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Trial registered on ANZCTR


Trial ID
ACTRN12613001351707
Ethics application status
Approved
Date submitted
17/10/2013
Date registered
10/12/2013
Date last updated
20/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of low dose everolimus and/or BEZ235 on vaccine response in the elderly
Scientific title
A multicenter, blinded, placebo-controlled study to investigate the effects of everolimus and/or BEZ235 on the immune response to vaccination in the elderly.
Secondary ID [1] 283410 0
Nil
Universal Trial Number (UTN)
U1111-1149-3106
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Immune response to vaccination 290321 0
Condition category
Condition code
Inflammatory and Immune System 290719 290719 0 0
Normal development and function of the immune system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Everolimus, BEZ235 and corresponding placebo tablets and capsules will be dosed on a once-daily basis. Subjects will receive placebo, 0.1 mg or 0.5 mg everolimus daily, 10 mg BEZ235 daily, or a combination of 0.1 mg everolimus and 10 mg BEZ235 daily for 6 weeks.

Subjects will use a patient diary to record how many tablets are taken on each day. Subjects are required to bring back tablets or empty boxes to the clinic for drug accountability.

Standard flu vaccine (FluVax) will be given at day 56. Fluvax dose is 0.5ml and mode of delivery is intramuscular or deep subcutaneous injection.
Intervention code [1] 288134 0
Treatment: Drugs
Comparator / control treatment
*Everolimus 0.1 mg (1 tablet) daily or matched placebo (1 tablet)
*Everolimus 0.5 mg (2 x 0.25mg tablets) daily or matched placebo (2 tablets)
*BEZ235 10 mg (2 x 5mg tablet) daily or matched placebo (2 tablet)
*Everolimus 0.1 mg daily and BEZ235 10 mg (3 tablets) daily or matched placebo (3 tablets)
Control group
Placebo

Outcomes
Primary outcome [1] 290722 0
To assess the efficacy of low dose everolimus and/or BEZ235 in enhancing the immune response to vaccination in the elderly as determined by the change in hemagglutination inhibition (HI) geometric mean titers (GMTs) 4-weeks post influenza vaccination.

Assessed using serum assays.
Timepoint [1] 290722 0
4-weeks post influenza vaccination
Primary outcome [2] 290723 0
To assess the safety and tolerability of low dose everolimus and/or BEZ235 in the elderly. Assessed via adverse event reporting and safety labs (chemistry and haematology lab tests).

Known adverse events for both BEZ and everolimus include stomatitis, nausea, vomiting and diarrhoea.
Timepoint [2] 290723 0
Throughout trial participation (12 months)
Secondary outcome [1] 305094 0
To assess the efficacy of low dose everolimus and/or BEZ235 in enhancing the immune response to vaccination in the elderly as determined by rates of seroconversion and seroprotection 4-weeks post influenza vaccination

Assessed using serum assays.
Timepoint [1] 305094 0
4-weeks post influenza vaccination
Secondary outcome [2] 305095 0
To assess the efficacy of low dose everolimus and/or BEZ235 in enhancing the immune response to vaccination in the elderly as determined by the change in HI GMTs 1-week post influenza vaccination.

Assessed using serum assays.
Timepoint [2] 305095 0
1-week post influenza vaccination
Secondary outcome [3] 305096 0
To assess the PK of low dose everolimus and/or BEZ235 in the elderly.

Assessed using plasma assays and whole blood assays.
Timepoint [3] 305096 0
1h post blood withdrawal on day 28.

Eligibility
Key inclusion criteria
Informed Consent obtained
>= 65 yo, male and female
>=40kg
Minimum age
65 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Subjects with underlying unstable medical conditions.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Completed
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 outside Australia
Country [1] 5522 0
New Zealand
State/province [1] 5522 0

Funding & Sponsors
Funding source category [1] 288136 0
Commercial sector/Industry
Name [1] 288136 0
Novartis International AG
Address [1] 288136 0
Novartis International AG
CH-4002 Basel
Switzerland
Country [1] 288136 0
Switzerland
Primary sponsor type
Commercial sector/Industry
Name
Novartis Institutes for BioMedical Research
Address
220 Massachusetts Avenue Cambridge, MA 02139 USA
Country
United States of America
Secondary sponsor category [1] 286852 0
None
Name [1] 286852 0
Address [1] 286852 0
Country [1] 286852 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290048 0
Health and Disability Ethics Committees
Ethics committee address [1] 290048 0
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington 6145
Ethics committee country [1] 290048 0
New Zealand
Date submitted for ethics approval [1] 290048 0
17/10/2013
Approval date [1] 290048 0
04/12/2013
Ethics approval number [1] 290048 0

Summary
Brief summary
A proof of concept study to determine if inhibiting a protein with study drugs everolimus and/or BEZ235 enhances the immune response to vaccination in the elderly at doses that are safe and tolerable.
Trial website
Trial related presentations / publications
The trial has not yet been cited to date. There is, however, a full Clinical Study Report available and distributed to all participating sites.
Public notes

Contacts
Principal investigator
Name 43702 0
Dr Dean Quinn
Address 43702 0
P3 Research Limited
First Floor 121 Adelaide Road
Newtown
Wellington 6021, NEW ZEALAND
Country 43702 0
New Zealand
Phone 43702 0
+64 4 801 0002
Fax 43702 0
Email 43702 0
dean@p3research.co.nz
Contact person for public queries
Name 43703 0
Miss Jaybee David
Address 43703 0
Pharmaceutical Solutions Limited, Level 1, The Levy Building, 20 Customs Street East, Auckland CBD 1010
Country 43703 0
New Zealand
Phone 43703 0
+64 9 379 8205
Fax 43703 0
Email 43703 0
jaybeed@pharmasols.com
Contact person for scientific queries
Name 43704 0
Dr Joan Mannick
Address 43704 0
Novartis Institutes for BioMedical Research, Inc.
Clinical Science and Innovation
220 Massachusetts Avenue, 346J
Cambridge, MA 02139 USA
Country 43704 0
United States of America
Phone 43704 0
+1 617 871 5659
Fax 43704 0
Email 43704 0
joan.mannick@novartis.com