N-Acetyl-L-Leucine for GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease)

Summary

This is a multinational, multicenter, open-label, rater-blinded prospective Phase II study which will assess the safety and efficacy of N-Acetyl-L-Leucine (IB1001) for the treatment of GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease). There are two phases to this study: the Parent Study, and the Extension Phase. The Parent Study evaluates the safety and efficacy of N-Acetyl-L-Leucine (IB1001) in the symptomatic treatment of GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease). The Extension Phase evaluates the long-term safety and efficacy of IB1001 for the neuroprotective, disease-modifying treatment of GM2 Gangliosidosis. The Extension Phase was considered exploratory.

Timeline

Start

2019-06-07

Primary completion

2023-01-09

Completion

2023-01-09

Outcome

Met primary endpoint

paper The study met its CI-CS primary end point (mean difference 0.71, SD = 2.09, 90% CI 0.00, 1.50, p = 0.039) PMID 36456200 ↗

release “First positive clinical trial for GM2 Gangliosidosis – IB1001 demonstrated a statistically significant and clinically meaningful change in both the primary and secondary endpoints” intrabio.com ↗

Publications

• Martakis K, Abreu NJ, Baker JJ, Baker Ii PR, Billington I, Burrow TA, Factor M, Fields T, Fields C, Gannon JL, Grosso M, Kerthi J, Patterson MC, Shayota BJ, Strupp M, Strupp L, Bremova-Ert T. Neurofilament light chain (NfL) as a surrogate outcome measure for GM2 gangliosidoses. J Neurol. 2026 Jul 17;273(8):467. doi: 10.1007/s00415-026-13984-x.
• Martakis K, Claassen J, Gascon-Bayari J, Goldschagg N, Hahn A, Hassan A, Hennig A, Jones S, Kay R, Lau H, Perlman S, Sharma R, Schneider S, Bremova-Ertl T. Efficacy and Safety of N-Acetyl-l-Leucine in Children and Adults With GM2 Gangliosidoses. Neurology. 2023 Mar 7;100(10):e1072-e1083. doi: 10.1212/WNL.0000000000201660. Epub 2022 Dec 1.
• Churchill GC, Strupp M, Factor C, Bremova-Ertl T, Factor M, Patterson MC, Platt FM, Galione A. Acetylation turns leucine into a drug by membrane transporter switching. Sci Rep. 2021 Aug 4;11(1):15812. doi: 10.1038/s41598-021-95255-5.
• Fields T, Patterson M, Bremova-Ertl T, Belcher G, Billington I, Churchill GC, Davis W, Evans W, Flint S, Galione A, Granzer U, Greenfield J, Karl R, Kay R, Lewi D, Mathieson T, Meyer T, Pangonis D, Platt FM, Tsang L, Verburg C, Factor M, Strupp M. A master protocol to investigate a novel therapy acetyl-L-leucine for three ultra-rare neurodegenerative diseases: Niemann-Pick type C, the GM2 gangliosidoses, and ataxia telangiectasia. Trials. 2021 Jan 22;22(1):84. doi: 10.1186/s13063-020-05009-3.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	trenonacog alfa	Protein / enzyme biologic	2 g	Oral
Subject	trenonacog alfa	Protein / enzyme biologic	3 g	Oral
Subject	trenonacog alfa	Protein / enzyme biologic	4 g	Oral

Indications