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Trial registered on ANZCTR


Registration number
ACTRN12618000365268
Ethics application status
Approved
Date submitted
22/02/2018
Date registered
9/03/2018
Date last updated
17/02/2020
Date data sharing statement initially provided
2/11/2018
Date results provided
2/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A clinical research study to find out if the oral medication everolimus alone or combination with BEZ235 is safe and enhances the immune response to influenza vaccination in people 65 years of age or older when dosing begins 2 weeks before or at the same time as an influenza vaccination.
Scientific title
A multicenter, double-blind, placebo-controlled study to investigate the effects of oral everolimus alone or in combination with BEZ235 on the immune response to influenza vaccination in the elderly at increased risk of influenza illness.
Secondary ID [1] 294103 0
RTB-101- 203
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory Tract Infections 306694 0
Influenza 306796 0
Condition category
Condition code
Respiratory 305793 305793 0 0
Other respiratory disorders / diseases
Infection 305902 305902 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Everolimus (oral tablets) alone or together with BEZ235 (oral capsules) and corresponding placebo oral tablets and oral capsules will be dosed on a once daily basis. Subjects will be randomized to receive placebo, or 0.1 mg everolimus alone or in a combination of 0.1 mg everolimus and 10 mg BEZ235 once daily for either 4 weeks (Group A) or 6 weeks (Group B).

Group A (receive influenza vaccination at baseline and start dosing after vaccination at baseline visit for a period of 4 weeks. Total treatment period is 4 weeks)
I. Everolimus 0.1 mg or matched placebo
II. Everolimus 0.1 mg plus 10 mg BEZ235 (combination) or matched placebo

Group B (receive study drug for 2 weeks starting at the baseline visit and then receive influenza vaccination at week 2 and then continue dosing for an additional 4 weeks. Total treatment period is 6 weeks).
III. Everolimus 0.1 mg or matched placebo
IV. Everolimus 0.1 mg plus 10 mg BEZ235 (combination) or matched placebo

Subjects will then be followed for 1 week off study drug.

Compliance will be assessed by the investigator and/or study personnel at each visit by having subjects bring remaining study drug to each visit and having the site staff count the remaining number of capsules and/or tablets and having this information recorded in the eCRF.
Intervention code [1] 300380 0
Prevention
Comparator / control treatment
Placebo will be used as the control in each group/arm.
BEZ235 matching placebo is a hard gelatin capsule with the same content minus the active ingredient. The everolimus placebo is a tablet with similar ingredients as the everolimus tablets, minus the active ingredient.
Control group
Placebo

Outcomes
Primary outcome [1] 304861 0
To determine if everolimus alone or combination with BEZ235 enhances the immune response to vaccination in the elderly as determined by the change in hemagglutination inhibition (HI) geometric mean titers 4-weeks post influenza vaccination
Timepoint [1] 304861 0
4 weeks post influenza vaccination.
Secondary outcome [1] 343398 0
To assess the efficacy of everolimus alone or in combination with BEZ235 in enhancing the immune response to vaccination in the elderly as determined by rate of seroconversion 4-weeks post influenza vaccination.
Seroconversion to be assessed by blood tests.
Timepoint [1] 343398 0
4 weeks post influenza vaccination.
Secondary outcome [2] 343399 0
To assess the safety and tolerability of everolimus alone or in combination with BEZ235 when given 2 weeks before or at the same time as influenza vaccination.
This outcome will be assessed by following adverse event reports, safety labs (haematology and chemistry) and physical exams. Examples of possible adverse events; Mouth ulcers, Gastrointestinal symptoms, Fatigue, Headache, Rash, Increased glucose levels, Decreased blood cell counts, Increased cholesterol levels, Liver or Kidney Damage, Lung Inflammation, Angioedema, Peripheral oedema, Change in taste, Bloody nose, Irritation of mucous membranes, Decreased weight, Itching, Cough, Dry skin, Nail disorder, Fever.
Timepoint [2] 343399 0
Timepoints: Physical examination at baseline, targeted physical examination (oral, skin, lungs) at Day 2, Week 2, Week 4, Week 5 (Group A), Week 6 (Group B only), Week 7 (Group B). Safety labs at each visit and adverse event reporting as required during study.
Secondary outcome [3] 343466 0
To determine if everolimus alone or in combination with BEZ235 increases antiviral gene expression 4 hours after dosing
Timepoint [3] 343466 0
4 hours after dosing.
Secondary outcome [4] 343767 0
To assess the efficacy of everolimus alone or in combination with BEZ235 in enhancing the immune response to vaccination in the elderly as determined by rate of seroprotection 4-weeks post influenza vaccination.
Seroprotection to be assessed by blood tests.
Timepoint [4] 343767 0
4 weeks post influenza vaccination.

Eligibility
Key inclusion criteria
1. Male and female subjects
a. Age greater than or equal to 85 years
b. Age greater than or equal to 65 years and < 85 years with one or more of the following conditions
i. Asthma
ii. COPD Gold Class I or II
iii. T2DM
iv. CHF New York Heart Association functional classification I-II
v. Current smoker
vi. One or more emergency room visits or hospitalizations for a RTI during the previous 12 months
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. The following cardiac conditions:
a. Unstable angina pectoris or acute ischemic changes on ECG at screening.
b. History of myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI) within 6 months prior to screening.
c. Ventricular arrhythmias except for benign premature ventricular contractions
d. Supraventricular and nodal arrhythmias not controlled with medication or a pacemaker.
e. Symptomatic pericarditis.
f. New York Heart Association functional classification III-IV CHF.
g. History of familial long QT syndrome or known family history of Torsades de Pointes.
2. History of malignancy in any organ system.
3. Subjects with active infection.
4. Subjects with Type I diabetes mellitus.
5. Subjects with clinically significant underlying pulmonary disease.
6. Subjects with a history of a systemic autoimmune disease or receiving immunosuppressive therapy including prednisone > 10 mg for chronic use,
7. Recent major surgery (such as involving entry into a body cavity) within 2 months of the screening visit or any evidence of unhealed surgical wound or lack of significant recovery from the surgery.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by phone/fax/email.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation and sequence generation will be done via a computer system.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
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
18/04/2018
Actual
11/05/2018
Date of last participant enrolment
Anticipated
25/05/2018
Actual
11/07/2018
Date of last data collection
Anticipated
13/07/2018
Actual
20/08/2018
Sample size
Target
300
Accrual to date
Final
253
Recruitment outside Australia
Country [1] 9608 0
New Zealand
State/province [1] 9608 0

Funding & Sponsors
Funding source category [1] 298735 0
Commercial sector/Industry
Name [1] 298735 0
resTORbio Inc.
Country [1] 298735 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
resTORbio Inc.
Address
500 Boylston Street
12th floor
Boston MA 02116
United States of America
Country
United States of America
Secondary sponsor category [1] 297911 0
None
Name [1] 297911 0
Address [1] 297911 0
Country [1] 297911 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299678 0
Health and Disability Ethics Committee
Ethics committee address [1] 299678 0
Ethics committee country [1] 299678 0
New Zealand
Date submitted for ethics approval [1] 299678 0
22/02/2018
Approval date [1] 299678 0
06/04/2018
Ethics approval number [1] 299678 0
18/NTB/40

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81266 0
Dr Simon Carson
Address 81266 0
Southern Clinical Trials Group Ltd
3 Strickland St
Beckenham
Christchurch 8024
New Zealand
Country 81266 0
New Zealand
Phone 81266 0
+64 3 337 1979
Fax 81266 0
Email 81266 0
simon@sctrials.co.nz
Contact person for public queries
Name 81267 0
Elaine Gent
Address 81267 0
Pharmaceutical Solutions
Level 1, The Levy Building,
20 Customs Street East,
Auckland 1010
Country 81267 0
New Zealand
Phone 81267 0
+6493798205
Fax 81267 0
Email 81267 0
elaineg@pharmasols.com
Contact person for scientific queries
Name 81268 0
Elaine Gent
Address 81268 0
Pharmaceutical Solutions
Level 1, The Levy Building,
20 Customs Street East,
Auckland 1010
Country 81268 0
New Zealand
Phone 81268 0
+6493798205
Fax 81268 0
Email 81268 0
elaineg@pharmasols.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Raw data from participants will not be shared due to privacy


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.