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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03828019
Ethics application status
Date submitted
28/01/2019
Date registered
4/02/2019
Date last updated
7/06/2019

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
Other interventions - 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.


Other interventions: 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
Other interventions
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 - Corticosteroid-sparing success is defined as achieving inactive uveitis for two consecutive visits >= 28 days apart while on <= 7.5 mg/day of corticosteroids. Uveitis status (active vs inactive) is determined by the study ophthalmologist after reviewing the eye exam and imaging.
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
Corticosteroid-sparing treatment success within the first 12 months after randomization - Corticosteroid-sparing success is defined as achieving inactive uveitis for two consecutive visits >= 28 days apart while on <= 7.5 mg/day of corticosteroids. Uveitis status (active vs inactive) is determined by the study ophthalmologist after reviewing the eye exam and imaging.
Timepoint [1] 0 0
12 months
Secondary outcome [2] 0 0
Prednisone discontinuation success - Prednisone discontinuation success is defined as achieving inactive uveitis for two consecutive visits >= 28 days apart after discontinuing corticosteroids. Uveitis status (active vs inactive) is determined by the study ophthalmologist after reviewing the eye exam and imaging.
Timepoint [2] 0 0
12 months
Secondary outcome [3] 0 0
Prednisone exposure - E.g., cumulative prednisone dose and/or mean prednisone dose
Timepoint [3] 0 0
12 months
Secondary outcome [4] 0 0
Best corrected visual acuity - Best corrected visual acuity measured after a standardized refraction using logarithmic visual acuity charts
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Infections - Incidence of infections over 12 months of follow-up
Timepoint [5] 0 0
12 months
Secondary outcome [6] 0 0
Systemic adverse events - Systemic adverse events over 12 months of follow-up
Timepoint [6] 0 0
12 months
Secondary outcome [7] 0 0
Macular edema - Macular edema over 12 months of follow-up
Timepoint [7] 0 0
12 months
Secondary outcome [8] 0 0
Health utility - Health utility will be measured using the EQ-5D
Timepoint [8] 0 0
12 months
Secondary outcome [9] 0 0
Generic health-related quality of life - Generic health-related quality of life will be measured using the SF-36
Timepoint [9] 0 0
12 months
Secondary outcome [10] 0 0
Vision-related quality of life - Vision-related quality of life will be measured using the NEI-VFQ-25
Timepoint [10] 0 0
12 months

Eligibility
Key inclusion criteria
1. Age 13 years or older

2. Active or recently active (= 60 days) non-infectious, intermediate, posterior, or
panuveitis

3. Prednisone indication meets one of the following:

a. 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

b. Inactive uveitis on current dose greater 7.5 mg/day

4. Initiation or addition of an immunosuppressive drug (i.e., a conventional
immunosuppressive drug or adalimumab) is indicated

5. If currently receiving a conventional immunosuppressive drug, the drug and dose have
been stable for at least 30 days

6. Patient able and willing to self-administer subcutaneous injections or have a
qualified person available to administer subcutaneous injections

7. If posterior segment disease is present, ability to assess activity in at least one
eye with uveitis

8. Visual acuity of light perception or better in at least one eye with uveitis
Minimum age
13 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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. Behçet disease

4. Multiple sclerosis

5. For patients with intermediate uveitis, abnormal magnetic resonance imaging (MRI) of
the brain consistent with demyelinating disease

6. Use of anti-TNF monoclonal antibody therapy within past 60 days

7. History of adalimumab intolerance or ineffectiveness

8. Current treatment with an alkylating agent

9. Current treatment with more than one immunosuppressive drug, not including oral
corticosteroids

10. Shorter-acting regional corticosteroids administered within the past 30 days in any
eye(s) with uveitis

11. 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

12. Systemic disease that is sufficiently active such that it dictates therapy with
systemic corticosteroids or immunosuppressive agents at the time of enrollment

13. Immunodeficiency disease for which immunosuppressive therapy would be contraindicated
according to best medical judgment

14. Pregnancy, lactation, or for women of child-bearing potential unwillingness to use
appropriate birth control for the duration of the trial

15. 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
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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] 0 0
Centre for Eye Research Australia - East Melbourne
Recruitment postcode(s) [1] 0 0
- East Melbourne
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
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Birmingham
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Oxford
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Bristol
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Cambridge
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Leicester
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Liverpool
Country [24] 0 0
United Kingdom
State/province [24] 0 0
London
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Manchester

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

Ethics approval
Ethics application status

Summary
Brief summary
Non-infectious intermediate, posterior, and panuveitides are chronic, potentially-blinding
diseases. Vision-threatening cases require long-term therapy with oral corticosteroids and
immunosuppression. Based upon preliminary data, adalimumab, a fully-human, anti-TNF-a
monoclonal antibody, now US FDA-approved for uveitis treatment, may be a superior
corticosteroid-sparing agent than conventional immunosuppressive drugs. The ADVISE Trial is
multicenter randomized, parallel-treatment, comparative effectiveness trial comparing
adalimumab to conventional (small molecule) immunosuppression for corticosteroid spring in
the treatment of non-infectious, intermediate, posterior, and panuveitides.
Trial website
https://clinicaltrials.gov/show/NCT03828019
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Douglas A Jabs, MD MBA
Address 0 0
Icahn School of Medicine, Mount Sinai, New York, NY
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Janet T Holbrook, PhD MPH
Address 0 0
Country 0 0
Phone 0 0
443-287-5791
Fax 0 0
Email 0 0
jholbro1@jhu.edu
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03828019