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

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

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.

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.