ANZCTR

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Request Number:
Current Page:	Review

Trial from ANZCTR

Trial ID	ACTRN12611001008910
Trial Status:	Registered
Date Submitted:	17/09/2011
Date Registered:	20/09/2011
	Prospectively registered

Page 1

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.

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Reason:

Study title in 'Participant- Intervention- Comparator- Outcome (PICO)' format

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.

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Secondary ID [1]

Nil

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UTN

U1111-1124-2486

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Trial acronym

PBT2-204 / IMAGINE

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Page 2

Health condition(s) or problem(s) studied:

Prodromal Alzheimer's disease or mild Alzheimer's disease

Condition category:

Condition code:

Mental Health

Other mental health disorders

Neurological

Dementias

Page 3

Descriptions 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.

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Intervention Code:

Treatment: drugs

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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.

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Control group

Placebo

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Page 4

Primary Outcome:

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.

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Timepoint:

Baseline, 26 and 52 weeks after commencement of treatment with PBT2/placebo

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Secondary Outcome:

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).

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Timepoint:

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

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Secondary Outcome:

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.

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Timepoint:

Baseline and 52 weeks after commencement of of treatment withPBT2/placebo

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Secondary Outcome:

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.

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Timepoint:

Baseline and 52 weeks after commencement of of treatment withPBT2/placebo

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Secondary Outcome:

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.

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Timepoint:

Baseline, 13, 26, 39 and 52 weeks after commencement of treatment with PBT2/placebo

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Secondary Outcome:

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

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Timepoint:

Baseline and 52 weeks after commencement of treatment with PBT2/placebo

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Page 5

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

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Minimum age

55 Years

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Maximum age

No limit

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Gender

Both males and females

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Healthy volunteers?

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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)

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Page 6

Study type

Interventional

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Purpose of the study

Treatment

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Allocation to intervention

Randomised controlled trial

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Describe the 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.

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Describe the 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.

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Masking / blinding

Blinded (masking used)

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Who is / are masked / blinded (choose all that apply)

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

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Assignment

Parallel

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Other design features

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Type of endpoint(s)

Safety/efficacy

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Statistical Methods/Analysis

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Page 7

Phase

Phase 2

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Anticipated date of first participant enrolment

17/10/2011

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Date of first participant enrolment

2/03/2012

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Anticipated date last participant recruited/enrolled

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Actual date last participant recruited/enrolled

28/11/2012

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Target sample size

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Recruitment status

Closed: follow-up complete

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Recruitment in Australia

Recruitment state(s)

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Hospital:

Austin Health - Heidelberg Repatriation Hospital - Heidelberg West

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Hospital:

Caulfield Hospital - Caulfield

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Hospital:

Delmont Private Hospital - Glen Iris

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Hospital:

Royal Melbourne Hospital - City campus - Parkville

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Hospital:

Barwon Health - Geelong Hospital campus - Geelong

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Postcode:

3081

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Postcode:

3162

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Postcode:

3146

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Postcode:

3050 - Royal Melbourne Hospital

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Postcode:

3220 - Geelong

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Recruitment outside Australia

Page 8

Funding Source:

Charities/Societies/Foundations

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Name:

Alzheimer's Drug Discovery Foundation (ADDF)

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Address:

57 West 57th Street,
Suite 904,
NEW YORK,
NY 10019 New York

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Country:

United States of America

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Primary Sponsor

Commercial sector/Industry

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Name:

Prana Biotechnology Limited

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Address:

Level 2, 369 Royal Parade
Parkville 3052
Victoria

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Australia

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Secondary Sponsor:

None

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Page 9

Has the study received approval from at least one Ethics Committee?

Yes

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Ethics Committee name:

Austin Health Human Research Ethics Committee

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Address:

Henry Buck Building
Austin Hospital
145 Studley Road
Heidelberg 3084
Victoria

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Country:

Australia

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Approval Date:

17/11/2011

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Submitted Date:

17/08/2011

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HREC:

HREC/11/Austin/42

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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.

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Reason:

Trial website

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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.

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Public Notes

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Page 10

Principal Investigator

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A/Prof

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Name:

Associate Professor Michael Woodward

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Address:

Medical & Cognitive Research Unit Heidelberg Repatriation Hospital 300 Waterdale Road Heidelberg West, VIC 3081

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Country:

Australia

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Tel:

+61 (0)3 9496 2852

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Email:

michael.woodward@austin.org.au

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Contact person for public queries

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Name:

Dianne Angus

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Address:

Prana Biotechnology Limited Level 2, 369 Royal Parade Parkville 3052 Victoria

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Australia

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Tel:

+61 (0)3 9349 4906

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+61 (0)3 9348 0377

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Email:

info@pranabio.com

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Contact person for scientific queries

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Name:

Dianne Angus

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Address:

Prana Biotechnology Limited Level 2, 369 Royal Parade Parkville 3052 Victoria

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Australia

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+61 (0)3 9349 4906

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+61 (0)3 9348 0377

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info@pranabio.com

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Australia

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Addition Cancer fields

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