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

NCT01590888 | Completed Phase 2 Results DMC

• 1 other identifier: PBT2-203
• Study Type: interventional
• Target: 109
• Locations: 2 countries
• Sites: 19

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.

Conditions

Huntington Disease

Outcome Measures

Primary Outcomes (1)

• 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,

  Baseline to 26 weeks

Secondary Outcomes (12)

• Change From Baseline in Cognitive Test Battery - Composite z Scores

  Baseline to 26 weeks

• Change From Baseline in Motor Function

  Baseline to 26 weeks

• Change From Baseline in Functional Abilities

  Baseline to 26 weeks

• Change From Baseline in Behaviour

  Baseline to 26 weeks

• Change From Baseline in Investigator Global Assessments by Efficacy Index

  Baseline to 26 weeks

Study Arms (3)

PBT2 250mg

EXPERIMENTAL

Drug: PBT2

PBT2 100mg

EXPERIMENTAL

Drug: PBT2

Sugar pill

PLACEBO COMPARATOR

Drug: Placebo

Interventions

PBT2 DRUG

250mg capsules administered orally once per day for 26 weeks

PBT2 250mg

Placebo DRUG

Matching capsules administered orally once per day for 26 weeks

Sugar pill

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Prana Biotechnology Limited: lead

Study Sites (19)

University of California San Diego

San Diego, California, 92161, United States

Location

Colorado Neurological Institute

Englewood, Colorado, 80113, United States

Location

University of Connecticut Health Center

Farmington, Connecticut, 06030, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital East

Charlestown, Massachusetts, 02129, United States

Location

Struthers Parkinson's Center

Golden Valley, Minnesota, 55427, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

University of Tennessee Health Science Center

Memphis, Tennessee, 38163, United States

Location

Booth Gardner Parkinson's Care Center

Kirkland, Washington, 98034, United States

Location

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

Calvary Health Care Bethlehem

Clayton, Victoria, 3800, Australia

Location

University of Melbourne Normanby Unit - St Vincents/St Georges

Melbourne, Victoria, 3101, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Neurodegenerative Disorders Research

Perth, Western Australia, 6008, Australia

Location

Related Publications (4)

• 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.

  PMID: 18672400 BACKGROUND

• 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.

  PMID: 20164561 BACKGROUND

• 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.

  PMID: 25467848 DERIVED

• 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.

  PMID: 25063332 DERIVED

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Dr Caroline Herd
• Organization: Prana Biotechnology

info@pranabio.com

+61393494906

Study Officials

• Ray Dorsey

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2012
• First Posted: May 3, 2012
• Study Start: April 1, 2012
• Primary Completion: July 1, 2013
• Study Completion: February 1, 2014
• Last Updated: July 18, 2016
• Results First Posted: July 18, 2016

Record last verified: 2016-06

Locations

US (14); AU (5)