infarct volume compared to the control group, indicating its potential efficacy in treating ischemic stroke.

Sanguinate treatment also improved relative cerebral blood flow and pial collateral recruitment, suggesting it enhances blood flow to ischemic areas, which could be beneficial in acute stroke management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of early Sanguinate (PEGylated carboxyhemoglobin bovine) infusion on cerebral blood flow to the ischemic core in experimental middle cerebral artery occlusion. Christoforidis, GA., Saadat, N., Liu, M., et al.[2022]

SANGUINATE, a PEGylated carboxyhemoglobin bovine, has shown efficacy in animal models for treating hypoxia by reducing ischemic damage in various tissues, including the heart and brain.

In a Phase I trial with 24 healthy volunteers, SANGUINATE was found to be safe and well tolerated, with no serious adverse events reported, allowing it to progress to further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PEGylated carboxyhemoglobin bovine (SANGUINATE): results of a phase I clinical trial. Misra, H., Lickliter, J., Kazo, F., et al.[2022]

In a study involving rats with induced hemorrhagic shock, SANGUINATE, a novel oxygen carrier, significantly improved survival rates compared to standard resuscitation fluids like Lactated Ringer's Solution and Hextend.

SANGUINATE also enhanced tissue oxygenation and maintained higher mean arterial pressure for a longer duration after resuscitation, indicating its potential as a more effective treatment for hemorrhagic shock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Sanguinate on Systemic and Microcirculatory Variables in a Model of Prolonged Hemorrhagic Shock. Nugent, WH., Cestero, RF., Ward, K., et al.[2020]

Transfusion of PEGylated carbon monoxide-bound hemoglobin (PEG-COHb) significantly reduced brain infarct volume in rats after a middle cerebral artery occlusion (MCAO), demonstrating its efficacy in protecting the brain compared to non-carbon monoxide PEG-hemoglobin.

PEG-COHb maintained cerebral vasodilation better than non-CO PEG-Hb, suggesting that it enhances blood flow and collateral perfusion during ischemic events, even at low transfusion volumes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transfusion of hemoglobin-based oxygen carriers in the carboxy state is beneficial during transient focal cerebral ischemia. Zhang, J., Cao, S., Kwansa, H., et al.[2021]

Transfusion of PEGylated hemoglobin (PEG-COHb) in anesthetized rats during focal cerebral ischemia significantly reduced brain infarct volume and improved neurological function, indicating its protective effects against ischemic stroke.

Despite only a slight increase in plasma hemoglobin levels (0.6 g/dL) and no change in blood pressure or red cell flux, the early transfusion of PEG-COHb demonstrated efficacy in mitigating the effects of stroke, suggesting a potential therapeutic role for PEG-Hb in stroke management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early treatment of transient focal cerebral ischemia with bovine PEGylated carboxy hemoglobin transfusion. Klaus, JA., Kibler, KK., Abuchowski, A., et al.[2021]

SANGUINATE™, a PEGylated bovine carboxyhemoglobin, is being developed as a treatment for hypoxia, showing potential to inhibit vasoconstriction and improve oxygen delivery to tissues.

Phase 1 safety trials indicated that SANGUINATE is safe and well tolerated in healthy volunteers, with no serious adverse effects, and early Phase Ib studies in Sickle Cell Disease patients showed promising improvements in their condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PEGylated Bovine Carboxyhemoglobin (SANGUINATE™): Results of Clinical Safety Testing and Use in Patients. Abuchowski, A.[2017]

Sanguinate™ (SG) significantly increased collateral blood flow in spontaneously hypertensive rats (SHR) during middle cerebral artery occlusion (MCAO), suggesting it may help improve blood supply to the brain during ischemic events.

Early treatment with SG reduced brain injury compared to vehicle treatment, indicating its potential as an effective adjunct therapy to enhance reperfusion and extend treatment windows in stroke management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologically increasing collateral perfusion during acute stroke using a carboxyhemoglobin gas transfer agent (Sanguinate™) in spontaneously hypertensive rats. Cipolla, MJ., Linfante, I., Abuchowski, A., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Effect of early Sanguinate (PEGylated carboxyhemoglobin bovine) infusion on cerebral blood flow to the ischemic core in experimental middle cerebral artery occlusion. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

PEGylated carboxyhemoglobin bovine (SANGUINATE): results of a phase I clinical trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Effects of Sanguinate on Systemic and Microcirculatory Variables in a Model of Prolonged Hemorrhagic Shock. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Transfusion of hemoglobin-based oxygen carriers in the carboxy state is beneficial during transient focal cerebral ischemia. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Early treatment of transient focal cerebral ischemia with bovine PEGylated carboxy hemoglobin transfusion. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

PEGylated Bovine Carboxyhemoglobin (SANGUINATE™): Results of Clinical Safety Testing and Use in Patients. [2017]

7. United States pubmed.ncbi.nlm.nih.gov

Pharmacologically increasing collateral perfusion during acute stroke using a carboxyhemoglobin gas transfer agent (Sanguinate™) in spontaneously hypertensive rats. [2019]