Trial registered on ANZCTR


Trial ID
ACTRN12611001008910
Ethics application status
Approved
Date submitted
17/09/2011
Date registered
20/09/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase II clinical trial 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
A Randomised, Double-Blind, Placebo Controlled 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] 262995 0
Nil
Universal Trial Number (UTN)
U1111-1124-2486
Trial acronym
PBT2-204 / IMAGINE

Health condition
Health condition(s) or problem(s) studied:
Prodromal Alzheimer's disease or mild Alzheimer's disease 270699 0
Condition category
Condition code
Mental Health 270873 270873 0 0
Other mental health disorders
Neurological 271010 271010 0 0
Dementias

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.
Intervention code [1] 269318 0
Treatment: drugs
Comparator / control treatment
Placebo is supplied as identical looking, immediate-release capsules. One capsule is to be taken orally, once a day for 52 weeks duration.
Control group
Placebo

Outcomes
Primary outcome [1] 279555 0
To evaluate the effect of PBT2 compared to placebo 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 [1] 279555 0
Baseline, 26 and 52 weeks after commencement of treatment with PBT2/placebo
Secondary outcome [1] 287893 0
To evaluate the safety and tolerability of PBT2 compared to placebo as measured by capture of vital signs, physical examination, neurological examination, ECG, eye examination, blood haematology and biochemistry, urinalysis and recording of adverse events.
From previous clinical trials, the most commonly reported side effects that were possibly related to PBT2 were fatigue (tiredness), headache, dizziness, nasopharyngitis (swollen blocked nose), and somnolence (drowsiness). Less common side-effects possibly related to PBT2 were diarrhoea, back pain, nausea and pharyngolaryngeal (throat) pain. It is possible that a rare side effect may be dissociation (a feeling of disconnecting from one's thoughts, feelings, memories or self).
Timepoint [1] 287893 0
Baseline, 4, 8, 13, 19, 26, 33, 39, 45 and 52 weeks after commencement of treatment with PBT2/placebo and 4 weeks after cessation of treatment with PBT2/placebo
Secondary outcome [2] 287894 0
To evaluate the effect of PBT2 compared to placebo on brain metabolic activity after 52 weeks as measured by Fluorine 18 labelled Fluorodeoxyglucose (FDG) PET imaging.
Timepoint [2] 287894 0
Baseline and 52 weeks after commencement of of treatment withPBT2/placebo
Secondary outcome [3] 287895 0
To evaluate the effect of PBT2 compared to placebo 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 [3] 287895 0
Baseline and 52 weeks after commencement of of treatment withPBT2/placebo
Secondary outcome [4] 287896 0
To evaluate the effect of PBT2 compared to placebo on cognition after 52 weeks as measured by a Neuropsychological Test Battery (NTB) questionnaires and the Mini-mental State Examination (MMSE) questionnaire.
Timepoint [4] 287896 0
Baseline, 13, 26, 39 and 52 weeks after commencement of treatment with PBT2/placebo
Secondary outcome [5] 287897 0
To evaluate the effect of PBT2 compared to placebo 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 [5] 287897 0
Baseline and 52 weeks after commencement of treatment with PBT2/placebo

Eligibility
Key inclusion criteria
1. Prodromal Alzheimer's disease or mild Alzheimer's disease
2. 11C-PiB-PET positive (SUVR>1.7)
3. MMSE >or= 20
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 other primary neurodegenerative disorders associated with dementia (e.g. Parkinson’s Disease Dementia, Fronto-temporal Lobe Dementia, Lewy Body Dementia or Vascular Dementia)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible participants will be entered on to the trial in sequence as their eligibility is confirmed. Participants will be allocated a unique Randomisation ID Number. Each participant will receive only PBT2 or placebo, with treatment assigned according to a Randomisation Schedule prepared by an independent statistician.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The Randomisation Schedule is generated by an independent statistician at a ratio of 2:1 ie. 2/3 participants will receive 250mg PBT2 and 1/3 participants will receive matching placebo.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy

Recruitment
Anticipated date of first participant enrolment
17/10/2011
Actual date of first participant enrolment
2/03/2012
Anticipated date last participant enrolled
Actual date last participant enrolled
28/11/2012
Anticipated date of last data collection
Actual date of last data collection
Target sample size
42
Actual sample size
Recruitment status
Completed
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 498 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment hospital [2] 499 0
Caulfield Hospital - Caulfield
Recruitment hospital [3] 500 0
Delmont Private Hospital - Glen Iris
Recruitment hospital [4] 501 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [5] 502 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment postcode(s) [1] 4456 0
3081
Recruitment postcode(s) [2] 4457 0
3162
Recruitment postcode(s) [3] 5419 0
3146
Recruitment postcode(s) [4] 6242 0
3050 - Royal Melbourne Hospital
Recruitment postcode(s) [5] 6243 0
3220 - Geelong

Funding & Sponsors
Funding source category [1] 269806 0
Charities/Societies/Foundations
Name [1] 269806 0
Alzheimer's Drug Discovery Foundation (ADDF)
Address [1] 269806 0
57 West 57th Street,
Suite 904,
NEW YORK,
NY 10019 New York
Country [1] 269806 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Prana Biotechnology Limited
Address
Level 2, 369 Royal Parade
Parkville 3052
Victoria
Country
Australia
Secondary sponsor category [1] 268841 0
None
Name [1] 268841 0
Address [1] 268841 0
Country [1] 268841 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 271769 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 271769 0
Henry Buck Building
Austin Hospital
145 Studley Road
Heidelberg 3084
Victoria
Ethics committee country [1] 271769 0
Australia
Date submitted for ethics approval [1] 271769 0
17/08/2011
Approval date [1] 271769 0
17/11/2011
Ethics approval number [1] 271769 0
HREC/11/Austin/42

Summary
Brief summary
This is a Phase II clinical trial 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 objective is to compare the effect of PBT2 vs placebo 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 safety and tolerability, brain volume, brain metabolic activity, and cognition plus functional abilities will also be investigated.
Trial website
Trial related presentations / publications
1. Adlard PA, Cherny R, Finkelstein DI et al (2008). Rapid restoration of cognition in Alzheimer’s transgenic mice with 8-Hydroxy Quinoline analogs is associated with decreased interstitial Aß. Neuron 59: 43–55.
2. Adlard PA, Bica L, White AR et al (2011). Metal ionophore treatment restores dendritic spine density and synaptic protein levels in a mouse model of Alzheimer’s Disease. PLoS ONE 6: e17669. doi:10.1371/journal.pone.0017669.
3. Faux NG, Ritchie CW, Gunn A et al (2010). PBT2 rapidly improves cognition in Alzheimer's disease: additional Phase II analyses. J Alzheimers Dis 20: 509-16.
4. Ikonomovic MD, Klunk WE, Abrahamson EE et al (2008). Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease. Brain 131: 1630-45.
5. Klunk WE, Engler H, Nordberg A et al (2004). Imaging brain amyloid in Alzheimer’s disease with Pittsburgh compound-B. Ann Neurol 55: 306-19.
6. Lannfelt L, Blennow K, Zetterberg H et al (2008). Safety, efficacy and biomarker findings of PBT2 in targeting Aß as a modifying therapy for Alzheimer's disease: a Phase IIa, double-blind, randomised, placebo-controlled trial. Lancet Neurol 7:779-86. Erratum in: Lancet Neurol (2009) 8: 981.
7. Rowe CC, Ng S, Ackermann U et al (2007). Imaging ß-amyloid burden in aging and dementia. Neurology 68: 1718-25.
Public notes

Contacts
Principal investigator
Name 33105 0
A/Prof Associate Professor Michael Woodward
Address 33105 0
Medical & Cognitive Research Unit
Heidelberg Repatriation Hospital
300 Waterdale Road
Heidelberg West, VIC 3081


Country 33105 0
Australia
Phone 33105 0
+61 (0)3 9496 2852
Fax 33105 0
Email 33105 0
michael.woodward@austin.org.au
Contact person for public queries
Name 16352 0
Ms Dianne Angus
Address 16352 0
Prana Biotechnology Limited
Level 2, 369 Royal Parade
Parkville 3052
Victoria
Country 16352 0
Australia
Phone 16352 0
+61 (0)3 9349 4906
Fax 16352 0
+61 (0)3 9348 0377
Email 16352 0
info@pranabio.com
Contact person for scientific queries
Name 7280 0
Ms Dianne Angus
Address 7280 0
Prana Biotechnology Limited
Level 2, 369 Royal Parade
Parkville 3052
Victoria
Country 7280 0
Australia
Phone 7280 0
+61 (0)3 9349 4906
Fax 7280 0
+61 (0)3 9348 0377
Email 7280 0
info@pranabio.com