Evaluation of the safety and efficacy of miglustat for the treatment of Chinese patients with Niemann-Pick disease type C: A prospective, open-label, single-arm, phase IV trial.

Niemann-Pick disease type C (NPC) is a rare, autosomal recessive, neurodegenerative disease associated with a wide variety of progressive neurological manifestations. Miglustat has demonstrated efficacy to delay progressive neurological deterioration in patients with NPC. We conducted a multicenter, open-label, single-arm, phase IV, post-approval commitment study to evaluate the efficacy and safety of miglustat among Chinese patients with NPC. Eligible patients were aged ≥ 4 years with an established diagnosis of NPC with two type C1 or C2 pathogenic markers or one marker with a positive biomarker (oxysterol, lysosphingolipids, or bile acids) and high clinical suspicion of NPC. Patients received oral miglustat ranging from 100 mg twice daily to 200 mg three times daily. The primary outcome was change in horizontal saccadic eye movement parameters from baseline to week 52. Seventeen patients were enrolled (median age: 14.0 years). From baseline to week 52, mean saccadic peak acceleration and velocity increased by 19.2% and 12.5%, respectively, while mean peak duration and linear regression decreased by 6.5% and 15.6%, respectively. By week 52, ambulation, manipulation, language, swallowing, and ocular movements had improved or stabilized versus baseline. All patients experienced treatment-emergent adverse events (TEAEs). Treatment-related TEAEs were reported in 12 patients with the most common being diarrhea ( = 12). Two patients died due to accidental death and asphyxia unrelated to miglustat treatment. This study demonstrated disease stabilization in Chinese patients with NPC receiving miglustat. Safety findings were consistent with miglustat's known safety profile. The study was registered at (NCT03910621).