The phase 4 study will enroll 300 patients with amyotrophic lateral sclerosis who have started treatment with edaravone (Radicava; Mitsubishi Tanabe Pharma America).
Details from the phase 4 REFINE-ALS biomarker study in patients with amyotrophic lateral sclerosis (ALS) were presented at the Motor Neurone Disease Association 32nd International Symposium on ALS/motor neurone disease (MND), held virtually from December 7-10, 2021. Two presentations covered biomarker assays utilized in the study and COVID-19 mitigation strategies that were deployed through protocol amendments, Mitsubishi Tanabe Pharma America (MTPA) announced.1
The REFINE-ALS trial (NCT04259255) is anticipated to enroll approximately 300 patients with ALS who have begun treatment with edaravone (Radicava; MTPA). The 24-week study will include a total of 6 treatment cycles, each spanning 28 days, with 60 mg of edaravone administered by intravenous (IV) infusion for 14 days of the initial treatment cycle and followed by daily dosing on 10 out of 14 days in subsequent cycles. Biomarkers will be assessed for oxidative stress, inflammation, and neuronal and muscle injury, prior to treatment initiation, at treatment start, and again at cycles 1, 3, and 6 over the course of the study period (FIGURE).
“ALS patient needs remain MTPA’s primary focus, so it was a priority to address the evolving concerns of the ALS community during the pandemic and offer appropriate alternatives for patients to participate in the REFINE-ALS study through a virtual setting,” Atsushi Fujimoto, president, MTPA, said in a statement.1 “The collective goal has always remained twofold – ensuring the safety of the participants while continuing to foster scientific research, including the use of optimized biomarker assays to obtain real-world data and help better understand this progressive disease.”
Due to the COVID-19 pandemic, protocol amendments were implemented in January 2021, allowing patients to participate virtually via telemedicine rather than visiting hospitals or attending office visits. Samples are collected by trained nurses either at the clinic or at patients’ homes, then processed and shipped to a central collection company.
Conducted with the Massachusetts General Hospital, in collaboration with the Neurological Clinical Research Institute (NCRI) in Boston, 30 sites across North America were actively participating in the study as of April 2021. Eligible patients must be 18 years or older, having made the decision to start edaravone treatment prior to trial screening.
“Researchers have faced many challenges over the last year, but our commitment to learning more about ALS and response to treatment with Radicava in a real-world setting has remained constant,” primary investigator James Berry, MD, MPH, MGH NCRI, Boston, said in a statement.1 “Our ongoing, adaptable collaboration with MTPA has allowed the REFINE-ALS study to continue enrollment and analyses of these complex biomarkers as a way to enhance understanding of ALS treatment.”
Early intervention with IV edaravone was found to reduce death, tracheostomy, permanent assisted ventilation (PAV), and hospitalization in patients with ALS, findings from a previous study, Study 19 (NCT01492686), suggest. The 24-week double-blind period compared edaravone treatment with placebo, followed by a 24-week open-label period where all patients received IV edaravone.2
Investigators, led by Benjamin Brooks, MD, medical director, Atrium Health Neurosciences Institute, Carolinas Medical Center, presented findings at the virtual Muscular Dystrophy Association’s Scientific and Clinical Conference 2021, March 15-18, having conducted a post-hoc analysis to assess effects of IV edaravone and milestone effects in ALS, as well as survival analyses of death, tracheostomy, PAV, and hospitalization due to ALS progress.
No deaths occurred during the double-blind period, but during the open-label period, there were 2 deaths (2.9%) in the edaravone-edaravone (EE) group and 4 deaths (5.9%) in the placebo-edaravone (PE) group. HRs for death were 0.48 (95% CI, 0.08-2.73; P = .4059) in the EE, compared with the PE group.
Brooks and colleagues determined the HR for the cumulative occurrence of death, tracheostomy, or PAV to be 0.44 (95% CI, 0.10-1.81; P = .2523) in the EE group (n = 3; 4.3%) compared with the PE group (n = 6; 8.8%). Adding hospitalization to the cumulative survival analysis yielded a statistically significant HR of 0.47 (95% CI, 0.25-0.88; P = .0189) in the EE group (n = 20; 29.0%) compared with the PE group (n = 27; 39.7%).