E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
juvenile-idiopathic arthritis paediatric uveitis |
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E.1.1.1 | Medical condition in easily understood language |
Inflammation of the joints and eyes |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022557 |
E.1.2 | Term | Intermediate uveitis |
E.1.2 | System Organ Class | 100000004853 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033687 |
E.1.2 | Term | Panuveitis |
E.1.2 | System Organ Class | 100000004853 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036370 |
E.1.2 | Term | Posterior uveitis |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066681 |
E.1.2 | Term | Acute uveitis |
E.1.2 | System Organ Class | 100000004853 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059176 |
E.1.2 | Term | Juvenile idiopathic arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
In patients with controlled JIA-associated uveitis, to compare rate of recurrence and time to recurrence of ocular inflammation in patients randomized to discontinue adalimumab compared to those who continue treatment. As a primary outcome, time to recurrence of ocular inflammation will be compared between the two treatment groups. Patients randomized to continue adalimumab will continue at their pre-randomization dose of no greater than 20 mg (if patient weighs < 30 kg) or 40 mg biweekly (if patient weighs ≥30 kg), administered subcutaneously. Patients stopping treatment will receive a volume-matched placebo injection biweekly. Secondary outcomes will include proportion of patients with ocular and arthritic flares, incidence of adverse events (AEs), best-corrected visual acuity (BCVA), treatment adherence, and quality of life among others.
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E.2.2 | Secondary objectives of the trial |
To determine predictors of recurrence in JIA-associated uveitis. Erythrocyte Sedimentation Rate (ESR), C-reactive Protein (CRP), anti-drug antibodies (ADA) to adalimumab, and serum MRP 8/14 (calprotectin) levels will be measured in patients in order to identify factors predictive of uveitis recurrence. Additional clinical characteristics, including age at diagnosis of arthritis, arthritis subtype, duration of uveitis inactivity prior to stopping, length of adalimumab treatment prior to stopping, and age at randomization will be assessed as potential predictors of uveitis recurrence.
To determine if stopping adalimumab leads to overall less control of inflammation at the 6 and 12-month visits, even if patients restart adalimumab after a uveitis recurrence. Patients randomized to stop treatment will have the option to restart treatment if they experience a treatment failure. Regardless of treatment course, we will assess clinical outcomes, such as recurrence of ocular inflammation, visu |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Stated willingness to comply with all study procedures and availability for the duration of the study period History of JIA diagnosed prior to 16 years of age 2 year of age or older Formal diagnosis of JIA-associated uveitis with no other suspected etiology ≥12 consecutive months of controlled ocular inflammation (≤0.5+ AC cell, ≤0.5+ vitreous haze, and no active retinal/choroidal lesions in either eye or macular edema) ≥ 12 consecutive months of controlled arthritis verified by a pediatric rheumatologist (see definition of controlled arthritis in Table 2) ≥12 consecutive months with adalimumab or a biosimilar ≥180 days on a stable dose of adalimumab or a biosimilar; must be a biweekly dose of no greater than 20 mg (if< 30kg) or 40 mg (if ≥30kg) If on a biosimilar of adalimumab, ≥90 days on biosimilar If on concomitant injectable or oral methotrexate or mycophenolate mofetil, dose must be ≤25 mg weekly for methotrexate or ≤3 g daily for mycophenolate mofetil 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 effective contraception or abstinence for ≥28 days prior to screening and throughout study period (for patients of reproductive age)
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E.4 | Principal exclusion criteria |
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 Acute or recurrent anterior uveitis characterized by redness and symptoms, including but not limited to: floaters, light sensitivity, pain Chronic hypotony (< 5 mmHg for ≥90 days) in either eye Treatment with oral corticosteroids or intraocular corticosteroid injections 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 (SGOT) or ALT (SGPT) ≥ 2 times the upper limit of normal range, creatinine ≥1.5 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is time to treatment failure (i.e., recurrence of ocular inflammation). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
proportion of patients with treatment failure (i.e., recurrence of ocular inflammation)
proportion of patients with corticosteroid-sparing control of ocular inflammation |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6 and 12 months
12 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 31 |