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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03828019




Registration number
NCT03828019
Ethics application status
Date submitted
28/01/2019
Date registered
4/02/2019

Titles & IDs
Public title
Adalimumab vs. Conventional Immunosuppression for Uveitis Trial
Scientific title
Adalimumab vs. Conventional Immunosuppression for Uveitis Trial
Secondary ID [1] 0 0
9196
Universal Trial Number (UTN)
Trial acronym
ADVISE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Uveitis 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Adalimumab (ADA)
Treatment: Drugs - Conventional immunosuppression (CON)

Active comparator: Adalimumab (ADA) - Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months.

Adults (= 18 years of age) and adolescents =30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks.

Active comparator: Conventional immunosuppression (CON) - Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration.

Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID.


Treatment: Other: Adalimumab (ADA)
Adalimumab is a fully-human monoclonal antibody to TNF-a, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.

Treatment: Drugs: Conventional immunosuppression (CON)
The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Corticosteroid-sparing treatment success within the first 6 months after randomization
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
Corticosteroid-sparing treatment success within the first 12 months after randomization
Timepoint [1] 0 0
12 months
Secondary outcome [2] 0 0
Prednisone discontinuation success
Timepoint [2] 0 0
12 months
Secondary outcome [3] 0 0
Prednisone exposure
Timepoint [3] 0 0
12 months
Secondary outcome [4] 0 0
Best corrected visual acuity
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Infections
Timepoint [5] 0 0
12 months
Secondary outcome [6] 0 0
Systemic adverse events
Timepoint [6] 0 0
12 months
Secondary outcome [7] 0 0
Macular edema
Timepoint [7] 0 0
12 months
Secondary outcome [8] 0 0
Health utility
Timepoint [8] 0 0
12 months
Secondary outcome [9] 0 0
Generic health-related quality of life
Timepoint [9] 0 0
12 months
Secondary outcome [10] 0 0
Vision-related quality of life
Timepoint [10] 0 0
12 months

Eligibility
Key inclusion criteria
Inclusion criteria

1. Age 13 years or older
2. Weight 30 kg (66 lbs) or greater
3. Active or recently active (= 60 days) non-infectious intermediate, posterior, or panuveitis
4. Prednisone indication meets one of the following:

1. Active uveitis requiring one of the following i. Initiation of prednisone at dose greater than 7.5 mg/day ii. Increasing prednisone dose to greater than 7.5 mg/day iii. Currently receiving dose greater than 7.5 mg/day
2. Inactive uveitis on current dose greater 7.5 mg/day
5. Initiation or addition of an immunosuppressive drug (i.e., a conventional immunosuppressive drug or adalimumab) is indicated
6. If currently receiving a conventional immunosuppressive drug, the drug and dose have been stable for at least 30 days
7. Patient able and willing to self-administer subcutaneous injections or have a qualified person available to administer subcutaneous injections
8. If posterior segment disease is present, ability to assess activity in at least one eye with uveitis
9. Visual acuity of light perception or better in at least one eye with uveitis
Minimum age
13 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria

1. Active tuberculosis or untreated latent tuberculosis (e.g., positive interferon-? release assay [IGRA] test, such as Quantiferon-gold)
2. Untreated active hepatitis B or C infection
3. Any of the following baseline lab values

1. White blood count <3500 cells per microliter
2. Platelets <100,000 per microliter
3. Hematocrit <30%
4. AST or ALT >1.5X upper limit normal value
5. Serum creatinine >1.1X upper limit normal value
4. Behçet disease
5. Multiple sclerosis or other demyelinating disease
6. For patients with anterior/intermediate or intermediate uveitis without systemic disease, abnormal magnetic resonance imaging (MRI) of the brain consistent with demyelinating disease
7. Severe uncontrolled infection
8. Receipt of a live vaccine within past 30 days
9. Moderate to severe heart failure (NYHA class III/IV)
10. Active malignancy
11. Use of anti-TNF monoclonal antibody therapy within past 60 days
12. History of adalimumab intolerance or ineffectiveness
13. Hypersensitivity to any of the study treatments or their excipients
14. Current treatment with an alkylating agent
15. Current treatment with more than one immunosuppressive drug, not including oral corticosteroids
16. Shorter-acting regional corticosteroids administered within the past 30 days in any eye(s) with uveitis
17. Long-acting ocular corticosteroid implants, i.e., fluocinolone acetonide implant (e.g., Retisert®, YutiqTM, Iluvien®) placed within past 3 years unless uveitis is active in all eye(s) with an implant
18. Systemic disease that is sufficiently active such that it dictates therapy with systemic corticosteroids or immunosuppressive agents at the time of enrollment
19. Immunodeficiency disease for which immunosuppressive therapy would be contraindicated according to best medical judgment
20. Pregnancy or lactation
21. For persons of child-bearing potential or impregnating potential, unwillingness to use appropriate birth control (abstinence, combination barrier and spermicide, hormonal, or intrauterine device) for the next 18 months or plans to become a biological parent within the next 18 months.

* In the UK, use of combination barrier and spermicide alone does not meet birth control requirements.

† UK female study participants must use highly effective methods of contraception.

UK male study participants must use condoms for at least 6 months after the end of study treatment and their female partners of child-bearing potential are recommended to use highly effective contraception for the same duration. In addition, male participants should not donate semen during therapy or for 6 months following discontinuation of study treatment.
22. Medical problems or drug or alcohol dependence problems sufficient to prevent adherence to treatment and study procedures.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/09/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
17/09/2024
Actual
Sample size
Target
222
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Centre for Eye Research Australia - East Melbourne
Recruitment hospital [2] 0 0
University of Sydney - Sydney
Recruitment postcode(s) [1] 0 0
- East Melbourne
Recruitment postcode(s) [2] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Canada
State/province [15] 0 0
Quebec
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Birmingham
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Bradford
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Cambridge
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Leicester
Country [20] 0 0
United Kingdom
State/province [20] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
JHSPH Center for Clinical Trials
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Douglas A Jabs, MD MBA
Address 0 0
CCTand Evidence Synthesis, JHU, Bloomberg School of Public Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
A public use dataset corresponding to the primary manuscript and compliant with HIPAA regulations will be prepared within 1 year of completion of data collection. An encrypted data set containing de-identified data, a data dictionary and other study documentation (e.g. protocol and study manuals) will be provide after the data use agreement has been executed (see access criteria below).

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
One year after completion of data collection, the data set will be available upon request .
Available to whom?
Requests for access to data will be reviewed by the Executive Committee to confirm oversight authority approval (e.g. IRB approval) and a minimum standard of scientific merit. Once a request is approved, the investigator will be required to sign a data use agreement approved by the Johns Hopkins Bloomberg School of Public Health Office of Research Administration. An encrypted data set containing de-identified data, a data dictionary and other study documentation (e.g. protocol and study manuals) will be provide after the data use agreement has been executed.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03828019