Effect of PBT2 in Patients With Early to Mid Stage Huntington Disease (Reach2HD)
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.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomized, Double-blind, Placebo-controlled Study to Assess the Safety and Tolerability, and Efficacy of PBT2 in Patients With Early to Mid-stage Huntington Disease|
- Safety and Tolerability of PBT2 in Patients With HD [ Time Frame: Baseline to 26 weeks ]As measured by the total number of participants in each dose group who reported at least one adverse events during the study,
- Change From Baseline in Cognitive Test Battery - Composite z Scores [ Time Frame: Baseline to 26 weeks ]Cognition composite z-scores were calculated for each participant. The composite scores were defined as the mean of the individual z-scores for the various cognition assessments. The Main Composite z-score was calculated for Category Fluency Test, Trail Making Test Part B, Map Search, Symbol Digit Modalities Test and Stroop Word Reading Test. The Exploratory Composite z-score was calculated for Category Fluency Test, Trail Making Test Part B, Map Search, Symbol Digit Modalities Test, Stroop Word Reading Test and Speeded Tapping test. The Executive Function Composite z-score was calculated from Category Fluency Test and Trail Making Test Part B. There is no unit of measure for the z score as it is the pure number calculated from the SD from the mean. A higher z score indicates an improvement.
- Change From Baseline in Motor Function [ Time Frame: Baseline to 26 weeks ]Total motor score calculated from the Unified Huntington Disease Rating Scale - Motor Function. The motor section of the UHDRS assesses motor features of HD with standardized ratings of oculomotor function, dysarthria, chorea, dystonia, gait, and postural stability. The total motor impairment scores is the sum of all the individual motor ratings, with higher scores indicating more severe motor impairment than lower scores. A maximum score of 60 is possible (range 0-60).
- Change From Baseline in Functional Abilities [ Time Frame: Baseline to 26 weeks ]
Total Functional Capacity (TFC) assessment was based on an individual's ability to perform common daily tasks. TFC score range was 0 to 13.
Higher scores on the function scales indicate better functioning than lower scores.
- Change From Baseline in Behaviour [ Time Frame: Baseline to 26 weeks ]Total Behavioural score from the Unified Huntington Disease Rating Scale. The behavioural assessment measures the frequency and severity of symptoms related to affect, thought content and coping styles. The total behaviour score is the sum of all responses, with scale range of 0 to 8. Higher scores on the behaviour assessments indicate more severe disturbance than lower scores.
- Change From Baseline in Investigator Global Assessments by Efficacy Index [ Time Frame: Baseline to 26 weeks ]Global function was assessed by the Investigator using the clinical global impression (CGI) scale which included assessing the severity of illness and global improvement and calculating the efficacy index for each participant. The efficacy index aims to relate therapeutic effects to reported side effects as assessed by the Investigator (range from 0 [marked improvement and no side effects] to 4 [unchanged or worse] and side effects outweigh therapeutic effects) and is calculated for each participant by dividing the therapeutic effect score by the side effects score. An improvement is reflected by CGI scale Efficacy Index values >1.
- Change From Baseline in Blood Biomarkers [ Time Frame: Baseline to 26 weeks ]Biomarkers assessed primarily with mutant huntingtin protein, normalised to lysate protein concentrations, as a change from baseline.
- Change From Baseline in Brain Function (MRI) [ Time Frame: Baseline to 26 weeks ]Measure of whole brain iron concentrations.
- Change From Baseline in Blood Biomarkers [ Time Frame: Baseline to 26 weeks ]Biomarkers assessed primarily with soluble huntingtin protein, normalised to lysate protein concentrations, as a change from baseline.
- Change From Baseline in Blood Biomarkers - Selenium [ Time Frame: Baseline to 26 weeks ]Biomarkers assessed primarily with plasma selenium as a change from baseline.
- Change From Baseline in Urine Biomarkers [ Time Frame: Baseline to 26 weeks ]Biomarkers assessed primarily with 8-hydroxy-2'-deoxyguanosine, normalised to creatinine concentrations, as a change from baseline.
- Change From Baseline in Brain Function (MRI) [ Time Frame: Baseline to 26 weeks ]Measure of the structural brain volume as assessed by the left caudate volume.
- Change From Baseline in Cognitive Test Battery - TMT Part B [ Time Frame: Baseline to 26 weeks ]
Trail Making Test Part B was assessed by the number of seconds to complete the test (from 0 to 240 seconds).
The Trails Making Test Part B actual change from baseline at Week 26 was analysed.
|Study Start Date:||April 2012|
|Study Completion Date:||February 2014|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
|Experimental: PBT2 250mg||
250mg capsules administered orally once per day for 26 weeks
|Experimental: PBT2 100mg||
100mg capsules administered orally once per day for 26 weeks
|Placebo Comparator: Sugar pill||
Matching capsules administered orally once per day for 26 weeks
Please refer to this study by its ClinicalTrials.gov identifier: NCT01590888
|United States, California|
|University of California San Diego|
|San Diego, California, United States, 92161|
|United States, Colorado|
|Colorado Neurological Institute|
|Englewood, Colorado, United States, 80113|
|United States, Connecticut|
|University of Connecticut Health Center|
|Farmington, Connecticut, United States, 06030|
|United States, Florida|
|University of Miami|
|Miami, Florida, United States, 33136|
|United States, Maryland|
|University of Maryland School of Medicine|
|Baltimore, Maryland, United States, 21201|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21287|
|United States, Massachusetts|
|Massachusetts General Hospital East|
|Charlestown, Massachusetts, United States, 02129|
|United States, Minnesota|
|Struthers Parkinson's Center|
|Golden Valley, Minnesota, United States, 55427|
|United States, Missouri|
|St. Louis, Missouri, United States, 63110|
|United States, New York|
|Albany Medical College|
|Albany, New York, United States, 12208|
|Columbia University Medical Center|
|New York City, New York, United States, 10032|
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|United States, Tennessee|
|University of Tennessee Health Science Center|
|Memphis, Tennessee, United States, 38163|
|United States, Washington|
|Booth Gardner Parkinson's Care Center|
|Kirkland, Washington, United States, 98034|
|Australia, New South Wales|
|Sydney, New South Wales, Australia, 2145|
|Calvary Health Care Bethlehem|
|Clayton, Victoria, Australia, 3800|
|University of Melbourne Normanby Unit - St Vincents/St Georges|
|Melbourne, Victoria, Australia, 3101|
|Royal Melbourne Hospital|
|Parkville, Victoria, Australia, 3050|
|Australia, Western Australia|
|Neurodegenerative Disorders Research|
|Perth, Western Australia, Australia, 6008|
|Principal Investigator:||Ray Dorsey||Johns Hopkins University|