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

Huntington Disease Clinical Trial

— Reach2HD  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01590888
• Other study ID #: PBT2-203
• Status: Completed
• Phase: Phase 2
• First received: April 18, 2012
• Last updated: February 9, 2014
• Start date: April 2012
• Est. completion date: February 2014

Study information

• Verified date: February 2014
• Source: Prana Biotechnology Limited
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical 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. 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 more recently, 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. Based on these results, this clinical trial is investigating whether the drug will have similar effects with HD patients.

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 six months 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: February 2014
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 25 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Huntington Disease

Intervention

Drug:
• PBT2
250mg capsules administered orally once per day for 26 weeks
• PBT2
100mg capsules administered orally once per day for 26 weeks
• Placebo
Matching capsules administered orally once per day for 26 weeks

Locations

Country	Name	City	State
Australia	Monash University	Clayton	Victoria
Australia	University of Melbourne Normanby Unit	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Neurodegenerative Disorders Research	Perth	Western Australia
Australia	Westmead Hospital	Sydney	New South Wales
United States	Albany Medical College	Albany	New York
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	Massachusetts General Hospital East	Charlestown	Massachusetts
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Colorado Neurological Institute	Englewood	Colorado
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	Struthers Parkinson's Center	Golden Valley	Minnesota
United States	Booth Gardner Parkinson's Care Center	Kirkland	Washington
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	University of Miami	Miami	Florida
United States	Columbia University Medical Center	New York City	New York
United States	University of California San Diego	San Diego	California
United States	Washington University	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Prana Biotechnology Limited

Countries where clinical trial is conducted

United States,  Australia, 

References & Publications (2)

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. — View 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. Erratum in: Lancet Neurol. 2009 Nov;8(11):981. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability of PBT2 in patients with HD by measuring Frequency of Adverse Events.		26 weeks	Yes
Secondary	Change from Baseline in Cognitive Test Battery		12 and 26 weeks	No
Secondary	Change from Baseline in Motor Function		12 and 26 weeks	No
Secondary	Change from Baseline in Functional Abilities		12 and 26 weeks	No
Secondary	Change from Baseline in Behaviour		12 and 26 weeks	No
Secondary	Change from Baseline in Subject and Investigator Global Assessments		12 and 26 weeks	No
Secondary	Change from Baseline in plasma and urine Biomarkers		12 and 26 weeks	No
Secondary	Change from Baseline in Brain Volumes and Function (MRI)		12 and 26 weeks	No