PP-007 for Ischemic Stroke

(HEMERA-1 Trial)

No longer recruiting at 13 trial locations

Overseen By Italo Linfante, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Prolong Pharmaceuticals

Must not be taking: Anticoagulants, Dual antiplatelets

Disqualifiers: Intracranial hemorrhage, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PP-007 (also known as Sanguinate or PEGylated bovine carboxyhemoglobin) for individuals who have experienced an ischemic stroke, where a blood clot blocks blood flow to the brain. The goal is to determine if PP-007 is safe when combined with standard treatments like clot-busting drugs or surgery to remove the clot. Eligible participants have recently had a disabling stroke, live independently, and can attend follow-up visits. This study is crucial as it examines how PP-007 might improve blood flow, reduce brain damage, and enhance recovery. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that PP-007 is likely to be safe for humans?

Research has shown that PP-007, when combined with standard treatments like clot-busting drugs or mechanical clot removal, is generally well-tolerated. Studies have found that patients receiving PP-007 experienced better outcomes without major safety issues. Reports from earlier studies suggested that the treatment is safe, with patients responding well. Significant side effects have not been linked to PP-007, making it a promising option for those with a sudden stroke caused by a blocked artery. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ischemic stroke?

Unlike the standard of care for ischemic stroke, which typically involves intravenous thrombolysis (IVT) or mechanical thrombectomy (MT), PP-007 is unique because it combines an innovative approach with these existing treatments. Researchers are excited about PP-007 because it offers a novel mechanism of action that could enhance the effectiveness of standard therapies. By potentially improving outcomes when used alongside IVT or MT, PP-007 aims to target the stroke more effectively and provide better recovery results for patients. This complementary use could lead to faster recovery times and improved neurological function, making it a promising addition to current stroke management strategies.

What evidence suggests that PP-007 might be an effective treatment for ischemic stroke?

Studies have shown that PP-007 can improve blood flow in the brain's backup blood vessels. These smaller vessels supply blood when a main artery is blocked, which is crucial during an acute ischemic stroke. In this trial, participants will receive PP-007 along with standard care, including Intravenous thrombolysis (IVT), Mechanical Thrombectomy (MT), or both. Research indicates that combining PP-007 with standard care significantly improves patient recovery. Early data suggest that PP-007 might reduce the size of the brain area affected by the stroke. Overall, these findings offer hope that PP-007 can aid in better recovery after a stroke. ^{1 2 6 7 8}

Who Is on the Research Team?

Kirsten Gruis, MD

Principal Investigator

Prolong Pharmaceuticals, LLC

Are You a Good Fit for This Trial?

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)

At the time of stroke, patient must be living in their own home, apartment or seniors lodge where no nursing care/support is required

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive two doses of PP-007 infusion 24 ± 6 hours apart, in addition to standard of care (IVT or MT or both)

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cardiovascular events, bleeding incidences, and clinical activity assessments

90 days

Multiple visits (in-person and virtual)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• PP-007

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.

How Is the Trial Designed?

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).

PP-007 is already approved in United States for the following indications:

Approved in United States as PP-007 for:

• Acute Ischemic Stroke (under Fast Track designation)

Who Is Running the Clinical Trial?

Prolong Pharmaceuticals

Lead Sponsor

Trials

15

Recruited

310+

Published Research Related to This Trial

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]

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]

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™ (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]

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]

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]

Citations

1. ahajournals.org ahajournals.org/doi/10.1161/SVIN.123.001246

A Prospective, Randomized Phase 1 Clinical Trial Rodent middle cerebral artery occlusion models have demonstrated that PP‐007 increases blood flow in the collateral circulation and reduces ...

2. firstwordpharma.com firstwordpharma.com/story/6327135

Prolong Pharmaceuticals to Present Phase 1/2 Data from ... According to the latest data, PP-007, when administered in adjunct to standard of care, demonstrated significantly improved functional outcomes ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04677777

Safety Study of PP-007 in Subjects With Acute Ischemic ... PP-007 is PEGylated bovine carboxyhemoglobin and will be administered via IV infusion. The effects on collateral flow, infarct size and functional outcomes ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12379620/

PMC - PubMed Central Preliminary data presented here suggest that Sanguinate administered in the early phases of acute ischemic stroke improves CBF and pial ...

5. withpower.com withpower.com/trial/phase-1-ischemic-stroke-2-2021-abd3a

PP-007 for Ischemic Stroke (HEMERA-1 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 ...

6. biospace.com biospace.com/press-releases/prolong-pharmaceuticals-to-present-phase-1-2-data-from-hemera-1-for-pp-007-in-acute-ischemic-stroke-ais-at-the-2025-world-stroke-conference-wsc

Prolong Pharmaceuticals to Present Phase 1/2 Data from ... According to the latest data, PP-007, when administered in adjunct to standard of care, demonstrated significantly improved functional outcomes ...

7. empr.com empr.com/news/pegylated-bovine-carboxyhemoglobin-fast-tracked-for-acute-ischemic-stroke/

PEGylated Bovine Carboxyhemoglobin Fast Tracked for ... The FDA has granted Fast Track designation to PP-007 (PEGylated carboxyhemoglobin, bovine) for the treatment of acute ischemic stroke.

8. jnis.bmj.com jnis.bmj.com/content/17/Suppl_1/A292

LB-001 Hemera-1 (CarboxyHEMoglobin OxygEn delivery ... Conclusions IV administration of PP-007 was well tolerated by acute stroke patients undergoing MT including patients who received IV tPA or TNK and patient who ...