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Trial registered on ANZCTR


Registration number
ACTRN12613000170729
Ethics application status
Approved
Date submitted
11/02/2013
Date registered
12/02/2013
Date last updated
12/02/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Open Label Extension Study to Evaluate the Safety, Tolerability
and Cognitive Effects of VEL015 (Sodium Selenate) in Patients
with Alzheimer’s Disease
Scientific title
Open Label Extension Study to Evaluate the Safety, Tolerability
and Cognitive Effects of VEL015 (Sodium Selenate) in Patients
with Alzheimer’s Disease
Secondary ID [1] 281932 0
Velacor002-E1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild to moderate Alzheimer's disease 288335 0
Condition category
Condition code
Neurological 288686 288686 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Sodium selenate (VEL015) 10mg oral capsules three time daily for 24 months
Intervention code [1] 286494 0
Treatment: Drugs
Comparator / control treatment
This is an open label extension study and will not utilise a comparator or control treatment
Control group
Uncontrolled

Outcomes
Primary outcome [1] 288836 0
The primary objective of the study is to assess the longer-term safety and tolerability of a
supranutritional dose of sodium selenate (VEL015) in subjects with probable Alzheimer’s
Disease (AD). Safety will be monitored by haematology, biochemistry, recording of body weight, the
assessment of adverse events and documentation of concomitant medications. Adverse events may include alopecia, fatigue, nail disorders (fingernails and toenails lifting and falling off), muscle spasms and cramps, decreased appetite, lethargy and fatigue, headache, vomiting, retching and diarrhoea.
Timepoint [1] 288836 0
Assessments at baseline (week 0), weeks 6, 12 and 24 and months 12, 18 and 24.
Primary outcome [2] 288837 0
The secondary objective of the study are to assess the effect of VEL015 on cognitive
performance as measured by ADAS-Cog, MMSE, CogState test battery and components
of the NTB (COWAT and CFT).
Timepoint [2] 288837 0
Assessments at baseline (week 0), weeks 6, 12 and 24 and months 12, 18 and 24.
Secondary outcome [1] 301096 0
To assess the magnitude of the treatment (VEL015) effect on cognitive performance (ADAS-Cog, MMSE, CogState test battery) in specific patient subgroups (exploratory; subjects treated/not treated in Velacor 002 study and subjects with MMSE greater than or equal to 20, and less than 20).
Timepoint [1] 301096 0
Assessments at baseline (week 0), weeks 6, 12 and 24 and months 12, 18 and 24.
Secondary outcome [2] 301127 0
To assess the association between biomarkers and measures of cognitive performance (exploratory). The biomarkers will include Alzheimer's disease biomarkers in the cerebrospinal fluid (A-beta 1-42, total Tau and phospho-Tau), atrophy of brain structures detected via MRI and areas of brain hypo- or hyper-metabolism detected via FDG-PET as part of the Velacor 002 study.
Timepoint [2] 301127 0
Assessments at baseline (week 0), weeks 6, 12 and 24 and months 12, 18 and 24.

Eligibility
Key inclusion criteria
1. Subject must have been randomised, treated and completed Visit 6 and/or Visit 7
of Protocol Velacor 002 (ACTRN12611001200976).
2. The Baseline (Month 0) visit must be conducted no more than 2 months after the
last scheduled visit (Visit 6 or Visit 7) for Protocol Velacor 002.
3. Females must be of non-child-bearing potential. Male subjects with female
partners of child-bearing potential should use effective contraception for the
duration of the Study and continue it for 12 weeks after cessation of IMP
administration. Women of non-childbearing potential must be either surgically
sterile (hysterectomy and/or oophorectomy) or postmenopausal at least 1 year and
must have a negative urine pregnancy test result at or within 28 days prior to the
Baseline Visit (Visit 1) .
4. Subject must be living in the community and have at least 5 contact hours per
week with a responsible carer. The carer should be capable of ensuring the
subject's compliance with the medication, be prepared to attend with the subject
for assessment and be willing to participate in completing the various assessments
throughout the period of the subject’s involvement in the Study
5. Written informed consent must be obtained from the subject or legally authorised
representative (as required by local laws and regulations), and the participant’s
carer.
Minimum age
55 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subject who has experienced persistent or unresolved side effects thought to be
possibly/probably/very likely/certainly related to Study Drug in the Velacor 002 study
and where the event is classified as either greater than or equal to Grade 3 severity or as a Serious
Adverse Event, or where the event required permanent cessation of Study Drug .
2. Subject has participated in a clinical investigation of a medication (with exception of
Velacor 002 study) or device within the 3 months prior to the Baseline Visit (Visit 1).
3. Subject who is unlikely to comply with trial visit schedule or with trial medication.
4. Subject has a known sensitivity to selenium or sodium selenate or any medicine or
vitamin containing sodium selenate or similar agents.
5. Subject has a primary, secondary or pseudodementia other than probable
Alzheimer's Disease, or has current evidence or history of neurological, psychiatric
and any other illness that could contribute to non-Alzheimer's dementia.
6. Subject has a significant medical disease, with the exception of Alzheimer’s Disease
that:
* is not adequately controlled by therapy; and/or
* in the opinion of the investigator may interfere with the patient’s ability to complete
the study or might impact on the patient’s cognitive performance.
7. Subject has significant impairment of any of the following for the age of the subject,
which may compromise safety of the subject/validity of the data:
* Renal function (i.e. estimated glomerular filtration rate (eGFR) < 30)
* Hepatic function (i.e. abnormal liver function tests greater than or equal to 2 x upper limit of normal)
* Haematological function.
8. Subject is currently taking any of the following:
* Dietary supplement containing > 26 micrograms selenium
* Carbamazepine, digoxin, phenobarbitone, phenytoin, warfarin or any other
medication that has a narrow margin between effective dose and toxic dose or
between effective dose and ineffective dose, where the subject would be at risk if
the levels were elevated or fell due to interaction with VEL015.

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)
This is an open label extension study to the Velacor 002 study. Patients must have previously participated in the Velacor 002 study to be eligible for this study. All patients enrolled will receive treatment with 10mg sodium selenate (VEL015) three times daily
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Study is not randomised
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
Patients recruited to this ‘extension’ protocol are ‘self-selecting’ (including only patients
who satisfactorily complete the main study) and therefore the non-randomised,
uncontrolled nature of the investigation and the potential biasing influences contributing
to any statistical analysis are recognised.
All patients will primarily be included and analysed as a single treated group (VEL015 10
mg tds) according to the treatment received in the extension and not in the main study.
All analyses will involve statistical hypothesis testing or modelling. Emphasis will be
placed on point estimates and 95% confidence intervals of the treatment effect rather
than p values. All analyses are considered exploratory and any conclusions will be
viewed cautiously. However, the study will contribute to knowledge of the ‘disease
modifying’ potential and safety profile of the compound.
No interim analyses will be performed and the analyses performed at the end of the
study reporting p values will use a 5% (0.05) (two-sided) significance level. No
adjustment for multiple testing will be made.

Recruitment
Recruitment status
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] 564 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 565 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [3] 566 0
Caulfield Hospital - Caulfield

Funding & Sponsors
Funding source category [1] 286716 0
Commercial sector/Industry
Name [1] 286716 0
Velacor Therapeutics Pty Ltd
Address [1] 286716 0
Level 2, 88 Collins Street
Melbourne, 3000
Victoria
Country [1] 286716 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Velacor Therapeutics Pty Ltd
Address
Level 2, 88 Collins Street
Melbourne, 3000
Victoria
Country
Australia
Secondary sponsor category [1] 285490 0
None
Name [1] 285490 0
Address [1] 285490 0
Country [1] 285490 0

Ethics approval
Ethics application status
Approved

Summary
Brief summary
Open Label Extension Study to Evaluate the Safety, Tolerability
and Cognitive Effects of VEL015 (Sodium Selenate) in Patients
with Alzheimer’s Disease
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 37034 0
Prof Terence O'Brien
Address 37034 0
The Royal Melbourne Hospital
Parkville, Vic 3050
Country 37034 0
Australia
Phone 37034 0
+61 3 9342 7722
Fax 37034 0
+61 3 9342 8628
Email 37034 0
obrientj@unimelb.edu.au
Contact person for public queries
Name 37035 0
Mr Darren Germaine
Address 37035 0
The Royal Melbourne Hospital
Parkville, Vic 3050
Country 37035 0
Australia
Phone 37035 0
+61 3 9342 7879
Fax 37035 0
Email 37035 0
Darren.Germaine@mh.org.au
Contact person for scientific queries
Name 37036 0
Mr Darren Germaine
Address 37036 0
The Royal Melbourne Hospital
Parkville, Vic 3050
Country 37036 0
Australia
Phone 37036 0
+61 3 9342 7879
Fax 37036 0
Email 37036 0
Darren.Germaine@mh.org.au

No information has been provided regarding IPD availability
Summary results
No Results