To assess the efficacy and safety of N-acetyl-L-leucine (NALL) in people with Ataxia-Telangiectasia (A-T) in a global, phase 3, randomized, placebo-controlled, double-blind crossover trial (IB1001-303).

A-T is a rare autosomal-recessive cerebellar ataxia. NALL is a modified amino acid. NALL is ubiquitously transported, including across the blood-brain barrier to the central nervous system, and enters enzyme-controlled pathways to correct metabolic dysfunction, improve function of the lysosomal-mitochondrial axis, and restore membrane potential and cellular signaling. Clinical studies of NALL in Niemann-Pick disease type C, GM2 Gangliosidoses, and a phase 2 trial in A-T consistently demonstrate NALL significantly improves ataxia.

IB1001-303 enrolled participants with a genetically confirmed diagnosis of A-T, aged 4 years and older across ten multinational trial sites in Europe and the U.S. Participants were randomized 1:1 to receive NALL or placebo and then crossed over. Treatment was administered orally, and participants received a total daily dose of 2-4 g/day based on weight-tiered doses. The primary efficacy endpoint was the Scale for the Assessment and Rating of Ataxia (SARA). Secondary endpoints included Spinocerebellar Ataxia Function Index (SCAFI), International Cooperative Ataxia Rating Scale (ICARS), Neurology Quality of Life - Upper Extremity Function (NeuroQOL-UEF), Quality of Life (EQ-5D-5L for participants aged >18 years and EQ-5D-Y for participants aged <18 years), investigator, caregiver (if applicable), and patient Clinical Global Impression of Improvement (CGI-I) and axial SARA (gait, sitting, stance, and speech disturbance). Safety assessment included adverse event incidence and severity.