AB Science announced that the FDA has accepted its investigational new drug (IND) application for masitinib, and thus will proceed with a phase 3 study (AB19001) to test the agent in patients with amyotrophic lateral sclerosis (ALS).
Study AB19001 is intended to confirm results from the first phase 2b/3 AB10015 study (NCT02588677) which demonstrated that masitinib, at 4.5 mg/kg/day in combination with riluzole, significantly slowed decline as measured by the Amytrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R). Study AB19001 is planned as a prospective, multicenter, placebo-controlled, phase 3 study aimed to compare the efficacy and safety of masitinib in combination with riluzole versus placebo in combination with riluzole in the treatment of patients suffering from ALS.
“I am extremely pleased with this FDA clearance, which represents a significant milestone for the development of masitinib in ALS. Masitinib is the first drug that targets both microglia and mast cells to be evaluated in ALS. I am convinced that this approach represents a promising potential addition to our currently limited therapeutic options for patients with ALS,” Albert Ludolph, MD, international coordinator of study AB19001, professor of neurology, and chairman, department of neurology, University Hospital and Medical Facility of Ulm, in Germany, said in a statement.
Masitinib is an oral tyrosine kinase inhibitor that has demonstrated its neuroprotective capability in 2 previous studies—AB07002 and AB10015.
In February 2020, the company announced the drug had met primary end point in the phase 2b/3 AB07002 study of patients with primary progressive multiple sclerosis (PPMS) and nonactive secondary progressive MS (SPMS). In AB07002, researchers used masitinib 4.5 mg/kg/day compared with 6.0 mg/kg/day placebo and found that the drug significantly delayed disease progression as measured by the time to reach an Expanded Disability Status Scale (EDSS) score of 7.0 across a 611-participant cohort.
Now, AB19001 will enroll 495 patients who will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio. Group 1 will include patients on masitinib, titrated from a start at 3.0 mg/kg/day and escalating to 4.5 mg/kg/day, plus riluzole. The second group will take masitinib, titrated starting at 3.0 mg/kg/day and escalating to 4.5 mg/kg/day and then to 6.0 mg/kg/day, plus riluzole. Group 3 will be administered matching placebo, plus riluzole.
Researchers came to these dose conclusions from prior evidence in the AB10015 study, which showed an acceptable profile with maintenance doses of 3.0 and 4.5 mg/kg/day.
As enrollment is currently ongoing, the inclusion criteria for the study apply to patients with an ALS disease duration from diagnosis of no longer than 24 months at the screening visit, who were treated with a stable dose of riluzole (100 mg/day) for at least 12 weeks days prior to baseline visit, and who had an ALSFRS-R score progression of >0.3 per month between onset of the disease and screening.
Researchers will use change from baseline using ALSFRS-R after 48 weeks of treatment as the primary end point. Additional secondary end points include the Combined Assessment of Function and Survival (CAFS).
“That is really good news for all of us and in particular for the patients and we aim to initiate the phase 3 confirmatory trial in ALS as soon as conditions at US clinical sites stabilize post-the coronavirus pandemic,” Alan Moussy, co-founder and chief executive officer, AB Science, said in a statement.
AB Science announces that FDA clears masitinib IND in Amyotrophic Lateral Sclerosis (ALS) allowing US patient enrollment to commence in phase 3 study [news release]. Paris, France: Ab Science. March 31, 2020. Accessed April 3, 2020. globenewswire.com/news-release/2020/03/31/2009399/0/en/AB-Science-announces-that-FDA-clears-masitinib-IND-in-Amyotrophic-Lateral-Sclerosis-ALS-allowing-U-S-patient-enrollment-to-commence-in-Phase-3-study.html