Patient Dosing Underway for Phase 2 Study of RNA Aptamer BB-031 in Acute Ischemic Stroke
BB-031 aims to expand the population eligible for acute revascularization therapy by reopening blocked arteries beyond the traditional therapeutic window, potentially increasing eligible AIS patients by nearly 50%.
Michael Hill, MD
According to an announcement, patient dosing has begun for the phase 2 RAISE study (NCT06226805), a two-part trial assessing the safety and preliminary efficacy of BB-031 (Basking Biosciences), a first-in-class RNA aptamer targeting von Willebrand Factor (vWF) in patients with acute ischemic stroke (AIS). BB-031, an investigational agent, is designed to be safer, more effective, and able to significantly expand the population eligible to receive acute revascularization therapy.1
In RAISE, approximately 156 patients with AIS will be randomized to receive 1 dose of either BB-031 or placebo. In Part A, approximately 36 patients will be randomly assigned 3:1 into 1 of 3 planned ascending dose groups to determine the dose levels to be studied in Part B. Two dose levels will be chosen based upon a review of all available data including safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy. In Part B, approximately 120 participants will be randomized 1:1:1 to receive a single dose of 2 dose levels of study drug or placebo.
"Effectively and safely targeting recanalization of acutely occluded intracranial arteries with novel pharmacology has the potential to expand access to treatment for stroke patients and will address a significant unmet need in acute stroke care," principal investigator Michael Hill, MD, a professor for the Departments of Clinical Neurosciences, Community Health Sciences, Medicine, and Radiology at the University of Calgary and Foothills Medical Center, said in a statement.1 "Many patients are simply not eligible for current drug treatments or cannot reach a comprehensive stroke center in time to benefit from advanced endovascular treatment."
Research predicts that current AIS treatments reach only 15% of all patients and have significant limitations, such as a small window to treat and high risk of intracerebral hemorrhage following treatment. Device-based endovascular thrombectomy, another less used option for AIS, is limited by its ability to mechanically retrieve clots found only in the large vessels of the brain. In addition, many acute care centers lack access to technology due to the expense and infrastructure requirements for the surgical intervention.
According to Basking, BB-031 is capable of reopening blocked arteries beyond the therapeutic time window of standard of care, thus potentially increasing the eligibility of the AIS patient population for acute revascularization by nearly 50%. Prior to RAISE, a phase 1, randomized, placebo-controlled study assessing the agent in healthy volunteers laid the groundwork for future trials in patients with thrombotic conditions including AIS.
Presented at the 2024 International Stroke Conference, held February 7-9, in Phoenix, Arizona, the study featured 40 healthy volunteers who received BB-031 or placebo by intravenous bolus injection at single ascending doses of 0.1, 0.3, 1.0, 2.0, and 4.0 mg/kg. All told, BB-031 was considered safe and well-tolerated for 28 days following single intravenous doses up to 4.0 mg/kg. Overall, there were no significant adverse events (AEs) or treatment-emergent AEs. Minor events included bleeding at an intravenous site in 1 participant, and minor bleeding of an ulcer on the tongue in 1 participant.2
In the phase 1 study, BB-031 demonstrated nonlinear, dose-dependent plasma PK across the dose range tested, with an apparent mean terminal half-life of 18 min at 1 mg/kg to 67 min at 4.0 mg/kg. In addition, dose-dependent changes in vWF binding were observed, with more than 95% maximal mean change from baseline achieved in the 4.0 mg BB-031 group. Furthermore, platelet function analyzer-200 results showed complete inhibition of clot formation (closing time ≥300 seconds) at all doses tested with a dose-dependent duration of inhibition and return to normal range.
"We are thrilled to have this study underway – patients are waiting,” Shahid M. Nimjee, MD, PhD, co-founder and chief medical officer at Basking, and professor of neurosurgery and surgical director of the Comprehensive Stroke Center at The Ohio State University Wexner Medical Center, said in a statement.1 "We believe BB-031 will greatly expand the therapeutic options for stroke patients. Recanalization may also be performed more safely given that our reversal agent, BB-025, which will enter clinical development next year, has been shown in preclinical studies to neutralize BB-031 within minutes."
In January, Basking announced the close of $55 million financing to accelerate the clinical development of BB-031. In addition to the RAISE trial, the company claimed the funds will also be used to advance BB-025, a complementary rapid-acting reversal oligonucleotide capable of quickly neutralizing the pharmacological activity of BB-031, through a phase 1 clinical program.3
