Effect of PBT2 in Patients With Early to Mid Stage Huntington Disease

Summary

Huntington disease (HD) is an inherited neurodegenerative disease which affects over 30,000 people in both the United States and Australia. HD is characterized by brain cell death that usually begins between the ages of 30 to 50, and results in motor, cognitive and behavioral signs and symptoms. While there are medications to help relieve some of the disease symptoms, there is no known treatment to address the cognitive impairment associated with HD. Normally occurring metals in the brain play a significant role in diseases such as Alzheimer disease and HD. PBT2 is a drug designed to interrupt interactions between these biological metals and target proteins in the brain, to prevent deterioration of brain cells. PBT2, has shown in animal models, and as well as in a small group of patients with Alzheimer's disease, it may improve cognition. There is some indication in animal models of HD, that the drug may improve motor function and control and reduce the amount of brain cell degeneration. PBT2-203 will evaluate how safe and well tolerated PBT2 is at a dose of 100 mg or 250 mg a day administered as oral daily capsules compared to a placebo over a six month treatment period. The trial will also measure whether there is an effect on cognitive abilities as well as other HD symptoms including motor and overall functioning of individuals with HD.

Timeline

Start

2012-04

Primary completion

2013-07

Completion

2014-02

Publications

• Background Lannfelt L, Blennow K, Zetterberg H, Batsman S, Ames D, Harrison J, Masters CL, Targum S, Bush AI, Murdoch R, Wilson J, Ritchie CW; PBT2-201-EURO study group. Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2008 Sep;7(9):779-86. doi: 10.1016/S1474-4422(08)70167-4. Epub 2008 Jul 30.
• Background Faux NG, Ritchie CW, Gunn A, Rembach A, Tsatsanis A, Bedo J, Harrison J, Lannfelt L, Blennow K, Zetterberg H, Ingelsson M, Masters CL, Tanzi RE, Cummings JL, Herd CM, Bush AI. PBT2 rapidly improves cognition in Alzheimer's Disease: additional phase II analyses. J Alzheimers Dis. 2010;20(2):509-16. doi: 10.3233/JAD-2010-1390.
• Huntington Study Group Reach2HD Investigators. Safety, tolerability, and efficacy of PBT2 in Huntington's disease: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2015 Jan;14(1):39-47. doi: 10.1016/S1474-4422(14)70262-5. Epub 2014 Nov 14.
• Cherny RA, Ayton S, Finkelstein DI, Bush AI, McColl G, Massa SM. PBT2 Reduces Toxicity in a C. elegans Model of polyQ Aggregation and Extends Lifespan, Reduces Striatal Atrophy and Improves Motor Performance in the R6/2 Mouse Model of Huntington's Disease. J Huntingtons Dis. 2012;1(2):211-9. doi: 10.3233/JHD-120029.

Drugs

Indications