Adalimumab in JIA-associated Uveitis Stopping Trial (ADJUST)
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| ClinicalTrials.gov Identifier: NCT03816397 |
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Recruitment Status :
Recruiting
First Posted : January 25, 2019
Last Update Posted : May 13, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Uveitis JIA | Biological: Adalimumab Other: Placebo | Phase 4 |
Background: Juvenile idiopathic arthritis (JIA)-associated uveitis is a chronic paediatric ocular inflammatory condition that can result in visual impairment. Adalimumab, a tumour necrosis factor (TNF)-alpha inhibitor, effectively controls joint and eye inflammation; however, its long-term use may increase the risk of adverse health outcomes and place an undue financial burden on the patient and healthcare system given its high cost. There is great interest for patients to stop adalimumab following remission due to these reasons but there is a lack of information on the ability to maintain control after discontinuing adalimumab.
Methods: The Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Trial (ADJUST) is a multicentred, international trial that will randomise 118 participants aged 2 years and older with controlled JIA-associated uveitis to either continue adalimumab or discontinue adalimumab and receive a placebo. The trial will compare the time to uveitis recurrence between the two groups over 12 months. All participants will receive the standard weight-based dose of adalimumab or placebo: 20 mg biweekly (if < 30 kg) or 40 mg biweekly (if ≥ 30 kg).
Impact: This is the first randomised controlled trial to assess the efficacy of discontinuing adalimumab after demonstrating control of JIA-associated uveitis for at least 12 months. The results of ADJUST will provide information on clinical outcomes to guide clinicians in their decision-making regarding discontinuation of adalimumab.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 118 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial |
| Actual Study Start Date : | March 3, 2020 |
| Estimated Primary Completion Date : | January 31, 2024 |
| Estimated Study Completion Date : | January 31, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Continue adalimumab
Patients randomized to this arm will continue adalimumab at their current dose (either 20mg/0.2mL or 40mg/0.4mL) administered subcutaneously every other week.
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Biological: 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. The formulation is adalimumab, mannitol, polysorbate 80, and water for injection 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 Name: HUMIRA |
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Placebo Comparator: Stop adalimumab
Patients randomized to this arm will receive a volume-matched placebo (0.8mL) administered subcutaneously every other week.
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Other: Placebo
The placebo solution is a clear, colorless solution provided in a single-use, pre-filled syringe for subcutaneous injection. The placebo is designed to match the characteristics of the citrate-free adalimumab during injection. |
- Time to treatment failure [ Time Frame: From baseline until 12 months post-randomization ]
Time to treatment failure until 12 months post-randomization. Treatment failure is defined by recurrence of ocular inflammation in at least one eye as follows:
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3+ anterior chamber (AC) for a single visit
•>0.5+ anterior chamber (AC) cell for ≥28 days
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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. Treatment failure can also be declared by recurrence of joint inflammation that is persistent and severe enough to necessitate unmasking to manage the arthritis recurrence.
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| Ages Eligible for Study: | 2 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 diagnosed prior to 16 years of age (patient may be older than 16 at time of enrollment)
- ≥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 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)
- A negative tuberculosis (TB) test within the past 12 months or a positive test for TB with a history of completed treatment for latent TB
- Suitable, in the opinion of the Investigator, to continue treatment with adalimumab or placebo per regional labeling
- No contraindications to receive adalimumab as per the local Summary of Product Characteristics (SmPC)
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
- Current use of NSAID eye drops
- 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, active 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 sex, race, or ethnicity restrictions for this study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03816397
| Contact: Nisha Acharya, MD MS | 415-476-8131 | nisha.acharya@ucsf.edu |
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| Principal Investigator: | Nisha Acharya, MD MS | Principal Investigator |
| Responsible Party: | Nisha Acharya, Director, Uveitis and Ocular Inflammatory Disease Service, University of California, San Francisco |
| ClinicalTrials.gov Identifier: | NCT03816397 |
| Other Study ID Numbers: |
17-23987 UG1EY029658 ( U.S. NIH Grant/Contract ) |
| First Posted: | January 25, 2019 Key Record Dates |
| Last Update Posted: | May 13, 2021 |
| Last Verified: | May 2021 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Uveitis Uveal Diseases Eye Diseases |
Adalimumab Anti-Inflammatory Agents Antirheumatic Agents |