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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03816397




Registration number
NCT03816397
Ethics application status
Date submitted
22/01/2019
Date registered
25/01/2019
Date last updated
25/01/2019

Titles & IDs
Public title
Adalimumab in JIA-associated Uveitis Stopping Trial
Scientific title
Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial
Secondary ID [1] 0 0
UG1EY029658
Secondary ID [2] 0 0
17-23987
Universal Trial Number (UTN)
Trial acronym
ADJUST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Uveitis 0 0
JIA 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
Other interventions - Placebo

Active Comparator: Continue adalimumab - Patients randomized to this arm will continue adalimumab at their current dose (either 20mg/0.8mL or 40mg/0.8mL) administered subcutaneously every other week.

Placebo Comparator: Stop adalimumab - Patients randomized to this arm will receive a volume-matched placebo (0.8mL) administered subcutaneously every other week.


Other interventions: Adalimumab
Adalimumab is a fully human monoclonal anti-tumor necrosis factor alpha antibody, a biologic, immunomodulatory drug. Adalimumab 20mg/0.8mL and 40mg/0.8mL is a clear, colorless solution provided in a pre-filled syringe for subcutaneous injection. Excipients include citric acid monohydrate, dibasic sodium phosphate dehydrate, mannitol, monobasic sodium phosphate dehydrate, polysorbate 80, sodium chloride, and water for injection. Sodium hydroxide is added as necessary to adjust pH. Each pre-filled syringe has a fixed 29-gauge thin wall and ½ inch needle with black protective cover and is intended for a single dose to a single patient.

Other interventions: Placebo
Volume-matched placebo

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to treatment failure - Time to treatment failure until 6 months post-randomization. Treatment failure is defined by recurrence of ocular inflammation as follows:
0.5+ anterior chamber (AC) cell for =60 days
•=2-step increase in AC cell observed at two separate visits =7 days apart
0.5+ vitreous haze, active retinal or choroidal inflammation, or macular edema observed at two separate visits =7 days apart
Timepoint [1] 0 0
From baseline until 6 months post-randomization
Secondary outcome [1] 0 0
Time to treatment failure - Time to treatment failure until 12 months post-randomization.
Timepoint [1] 0 0
From baseline until 12 months post-randomization

Eligibility
Key inclusion criteria
Inclusion Criteria (must meet all of the following to qualify):

- Stated willingness to comply with all study procedures and availability for the
duration of the study period

- = 2 years of age

- History of JIA-associated uveitis or uveitis of the same phenotype (chronic,
asymptomatic, anterior uveitis) diagnosed prior to 18 years of age with no other
suspected etiology of uveitis

- =12 consecutive months of controlled ocular inflammation (=0.5+ anterior chamber cell,
=0.5+ vitreous haze, no active retinal/choroidal lesions in either eye, no macular
edema)

- = 12 consecutive months of controlled arthritis verified by a pediatric rheumatologist

- =12 consecutive months and =5 years of treatment with adalimumab or a biosimilar of
adalimumab

- =180 days on a stable dose of adalimumab or a biosimilar; must be biweekly dose of
either 20mg (if<30kg) or 40mg (if =30kg)

- If on a biosimilar of adalimumab, =90 days on the biosimilar

- If on concomitant methotrexate, dose must be =25mg weekly and stable for =90 days

- If on concomitant mycophenolate mofetil, dose must be =3g daily and stable for =90
days

- If on topical corticosteroids, dose must be =2 drops prednisolone acetate 1% or
equivalent per day and stable for =90 days

- Willingness to limit consumption of alcohol during the study period

- Agreement to avoid live attenuated vaccinations

- Agreement to use highly effective contraception for =28 days prior to screening and
throughout study period (for males and females of reproductive age)
Minimum age
2 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria (any one of these excludes the patient):

- Intraocular surgery in the past 90 days or planned surgery in the next 180 days

- Severe cataract or opacity preventing view to the posterior pole in both eyes

- Chronic hypotony (<5mmHg for =90 days) in either eye

- Treatment with oral corticosteroids or intraocular corticosteroid injection within the
last 12 months

- Acute anterior uveitis characterized by redness and symptoms, including but not
limited to floaters, pain, and light sensitivity

- Pregnancy or lactation (a pregnancy test will be conducted at baseline and all
follow-up visits for females of reproductive age)

- Prior safety or tolerability issues with adalimumab

- History of cancer, tuberculosis, or hepatitis B

- Other medical condition expected to dictate treatment course during the study

- Any of the following abnormal lab values within 28 days prior to enrollment: leukocyte
count <2500, platelet count =75000, hemoglobin<9.0, AST or ALT = 2 times the upper
limit of normal range, creatinine =1.5

There are no gender, race, or ethnicity restrictions for this study.

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?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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)
Recruitment hospital [1] 0 0
The Royal Children's Hospital Melbourne - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville
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
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Utah
Country [7] 0 0
United States of America
State/province [7] 0 0
Washington
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Bristol
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Liverpool
Country [10] 0 0
United Kingdom
State/province [10] 0 0
London
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Newcastle Upon Tyne
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Sheffield
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Other
Name
Nisha Acharya
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Children's Hospital of Philadelphia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Children's Hospital Medical Center, Cincinnati
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Children's Mercy Hospital Kansas City
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Government body
Name [4] 0 0
National Eye Institute (NEI)
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Great Ormond Street Hospital for Children NHS Foundation Trust
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
University Hospitals Bristol NHS Foundation Trust
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
Alder Hey Children's NHS Foundation Trust
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
Johns Hopkins University
Address [8] 0 0
Country [8] 0 0
Other collaborator category [9] 0 0
Other
Name [9] 0 0
Children's Hospital Los Angeles
Address [9] 0 0
Country [9] 0 0
Other collaborator category [10] 0 0
Other
Name [10] 0 0
Seattle Children's Hospital
Address [10] 0 0
Country [10] 0 0
Other collaborator category [11] 0 0
Other
Name [11] 0 0
Newcastle-upon-Tyne Hospitals NHS Trust
Address [11] 0 0
Country [11] 0 0
Other collaborator category [12] 0 0
Other
Name [12] 0 0
University Hospital Southampton NHS Foundation Trust
Address [12] 0 0
Country [12] 0 0
Other collaborator category [13] 0 0
Other
Name [13] 0 0
Sheffield Children's NHS Foundation Trust
Address [13] 0 0
Country [13] 0 0
Other collaborator category [14] 0 0
Other
Name [14] 0 0
The Royal Children's Hospital
Address [14] 0 0
Country [14] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The proposed study is a stratified, block-randomized, double-masked, controlled trial to
determine the feasibility of discontinuing adalimumab treatment in patients with quiescent
uveitis associated with juvenile idiopathic arthritis (JIA).
Trial website
https://clinicaltrials.gov/show/NCT03816397
Trial related presentations / publications
Jaffe GJ, Dick AD, Brézin AP, Nguyen QD, Thorne JE, Kestelyn P, Barisani-Asenbauer T, Franco P, Heiligenhaus A, Scales D, Chu DS, Camez A, Kwatra NV, Song AP, Kron M, Tari S, Suhler EB. Adalimumab in Patients with Active Noninfectious Uveitis. N Engl J Med. 2016 Sep 8;375(10):932-43. doi: 10.1056/NEJMoa1509852.
Nguyen QD, Merrill PT, Jaffe GJ, Dick AD, Kurup SK, Sheppard J, Schlaen A, Pavesio C, Cimino L, Van Calster J, Camez AA, Kwatra NV, Song AP, Kron M, Tari S, Brézin AP. Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet. 2016 Sep 17;388(10050):1183-92. doi: 10.1016/S0140-6736(16)31339-3. Epub 2016 Aug 16. Erratum in: Lancet. 2016 Sep 17;388(10050):1160.
Ramanan AV, Dick AD, Benton D, Compeyrot-Lacassagne S, Dawoud D, Hardwick B, Hickey H, Hughes D, Jones A, Woo P, Edelsten C, Beresford MW; SYCAMORE Trial Management Group. A randomised controlled trial of the clinical effectiveness, safety and cost-effectiveness of adalimumab in combination with methotrexate for the treatment of juvenile idiopathic arthritis associated uveitis (SYCAMORE Trial). Trials. 2014 Jan 9;15:14. doi: 10.1186/1745-6215-15-14.
Vazquez-Cobian LB, Flynn T, Lehman TJ. Adalimumab therapy for childhood uveitis. J Pediatr. 2006 Oct;149(4):572-5.
Chang CY, Meyer RM, Reiff AO. Impact of medication withdrawal method on flare-free survival in patients with juvenile idiopathic arthritis on combination therapy. Arthritis Care Res (Hoboken). 2015 May;67(5):658-66. doi: 10.1002/acr.22477.
Baszis K, Garbutt J, Toib D, Mao J, King A, White A, French A. Clinical outcomes after withdrawal of anti-tumor necrosis factor a therapy in patients with juvenile idiopathic arthritis: a twelve-year experience. Arthritis Rheum. 2011 Oct;63(10):3163-8. doi: 10.1002/art.30502.
Shakoor A, Esterberg E, Acharya NR. Recurrence of uveitis after discontinuation of infliximab. Ocul Immunol Inflamm. 2014 Apr;22(2):96-101. doi: 10.3109/09273948.2013.812222. Epub 2013 Jul 22.
Public notes

Contacts
Principal investigator
Name 0 0
Nisha Acharya, MD MS
Address 0 0
Principal Investigator
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Nisha Acharya, MD MS
Address 0 0
Country 0 0
Phone 0 0
415-476-8131
Fax 0 0
Email 0 0
nisha.acharya@ucsf.edu
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03816397