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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01590888




Registration number
NCT01590888
Ethics application status
Date submitted
18/04/2012
Date registered
3/05/2012
Date last updated
18/07/2016

Titles & IDs
Public title
Effect of PBT2 in Patients With Early to Mid Stage Huntington Disease
Scientific 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
Secondary ID [1] 0 0
PBT2-203
Universal Trial Number (UTN)
Trial acronym
Reach2HD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Huntington Disease 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PBT2
Treatment: Drugs - PBT2
Treatment: Drugs - Placebo

Experimental: PBT2 250mg -

Experimental: PBT2 100mg -

Placebo Comparator: Sugar pill -


Treatment: Drugs: PBT2
250mg capsules administered orally once per day for 26 weeks

Treatment: Drugs: PBT2
100mg capsules administered orally once per day for 26 weeks

Treatment: Drugs: Placebo
Matching capsules administered orally once per day for 26 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and Tolerability of PBT2 in Patients With HD - As measured by the total number of participants in each dose group who reported at least one adverse events during the study,
Timepoint [1] 0 0
Baseline to 26 weeks
Secondary outcome [1] 0 0
Change From Baseline in Cognitive Test Battery - Composite z Scores - 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.
Timepoint [1] 0 0
Baseline to 26 weeks
Secondary outcome [2] 0 0
Change From Baseline in Motor Function - 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).
Timepoint [2] 0 0
Baseline to 26 weeks
Secondary outcome [3] 0 0
Change From Baseline in Functional Abilities - 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.
Timepoint [3] 0 0
Baseline to 26 weeks
Secondary outcome [4] 0 0
Change From Baseline in Behaviour - 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.
Timepoint [4] 0 0
Baseline to 26 weeks
Secondary outcome [5] 0 0
Change From Baseline in Investigator Global Assessments by Efficacy Index - 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.
Timepoint [5] 0 0
Baseline to 26 weeks
Secondary outcome [6] 0 0
Change From Baseline in Blood Biomarkers - Biomarkers assessed primarily with mutant huntingtin protein, normalised to lysate protein concentrations, as a change from baseline.
Timepoint [6] 0 0
Baseline to 26 weeks
Secondary outcome [7] 0 0
Change From Baseline in Brain Function (MRI) - Measure of whole brain iron concentrations.
Timepoint [7] 0 0
Baseline to 26 weeks
Secondary outcome [8] 0 0
Change From Baseline in Blood Biomarkers - Biomarkers assessed primarily with soluble huntingtin protein, normalised to lysate protein concentrations, as a change from baseline.
Timepoint [8] 0 0
Baseline to 26 weeks
Secondary outcome [9] 0 0
Change From Baseline in Blood Biomarkers - Selenium - Biomarkers assessed primarily with plasma selenium as a change from baseline.
Timepoint [9] 0 0
Baseline to 26 weeks
Secondary outcome [10] 0 0
Change From Baseline in Urine Biomarkers - Biomarkers assessed primarily with 8-hydroxy-2'-deoxyguanosine, normalised to creatinine concentrations, as a change from baseline.
Timepoint [10] 0 0
Baseline to 26 weeks
Secondary outcome [11] 0 0
Change From Baseline in Brain Function (MRI) - Measure of the structural brain volume as assessed by the left caudate volume.
Timepoint [11] 0 0
Baseline to 26 weeks
Secondary outcome [12] 0 0
Change From Baseline in Cognitive Test Battery - TMT Part B - 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.
Timepoint [12] 0 0
Baseline to 26 weeks

Eligibility
Key inclusion criteria
- Patients who:

1. Provide signed informed consent in accordance with local regulations.

2. Have Huntington disease including clinical features of HD and a CAG repeat number
= 36.

3. Have a Total Functional Capacity between 6 and 13, inclusive.

4. Have cognitive impairment as demonstrated by a MoCA score of = 12.

5. Are = 25 years of age.

6. If taking tetrabenazine, have been on a stable dose for at least 3 months.

7. If female, are either a) of childbearing potential and compliant in using
adequate birth control or b) not of childbearing potential.

8. If male, is either a) of reproductive potential and compliant in using adequate
birth control or b) not of reproductive potential.

9. Have a study partner who is willing to provide consent and spends on average at
least two hours a day for at least four days a week with the patient, is fluent
in the English language, and who agrees to attend certain study visits and
provide accurate information about the patient.

10. Are able to swallow oral capsules.

11. Are fluent in the English language for the administration of rating scales and
have sufficient visual, hearing and motor skills to complete procedures.
Minimum age
25 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients who:

1. Have an allergy to PBT2 or its excipients.

2. Have other known primary neurodegenerative disorders associated with dementia.

3. Have known dementia syndromes due to non-primary CNS disease.

4. Have another condition that in the investigator's judgment is resulting in
clinically significant cognitive impairment.

5. In the opinion of the investigator, have any clinically significant uncontrolled
medical or psychiatric illness, including history of seizures.

6. Have clinically significant cardiovascular, hepatic, renal, pulmonary, metabolic
or endocrine disease that, in the opinion of the investigator, would interfere
with an individual's participation in the study.

7. Have a calculated creatinine clearance at Screening of <50mL/min.

8. Have a history of malignancy diagnosed within 2 years of Screening.

9. Are pregnant or lactating females.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Westmead Hospital - Sydney
Recruitment hospital [2] 0 0
Calvary Health Care Bethlehem - Clayton
Recruitment hospital [3] 0 0
University of Melbourne Normanby Unit - St Vincents/St Georges - Melbourne
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [5] 0 0
Neurodegenerative Disorders Research - Perth
Recruitment postcode(s) [1] 0 0
2145 - Sydney
Recruitment postcode(s) [2] 0 0
3800 - Clayton
Recruitment postcode(s) [3] 0 0
3101 - Melbourne
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment postcode(s) [5] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Prana Biotechnology Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT01590888
Trial related presentations / publications
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. Erratum in: Lancet Neurol. 2009 Nov;8(11):981.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Ray Dorsey
Address 0 0
Johns Hopkins University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications