Huntington DiseasePhase 2Reach2HDNCT01590888

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

A Phase 2 study testing PBT2 in people with Huntington Disease, run by Prana Biotechnology Limited at 19 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 25 years and older
Conditions the study is for: Huntington Disease
What is being tested?: PBT2
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 109 participants
Where: 19 sitesin 2 countries
Study dates: Apr 2012to Feb 2014
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 25 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients who:
Provide signed informed consent in accordance with local regulations.
Have Huntington disease including clinical features of HD and a CAG repeat number ≥ 36.
Have a Total Functional Capacity between 6 and 13, inclusive.
Have cognitive impairment as demonstrated by a MoCA score of ≥ 12.
Are ≥ 25 years of age.

Show all 12Show fewer

If taking tetrabenazine, have been on a stable dose for at least 3 months.
If female, are either a) of childbearing potential and compliant in using adequate birth control or b) not of childbearing potential.
If male, is either a) of reproductive potential and compliant in using adequate birth control or b) not of reproductive potential.
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.
Are able to swallow oral capsules.
Are fluent in the English language for the administration of rating scales and have sufficient visual, hearing and motor skills to complete procedures.

Who cannot join

Patients who:
Have an allergy to PBT2 or its excipients.
Have other known primary neurodegenerative disorders associated with dementia.
Have known dementia syndromes due to non-primary CNS disease.
Have another condition that in the investigator's judgment is resulting in clinically significant cognitive impairment.
In the opinion of the investigator, have any clinically significant uncontrolled medical or psychiatric illness, including history of seizures.

Show all 10Show fewer

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.
Have a calculated creatinine clearance at Screening of <50mL/min.
Have a history of malignancy diagnosed within 2 years of Screening.
Are pregnant or lactating females.

Trial locations and contacts

19 sites in 2 countries.

Country

City, postcode or hospital

19 sites in 2 countries

United States14 sites

Albany Medical College
Albany, New York, 12208
University of Maryland School of Medicine
Baltimore, Maryland, 21201
Johns Hopkins University
Baltimore, Maryland, 21287
Massachusetts General Hospital East
Charlestown, Massachusetts, 02129
Ohio State University Medical Center
Columbus, Ohio, 43210
Colorado Neurological Institute
Englewood, Colorado, 80113
University of Connecticut Health Center
Farmington, Connecticut, 06030
Struthers Parkinson's Center
Golden Valley, Minnesota, 55427
Booth Gardner Parkinson's Care Center
Kirkland, Washington, 98034
University of Tennessee Health Science Center
Memphis, Tennessee, 38163
University of Miami
Miami, Florida, 33136
Columbia University Medical Center
New York, New York, 10032
University of California San Diego
San Diego, California, 92161
Washington University
St Louis, Missouri, 63110

Other trials in United States

Australia5 sites

Calvary Health Care Bethlehem
Clayton, Victoria, 3800
University of Melbourne Normanby Unit - St Vincents/St Georges
Melbourne, Victoria, 3101
Royal Melbourne Hospital
Parkville, Victoria, 3050
Neurodegenerative Disorders Research
Perth, Western Australia, 6008
Westmead Hospital
Sydney, New South Wales, 2145

Other trials in Australia

About this study

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

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.

Conditions: Huntington Disease
Being tested: PBT2, Placebo
Medical subject headings: Huntington Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PBT2Drug
250mg capsules administered orally once per day for 26 weeks
PBT2Drug
100mg capsules administered orally once per day for 26 weeks
PlaceboDrug
Matching capsules administered orally once per day for 26 weeks

Study groups in NCT01590888
Study group	Role	What they receive
PBT2 250mg	Experimental	Not described Receives: Drug: PBT2
PBT2 100mg	Experimental	Not described Receives: Drug: PBT2
Sugar pill	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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,
Measured: Baseline to 26 weeks

Secondary outcomes (12)

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.
Measured: Baseline to 26 weeks
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).
Measured: Baseline to 26 weeks
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.
Measured: Baseline to 26 weeks
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.
Measured: Baseline to 26 weeks
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.
Measured: Baseline to 26 weeks
Change From Baseline in Blood Biomarkers
Biomarkers assessed primarily with mutant huntingtin protein, normalised to lysate protein concentrations, as a change from baseline.
Measured: Baseline to 26 weeks
Change From Baseline in Brain Function (MRI)
Measure of whole brain iron concentrations.
Measured: Baseline to 26 weeks
Change From Baseline in Blood Biomarkers
Biomarkers assessed primarily with soluble huntingtin protein, normalised to lysate protein concentrations, as a change from baseline.
Measured: Baseline to 26 weeks
Change From Baseline in Blood Biomarkers - Selenium
Biomarkers assessed primarily with plasma selenium as a change from baseline.
Measured: Baseline to 26 weeks
Change From Baseline in Urine Biomarkers
Biomarkers assessed primarily with 8-hydroxy-2'-deoxyguanosine, normalised to creatinine concentrations, as a change from baseline.
Measured: Baseline to 26 weeks
Change From Baseline in Brain Function (MRI)
Measure of the structural brain volume as assessed by the left caudate volume.
Measured: Baseline to 26 weeks
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.
Measured: Baseline to 26 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2012Feb 2014

First posted3 May 2012 (estimated)
Study startApr 2012
Primary completionJul 2013
Study completionFeb 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Huntington DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 109 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01590888
Sponsor's protocol ID: PBT2-203
Acronym: Reach2HD
Status last verified: Jun 2016
First submitted: 18 Apr 2012
Last updated: 18 Jul 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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.
PubMed 18672400
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.
PubMed 20164561
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.
PubMed 25467848
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.
PubMed 25063332

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Huntington Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01590888
Acronym / sponsor ID: Reach2HD / PBT2-203
Conditions: Huntington Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 109 participants (actual)
Lead sponsor: Prana Biotechnology LimitedIndustry (pharma, biotech, devices)
Study start: Apr 2012
Primary completion: Jul 2013 (actual)
Study completion: Feb 2014 (actual)
First posted: 3 May 2012 (estimated)
Results: Posted 18 Jul 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
PBT2 250mg	Experimental	Drug: PBT2
PBT2 100mg	Experimental	Drug: PBT2
Sugar pill	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 25 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Patients who:

Key exclusion criteria (10 listed)

Patients who:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PBT2250mg capsules administered orally once per day for 26 weeks	Drug	PBT2 250mg
PBT2100mg capsules administered orally once per day for 26 weeks	Drug	PBT2 100mg
PlaceboMatching capsules administered orally once per day for 26 weeks	Drug	Sugar pill

Primary outcome

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,

12 secondary outcomes

Change From Baseline in Cognitive Test Battery - Composite z Scores
Time frame: Baseline to 26 weeks
Change From Baseline in Motor Function
Time frame: Baseline to 26 weeks
Change From Baseline in Functional Abilities
Time frame: Baseline to 26 weeks
Change From Baseline in Behaviour
Time frame: Baseline to 26 weeks
Change From Baseline in Investigator Global Assessments by Efficacy Index
Time frame: Baseline to 26 weeks
Change From Baseline in Blood Biomarkers
Time frame: Baseline to 26 weeks
Change From Baseline in Brain Function (MRI)
Time frame: Baseline to 26 weeks
Change From Baseline in Blood Biomarkers
Time frame: Baseline to 26 weeks
Change From Baseline in Blood Biomarkers - Selenium
Time frame: Baseline to 26 weeks
Change From Baseline in Urine Biomarkers
Time frame: Baseline to 26 weeks
Change From Baseline in Brain Function (MRI)
Time frame: Baseline to 26 weeks
Change From Baseline in Cognitive Test Battery - TMT Part B
Time frame: Baseline to 26 weeks

Results and safety

Results posted to the registry on 18 Jul 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PBT2 250mg	36	32
PBT2 100mg	38	38
Sugar Pill	35	34

Primary outcome: Safety and Tolerability of PBT2 in Patients With HD

Time frame: Baseline to 26 weeks. Number. Unit: participants

Measure	PBT2 250mg n = 36	PBT2 100mg n = 38	Sugar Pill n = 35
Value	32	30	28

Population analysed: Safety population as defined as all participants who received at least one dose of study drug.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Reported AEs from time of consent to end of study (Week 30 or 4 weeks post cessation of study drug).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
PBT2 250mg	5 of 36 (13.9%)	3 of 36 (8.3%)	Not reported
PBT2 100mg	2 of 38 (5.3%)	3 of 38 (7.9%)	Not reported
Sugar Pill	1 of 35 (2.9%)	2 of 35 (5.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 18672400Lannfelt 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: PubMed 20164561Faux 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.
Derived from this study: PubMed 25467848Huntington 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.
Derived from this study: PubMed 25063332Cherny 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.

Related trials for Huntington Disease

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RecruitingPhase 3
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ray Dorsey principal investigator

Johns Hopkins University

19 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PBT2 in people with Huntington Disease, run by Prana Biotechnology Limited at 19 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability of PBT2 in Patients With HD (time frame: Baseline to 26 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01590888, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2016.