Phase II/III randomized trial of TCH346 in patients with ALS

R. Miller, Walter G Bradley, M. Cudkowicz, J. Hubble, V. Meininger, H. Mitsumoto, D. Moore, H. Pohlmann, D. Sauer, V. Silani, M. Strong, M. Swash, E. Vernotica, Neil Cashman, Andrew Eisen, Charles Krieger, Angela Genge, Sanjay Kalra, John Turnbull, Lucette LacomblezWilliam Camu, Alain Destee, Albert Christian Ludolph, Reinhard Dengler, Thomas Meyer, Adriano Chio, L. H. Van Den Berg, M. De Visser, Francois Vingerhoets, Orla Hardiman, N. Leigh, Jeremy Shefner, William David, Michael Graves, Terry Heiman-Patterson, Hans Neville, Jeffrey Rosenfeld, Mark Bromberg, Andrea Corse, Andrew Waclawik, Erik Pioro, Robert Sufit, Stanley Appel, Robert Pascuzzi, John Kissel, Carlayne Jackson, Richard Barohn

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

BACKGROUND: TCH346 exerts antiapoptotic effects by binding to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and blocking the apoptotic pathway in which GAPDH is involved. Apoptosis is considered to be a key pathogenic mechanism in neurodegenerative diseases including ALS. METHODS: Patients were randomly assigned in a double-blind fashion to receive either placebo or one of four doses of TCH346 (1.0, 2.5, 7.5, or 15 mg/day) administered orally once daily for at least 24 weeks. The primary outcome measure was the rate of change in the revised ALS functional rating scale (ALSFRS-R). The trial design included a 16-week lead-in phase to determine each patient's rate of disease progression. The between treatment comparison was adjusted for the individual pretreatment rates of progression. The study was powered to detect a 25% reduction in the rate of decline of the ALSFRS-R as compared with placebo. Secondary outcome measures included survival, pulmonary function, and manual muscle testing (MMT). RESULTS: Five hundred ninety-one patients were enrolled at 42 sites in Europe and North America. There were no differences in baseline variables. There were no significant differences between placebo and active treatment groups in the mean rate of decline of the ALSFRS-R or in the secondary outcome measures (survival, pulmonary function, and MMT). CONCLUSION: The trial revealed no evidence of a beneficial effect of TCH346 on disease progression in patients with ALS.

Original languageEnglish
Pages (from-to)776-784
Number of pages9
JournalNeurology
Volume69
Issue number8
DOIs
StatePublished - Aug 1 2007

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Miller, R., Bradley, W. G., Cudkowicz, M., Hubble, J., Meininger, V., Mitsumoto, H., Moore, D., Pohlmann, H., Sauer, D., Silani, V., Strong, M., Swash, M., Vernotica, E., Cashman, N., Eisen, A., Krieger, C., Genge, A., Kalra, S., Turnbull, J., ... Barohn, R. (2007). Phase II/III randomized trial of TCH346 in patients with ALS. Neurology, 69(8), 776-784. https://doi.org/10.1212/01.wnl.0000269676.07319.09