Abstract Details

To report efficacy and safety results from the pivotal, Phase 3 trial investigating levacetylleucine in people living with Ataxia-Telangiectasia (A-T).

A-T is a rare, autosomal recessive cerebellar ataxia. Levacetylleucine (N-acetyl-L-leucine) is a modified amino acid that enters enzyme-controlled pathways to correct metabolic dysfunction, improve function of the lysosomal-mitochondrial axis, and restore membrane potential and cellular signaling. The Phase 3, randomized, double-blind, placebo-controlled trial (IB1001-303) evaluated the safety and efficacy of levacetylleucine in pediatric and adult individuals with A-T.

IB1001-303 enrolled A-T participants aged 4 years or older across 10 multinational trial sites. 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), and investigator, caregiver, and patient Clinical Global Impression of Improvement (CGI-I). Safety assessment included adverse event incidence and severity.

Seventy-three participants aged 4 to 50 were enrolled. The primary endpoint was met; mean change in the SARA total score with levacetylleucine was -1.92 (SD=2.81) and -0.14 (SD=2.38) with placebo; Linear Mixed Model (LMM) treatment effect -1.88 (SE=0.41) [95% confidence interval [CI] -2.70, -1.06; P<0.001]. The trial met key secondary endpoints, including ICARS (95% CI: -4.87, -0.81; P=0.003) and Investigators’ CGI-I (95% CI -0.7, 0.0; P=0.02). No treatment emergent adverse events occurred in more than 10% of participants on levacetylleucine and no serious adverse events or deaths occurred in either group.

Levacetylleucine demonstrated a significant benefit versus placebo, and clinically meaningful improvements in neurological manifestations of A-T, functioning, and quality of life, and a favorable benefit-risk profile for the treatment of A-T. Levacetylleucine was observed to be safe and well-tolerated, consistent with its established safety profile.