Clinical trial NCT01590888: Effect of PBT2 in Patients With Early to Mid Stage Huntington Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Huntington Disease
Lead sponsor: Pranabio
Sponsor class: UNKNOWN
First posted: 2012-05-03
Enrollment: 109
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Safety and Tolerability of PBT2 in Patients With HD
timeFrame: Baseline to 26 weeks
Secondary outcomes:
measure: Change From Baseline in Cognitive Test Battery - Composite z Scores
timeFrame: Baseline to 26 weeks
measure: Change From Baseline in Motor Function
timeFrame: Baseline to 26 weeks
measure: Change From Baseline in Functional Abilities
timeFrame: Baseline to 26 weeks
measure: Change From Baseline in Behaviour
timeFrame: Baseline to 26 weeks
measure: Change From Baseline in Investigator Global Assessments by Efficacy Index
timeFrame: Baseline to 26 weeks
measure: Change From Baseline in Blood Biomarkers
timeFrame: Baseline to 26 weeks
measure: Change From Baseline in Brain Function (MRI)
timeFrame: Baseline to 26 weeks
measure: Change From Baseline in Blood Biomarkers
timeFrame: Baseline to 26 weeks
measure: Change From Baseline in Blood Biomarkers - Selenium
timeFrame: Baseline to 26 weeks
measure: Change From Baseline in Urine Biomarkers
timeFrame: Baseline to 26 weeks
measure: Change From Baseline in Brain Function (MRI)
timeFrame: Baseline to 26 weeks
measure: Change From Baseline in Cognitive Test Battery - TMT Part B
timeFrame: Baseline to 26 weeks
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Englewood
country: United States
facility: Colorado Neurological Institute
state: Colorado
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Charlestown
country: United States
facility: Massachusetts General Hospital East
state: Massachusetts
city: Golden Valley
country: United States
facility: Struthers Parkinson's Center
state: Minnesota
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: New York City
country: United States
facility: Columbia University Medical Center
state: New York
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Memphis
country: United States
facility: University of Tennessee Health Science Center
state: Tennessee
city: Kirkland
country: United States
facility: Booth Gardner Parkinson's Care Center
state: Washington
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Clayton
country: Australia
facility: Calvary Health Care Bethlehem
state: Victoria
city: Melbourne
country: Australia
facility: University of Melbourne Normanby Unit - St Vincents/St Georges
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Perth
country: Australia
facility: Neurodegenerative Disorders Research
state: Western Australia
Study officials:
affiliation: Johns Hopkins University
name: Ray Dorsey
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.