Results from a Global Phase 3 Trial (IB1001-303) Evaluating N-acetyl-L-leucine in Ataxia-telangiectasia
Marc Patterson1, Bethany Zanrucha1, Janelle Raymond1, Jorgji Kerthi1, Asante Hatcher1, Taylor Fields1, Ian Billington1, Michael Strupp2, Tatiana Bremova-Ertl3, Kyriakos Martakis4
1IntraBio, Inc., 2Department of Neurology, LMU University Hospital, 3Department of Neurology and Center for Rare Diseases, University Hospital Inselspital Bern, 4Department of Neuropediatrics, Justus Liebig University
Objective:

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).

Background:

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.

Design/Methods:

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.

Results:
Seventy-four participants aged 5-50 years were randomized. Topline results including baseline demographics, primary efficacy and safety data will be presented pending data availability.  
Conclusions:
IB1001-303, a global, phase 3, randomized, double-blind, crossover trial will generate important data to evaluate the efficacy and safety of NALL in people with A-T. 
10.1212/WNL.0000000000216403
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