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Effect of PBT2 in Patients With Early to Mid Stage Huntington Disease (Reach2HD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Prana Biotechnology Limited
ClinicalTrials.gov Identifier:
NCT01590888
First received: April 18, 2012
Last updated: June 7, 2016
Last verified: June 2016
  Purpose

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.


Condition Intervention Phase
Huntington Disease
Drug: PBT2
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Prana Biotechnology Limited:

Primary Outcome Measures:
  • Safety and Tolerability of PBT2 in Patients With HD [ Time Frame: Baseline to 26 weeks ] [ Designated as safety issue: Yes ]
    As measured by the total number of participants in each dose group who reported at least one adverse events during the study,


Secondary Outcome Measures:
  • Change From Baseline in Cognitive Test Battery - Composite z Scores [ Time Frame: Baseline to 26 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Measure of whole brain iron concentrations.

  • Change From Baseline in Blood Biomarkers [ Time Frame: Baseline to 26 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Biomarkers assessed primarily with plasma selenium as a change from baseline.

  • Change From Baseline in Urine Biomarkers [ Time Frame: Baseline to 26 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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.



Enrollment: 109
Study Start Date: April 2012
Study Completion Date: February 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PBT2 250mg Drug: PBT2
250mg capsules administered orally once per day for 26 weeks
Experimental: PBT2 100mg Drug: PBT2
100mg capsules administered orally once per day for 26 weeks
Placebo Comparator: Sugar pill Drug: Placebo
Matching capsules administered orally once per day for 26 weeks

  Eligibility

Ages Eligible for Study:   25 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

      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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01590888

Locations
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
Washington University
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
Westmead Hospital
Sydney, New South Wales, Australia, 2145
Australia, Victoria
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
Sponsors and Collaborators
Prana Biotechnology Limited
Investigators
Principal Investigator: Ray Dorsey Johns Hopkins University
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prana Biotechnology Limited
ClinicalTrials.gov Identifier: NCT01590888     History of Changes
Other Study ID Numbers: PBT2-203 
Study First Received: April 18, 2012
Results First Received: November 17, 2015
Last Updated: June 7, 2016
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on September 23, 2016