Reach2HD Trial – Phase 2 Clinical Trial

Reach2HD was a randomised double-blind, placebo controlled Phase 2 clinical research trial to determine the safety and tolerability of PBT2 in patients with Huntington’s disease.

Reach2HD was a six month trial in 109 patients with early to mid-stage Huntington’s disease, across 20 sites in the US and Australia. Prana is aiming to demonstrate safety, motor and behavioural benefits, and identify where patients could show a clinical benefit from PBT2.  

Animal models of HD have indicated PBT2 may be able to improve motor function and control, increase life span and reduce brain cell deterioration. 

Prana is hopeful PBT2 can work in two ways against Huntington’s disease; prevent the accumulation of toxic huntintin proteins and the resultant damage inside neurons, and improve neuronal health and function by restoring normal copper and zinc levels which are disturbed when neurodegeneration takes place.

FDA approval to commence the Reach2HD trial of PBT2 in Huntington’s disease was granted in January 2012. Results from this Phase 2 trial are due in early 2014. 

Depending on the results of the Reach2HD trial, Prana will meet with the US regulator, the Food and Drug Administration, and other regulatory agencies to discuss the next steps in the clinical development of PBT2 as a treatment for Huntington’s disease.

Information about the trial

The Reach2HD Trial was conducted by the Huntington Study Group (HSG) under the direction of Ray Dorsey, MD, Principal Investigator, Johns Hopkins University, and Diana Rosas, MD co-Principal Investigator, Massachusetts General Hospital.

Doses of PBT2 were controlled at 100mg and 250mg per day versus a placebo to determine the safety and tolerability of PBT2. The trial also tested if PBT2 had an effect on cognitive (thinking) abilities and other HD symptoms including motor (movement).

PBT2 has show in animal modelling it can reduce the aggregation of a mutant function, preserve neuronal tissue and significantly improve life expectancy. 1,2,3


The results of the Reach2HD Phase 2 clinical trial investigating PBT2 as a treatment for Huntington disease were released in February 2014. The double-blind, placebo-controlled study was conducted by the Huntington Study Group at research sites in the United States and Australia. 

Primary Objectives: Safety and Tolerability

The primary endpoint of the study was met. In this study, PBT2 was safe and well tolerated.   Ninety-five percent (104 of 109) of participants completed the study on their assigned dose. 

An independent Data Safety Monitoring Board met on five occasions over the course of the trial and on each occasion recommended that the trial continue as per the original protocol.

There were no substantial differences in adverse events across the two PBT2 dose groups and the placebo group. Only one of the ten reported serious adverse events was deemed by the clinical site investigator to be related to drug treatment.  This occurred during the 4-week follow-up period after the treatment phase of the trial had ended.

Secondary Objectives: Efficacy
The effects of PBT2 were tested on cognition, motor performance, behaviour and functional capacity, of which cognition was pre-specified as the main efficacy outcome.

There was a statistically significant improvement in performance on the Trail Making Test Part B (as illustrated in this graph), in the PBT2 250mg group compared to placebo at both 12 (p<0.001) and 26 weeks (p=0.042).

Trail Making Test Part B measures executive function (e.g., ability to plan activities), which is impaired early in the course of Huntington disease and is also affected in Alzheimer disease.

Given the evidence from an earlier trial that showed that PBT2 improved executive function in Alzheimer’s disease patients, the Reach2HD trial included a plan to assess the effects of PBT2 on an Executive Function composite z-score that included the Trail Making Test Part B. There was a statistically significant improvement in this z-score (p=0.038) in a pre-specified analysis of Reach2HD participants with early stage Huntington disease, as measured by their Total Functioning Capacity. Across all participants, which comprised both early and mid-stage patients, there was a trend to improvement (p=0.069). 

What is PBT2?

Research has shown that certain normally occurring metals in the brain play a significant role in diseases such as Alzheimer’s disease and more recently, Huntington’s disease. 

Researchers at Prana Biotechnology have created a chemical library of small chemical agents termed ‘MPACs’ (Metal Protein Attenuating Compounds) designed to interrupt interactions between these metals and target proteins in the brain, to prevent deterioration of brain cells. Prana’s lead MPAC for Alzheimer’s Disease, PBT2, has been shown to:

  1. Prevent the metal dependent conversion of amyloid beta protein into oligomers that are toxic to synapses and;
  2. Restore normal brain metal distribution that is essential for neuronal health and synaptic function. 

Previously in a Phase 2a study, PBT2 significantly decreased beta-amyloid in the cerebrospinal fluid and significantly improved Executive Function in mild Alzheimer’s Disease patients within three months of treatment.


1. Lannfelt et al. “Safety, Efficacy, and biomarker findings of PBT2 in targeting Abeta modifying therapy for Alzheimer’s disease: a controlled Phase 2a, double-blind, randomized, placebo-controlled trial”, Lancet Neurology (2008) vol. 7, pp. 779-86.

2. Lannfelt et al. Errata: Lancet Neurology (2009) vol. 8, pp. 981.

3. Faux et al “PBT2 Rapidly Improves Cognition in Alzheimer's Disease: Additional Phase 2 Analyses”, Journal of Alzheimer’s Disease (2010) vol. 20 pp. 509-516



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