BB-031 for Stroke

(RAISE Trial)

Recruiting at 11 trial locations

Overseen By Program Director

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Basking Biosciences, Inc.

Must not be taking: Thrombolytics, Glycoprotein IIb/IIIa inhibitors

Disqualifiers: Large stroke, Hemorrhage, Coagulopathy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 day

156 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and tolerability of ascending doses (Part A) and selected doses (Part B) of BB-031 in acute ischemic stroke patients presenting within 24 hours of stroke onset. Participants will be randomized to receive one dose of either the investigational drug or placebo and will be followed for 90 days. A total of 156 patients are planned in this study.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are taking thrombolytic drugs or glycoprotein IIb/IIIa inhibitors, you may not be eligible to participate.

Is BB-031 safe for human use?

Butylphthalide, used in BB-031, is generally considered safe for preventing stroke after a transient ischemic attack (TIA), with fewer adverse reactions compared to aspirin. ^{1 2 3 4 5}

Research Team

Michael D Hill, MD

Principal Investigator

University of Calgary

Shahid Nimjee, MD

Principal Investigator

Ohio State University

Eligibility Criteria

This trial is for adults who've had a stroke within the last 24 hours, caused by a blockage in the arteries that supply blood to the front part of their brain. They must be diagnosed with an acute ischemic stroke.

Inclusion Criteria

I started having stroke symptoms less than 24 hours ago.

I have a blockage in the arteries in the front part of my brain.

I have been diagnosed with a stroke caused by a blood clot.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single dose of either the investigational drug BB-031 or placebo via IV bolus injection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of radiological outcomes and adverse events

90 days

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• BB-031

Trial Overview The study tests BB-031, a new drug, against a placebo (a substance with no active drug). Participants are randomly chosen to receive either BB-031 or placebo once and will be monitored for three months.

Participant Groups

Group I: BB-031 Experimental Treatment 1 Intervention

A single dose of BB-031 will be administered via IV bolus injection

Group II: Placebo Placebo Group 1 Intervention

A single dose of matching placebo will be administered via IV bolus injection

Who Is Running the Clinical Trial?

Basking Biosciences, Inc.

Lead Sponsor

Trials

2

Recruited

200+

Findings from Research

In a study of 57 patients with transient ischemic attack or minor stroke, mapping blood-brain barrier dysfunction (BBBD) using dynamic contrast-enhanced MRI revealed significantly higher BBBD in patients compared to healthy controls, indicating its potential as a diagnostic tool.

BBBD mapping not only correlated with clinical symptoms in 72% of patients but also predicted the risk of recurrent stroke, with a risk ratio of 5.35 for those who developed new strokes during follow-up, highlighting its importance for stroke prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood-Brain Barrier Leakage: A New Biomarker in Transient Ischemic Attacks. Serlin, Y., Ofer, J., Ben-Arie, G., et al.[2020]

3-n-Butylphthalide (NBP) and its metabolite 3-hydroxy-NBP (3-OH-NBP) can cause significant liver toxicity, with 3-OH-NBP being the most harmful, leading to cell death and oxidative stress in liver cells.

The study suggests that the liver damage from NBP can be mitigated by supplementing with glutathione (GSH) or N-acetylcysteine (NAC), and by avoiding the use of CYP3A4 inducers, which can worsen the toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Site-specific protein modification by 3-n-butylphthalide in primary hepatocytes: Covalent protein adducts diminished by glutathione and N-acetylcysteine. Xue, Y., Ren, X., Zhu, Z., et al.[2021]

The blood-brain barrier (BBB) plays a crucial role in maintaining brain health, and its breakdown is linked to the progression of stroke and other neurodegenerative diseases.

Research is advancing on BBB-targeted therapies that could help protect the brain and promote recovery after a stroke, highlighting the BBB as a key focus for both basic and clinical research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breaking the barrier in stroke: what should we know? A mini-review. Borlongan, CV., Rodrigues, AA., Oliveira, MC.[2021]

Trilobatin (TLB) effectively protects the blood-brain barrier (BBB) from disruption caused by cerebral ischaemia-reperfusion injury in a rat model, maintaining BBB integrity and reducing neuronal loss.

TLB works by increasing tight junction proteins and decreasing pro-inflammatory markers, specifically targeting MMP9 and inhibiting the APOE4/CypA/NF-κB pathway, which are crucial for its neuroprotective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trilobatin attenuates cerebral ischaemia/reperfusion-induced blood-brain barrier dysfunction by targeting matrix metalloproteinase 9: The legend of a food additive. Feng, L., Li, Y., Lin, M., et al.[2023]

In a study of 98 patients with transient ischemic attack (TIA) and positive DWI findings, butylphthalide injection significantly reduced the incidence of cerebral infarction compared to aspirin treatment, indicating its efficacy in preventing stroke.

Butylphthalide injection was found to be safe, with fewer adverse reactions reported, making it a promising option for treating TIA patients at risk of progressing to infarction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of butylphthalide injection on treatment of transient ischemic attack as shown by diffusion-weighted magnetic resonance imaging abnormality. Zhang, C., Zang, Y., Song, Q., et al.[2020]

References

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

Blood-Brain Barrier Leakage: A New Biomarker in Transient Ischemic Attacks. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Site-specific protein modification by 3-n-butylphthalide in primary hepatocytes: Covalent protein adducts diminished by glutathione and N-acetylcysteine. [2021]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Breaking the barrier in stroke: what should we know? A mini-review. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Trilobatin attenuates cerebral ischaemia/reperfusion-induced blood-brain barrier dysfunction by targeting matrix metalloproteinase 9: The legend of a food additive. [2023]

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

Effects of butylphthalide injection on treatment of transient ischemic attack as shown by diffusion-weighted magnetic resonance imaging abnormality. [2020]