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Trial registered on ANZCTR


Trial ID
ACTRN12613000777796
Ethics application status
Approved
Date submitted
10/07/2013
Date registered
11/07/2013
Date last updated
31/03/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase II Extension study to assess the safety and tolerability of PBT2 and its effect on amyloid levels in the brains of patients with prodromal or mild Alzheimer's disease.
Scientific title
An Open Label Extension Study to Assess the Safety and Tolerability of PBT2, and its Effect on Amyloid Deposition in the Brains of Patients with Prodromal or Mild Alzheimer's Disease.
Secondary ID [1] 282731 0
Nil
Universal Trial Number (UTN)
Trial acronym
PBT2-204-Ext
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prodromal Alzheimer's disease or mild Alzheimer's disease 289465 0
Condition category
Condition code
Mental Health 289777 289777 0 0
Other mental health disorders
Neurological 289778 289778 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
PBT2 is supplied as 250mg immediate-release capsules. The dose for this study is 250mg / day ie. one capsule is to be taken orally, once a day for 52 weeks duration.
Information on compliance will be collected via a Diary Card and accountability of drug returns. It is also the role of the Study Partner to over-see the daily taking of study drug.
Intervention code [1] 287394 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289861 0
To evaluate the safety and tolerability of PBT2 after 52 weeks of treatment as measured by capture of vital signs, physical examination, neurological examination, ECG, eye examination, blood haematology and biochemistry, urinalysis and recording of adverse events.
Possible side effects include tiredness, headache, dizziness, nasopharyingitis and drowsiness.
Timepoint [1] 289861 0
Baseline, 4, 8, 13, 26, 39 and 52 weeks after commencement of treatment with PBT2 and 4 weeks after cessation of treatment with PBT2
Primary outcome [2] 289862 0
To evaluate the effect of PBT2 on brain amyloid levels after 52 weeks of treatment as measured by Carbon 11-Pittsburgh Imaging Compound-B (PiB) Positron Emission Tomography (PET) imaging.
Timepoint [2] 289862 0
52 weeks after commencement of treatment with PBT2.
Secondary outcome [1] 303405 0
To evaluate the effect of PBT2 on brain metabolic activity after 52 weeks as measured by Fluorine 18 labelled Fluorodeoxyglucose (FDG) PET imaging.
Timepoint [1] 303405 0
52 weeks after commencement of treatment with PBT2.
Secondary outcome [2] 303406 0
To evaluate the effect of PBT2 on brain volumes after 52 weeks as assessed by Magnetic Resonance Imaging (MRI) to measure the cortical grey matter volume, hippocampal volume and ventricular volume.
Timepoint [2] 303406 0
52 weeks after commencement of treatment with PBT2.
Secondary outcome [3] 303407 0
To evaluate the effect of PBT2 on cognition after 52 weeks as measured by a Neuropsychological Test Battery (NTB) questionnaires and the Mini-mental State Examination (MMSE) questionnaire.
Timepoint [3] 303407 0
Baseline, 26 and 52 weeks after commencement of treatment with PBT2.
Secondary outcome [4] 303408 0
To evaluate the effect of PBT2 on functional ability after 52 weeks as measured by the Alzheimer's disease Cooperative Study-Activities of Daily Living-23 (ADCS-ADL-23) questionnaire
Timepoint [4] 303408 0
Baseline and 52 weeks after commencement of treatment with PBT2.
Secondary outcome [5] 303409 0
To evaluate the effect of PBT2 on Alzheimer's disease blood biomarkers.
Timepoint [5] 303409 0
Baseline, 13, 26, 39 and 52 weeks after commencement of treatment with PBT2 and 1 month after cessation of treatment.

Eligibility
Key inclusion criteria
1. Patients who have completed Visit 10 (Week 52) of the PBT2-204 (IMAGINE) clinical trial [ACTRN12611001008910].
Minimum age
55 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Allergy to PBT2 or its excipients (microcrystalline cellulose, pregelatinised starch, colloidal silicon dioxide, povidone K29/32 and sodium stearyl fumurate).
2. Have developed any clinically significant uncontrolled medical, ocular or psychiatric illness during PBT2-204.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All participants enrolled into this Extension study will receive PBT2, regardless of their treatment allocation in the IMAGINE (PBT2-204) clinical trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1207 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment hospital [2] 1209 0
Delmont Private Hospital - Glen Iris
Recruitment hospital [3] 1210 0
Geelong Private Hospital - Geelong
Recruitment postcode(s) [1] 7069 0
3081 - Heidelberg West
Recruitment postcode(s) [2] 7071 0
3146 - Glen Iris
Recruitment postcode(s) [3] 7072 0
3220 - Geelong

Funding & Sponsors
Funding source category [1] 287559 0
Commercial sector/Industry
Name [1] 287559 0
Prana Biotechnology Ltd
Address [1] 287559 0
Level 2, 369 Royal Parade
Parkville VIC 3052
Country [1] 287559 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Prana Biotechnology Ltd
Address
Level 2, 369 Royal Parade
Parkville VIC 3052
Country
Australia
Secondary sponsor category [1] 286310 0
None
Name [1] 286310 0
Address [1] 286310 0
Country [1] 286310 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289536 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 289536 0
145 Studley Road
Heidelberg VIC 3084
Ethics committee country [1] 289536 0
Australia
Date submitted for ethics approval [1] 289536 0
03/06/2013
Approval date [1] 289536 0
02/07/2013
Ethics approval number [1] 289536 0
HREC/13/Austin/54

Summary
Brief summary
This is a Phase II Extension study to examine the safety, tolerability and effect of 52 weeks treatment with PBT2 in patients with prodromal or mild Alzheimer's disease (AD). The primary objectives are to examine the safety and tolerability and the effect of PBT2 on the amount of amyloid in patients brains after 52 weeks of treatment when measured by a particular type of brain scan, PiB-Positron Emission Tomography (PET). The effects of PBT2 on brain volume, brain metabolic activity, blood biomarkers of AD and cognition plus functional abilities will also be investigated.
Trial website
Trial related presentations / publications
Public notes
Please note that participation in this Extension study is only open to patients who have participated in the PBT2-204 clinical trial. No new patients will be entered.

Contacts
Principal investigator
Name 41026 0
A/Prof Michael Woodward
Address 41026 0
Medical & Cognitive Research Unit Heidelberg Repatriation Hospital 300 Waterdale Road Heidelberg West, VIC 3081
Country 41026 0
Australia
Phone 41026 0
+61 (0)3 9496 2852
Fax 41026 0
Email 41026 0
michael.woodward@austin.org.au
Contact person for public queries
Name 41027 0
Ms Dianne Angus
Address 41027 0
Prana Biotechnology Limited
Level 2, 369 Royal Parade
Parkville 3052 Victoria
Country 41027 0
Australia
Phone 41027 0
+61 (0)3 9349 4906
Fax 41027 0
+61 (0)3 9348 0377
Email 41027 0
info@pranabio.com
Contact person for scientific queries
Name 41028 0
Ms Dianne Angus
Address 41028 0
Prana Biotechnology Limited
Level 2, 369 Royal Parade
Parkville 3052 Victoria
Country 41028 0
Australia
Phone 41028 0
+61 (0)3 9349 4906
Fax 41028 0
+61 (0)3 9348 0377
Email 41028 0
info@pranabio.com