Idorsia has enrolled the first patient in its MODIFY clinical trial, which will evaluate the potential of investigative oral monotherapy lucerastat as a treatment for adult patients with genetically confirmed Fabry disease.
The Phase 3 trial (NCT03425539) will assess the safety and effectiveness of lucerastat in Fabry patients older than 18. The trial, currently recruiting, is expected to enroll more than 100 participants from 29 clinical sites in nine countries. Patients will be treated with either lucerastat alone, in an adjusted dose between 250 mg and 1000 mg, or a placebo, for up to six months.
“Today’s news is an important milestone for the Fabry research and patient communities that have contributed to the development of this study,” Derralynn Hughes, PhD, coordinating investigator of the study in Europe, said in a press release. “Pain is a genuine and pressing unmet need of the Fabry patient population. Lucerastat represents an exciting potential new oral treatment option to address this.”
The main goal of the study is to demonstrate lucerastat’s potential to reduce hand and foot pain (neuropathic pain) that affects the majority of these patients and severely diminishes their quality of life. The investigators also will assess the treatment’s effectiveness in gastrointestinal symptoms and analyze plasma globotriaosylceramide (Gb3) levels, a biomarker of Fabry disease.
Upon completion of the six months of treatment, participants will have the opportunity to continue lucerastat treatment in an open label extension study, which is expected to run for approximately 20 months.
“We have worked closely with patients during the development of the MODIFY protocol for lucerastat,” said Guy Braunstein, MD, head of Global Clinical Development at Idorsia. “We conducted an international patient survey to better understand the symptoms of patients with Fabry disease, and validated a patient reported outcome instrument to specifically assess Fabry neuropathic pain, in accordance with health authority guidance.”
Preclinical studies in mice have shown that inhibition of glucosylceramide synthase — an enzyme involved in the production of Gb3 — as a consequence of lucerastat treatment could significantly prevent the accumulation of Gb3 in the kidneys and some nerve endings.
Also, experiments with cells collected from patients revealed that the investigative therapy could effectively reduce the amount of Gb3 independently of the genetic mutation that caused the disease.
Results from an exploratory Phase 1 trial (NCT02930655) further demonstrated that lucerastat, in combination with standard enzyme replacement therapies (ERTs), significantly reduced plasma Gb3 levels compared to ERTs alone.
Collectively these results provide evidence of lucerastat’s potential and support the development of the Phase 3 MODIFY study. The company also is planning an additional clinical trial to test lucerastat in children 2 to 18 years old.
“Idorsia’s preclinical data indicate that lucerastat has the potential to treat patients with Fabry disease, regardless of their specific gene mutation type. Lucerastat is therefore a potential new oral treatment option for a very broad spectrum of patients living with Fabry disease,” said Martine Clozel, MD, chief scientific officer at Idorsia.
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