Juvenile Idiopathic Arthritis Associated Uveitis MedDRA version: 14.1 Level: PT Classification code 10046851 Term: Uveitis System Organ Class: 10015919 - Eye disorders
Conditions
Interventions
Product Name: Adalimumab (40mg)
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Adalimumab
CAS Number: 331731-18-1
Conc
Sponsors
University Hospitals Bristol NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A participant is eligible for the trial based upon at least one eye fulfilling the eligibility criteria. - Children and young people aged =2- =18 years fulfilling the ILAR diagnostic criteria for JIA (all subgroups that have uveitis) - At the time of trial screening the participant must have active anterior uveitis, defined as a "sustained grade of cellular infiltrate in anterior chamber of SUN criteria grade =1 + or more during the preceding 4 weeks therapy despite MTX and corticosteroid (both systemic and topical therapy) - Failed MTX (min dose of 10mg/ m2) for a minimum of 12 weeks - Disease modifying immunosuppressive drugs, other than MTX, discontinued at least 4 weeks before receiving the first dose of adalimumab. The dose of MTX must be stable for at least 12 weeks prior to the screening visit. - Written informed consent of participant or parent/ legal guardian, and assent where appropriate - Participant and parent/ legal guardian willing and able to comply with protocol requirements - For participants of reproductive potential (males and females), use of a reliable means of contraception throughout their trial participation. Post pubertal females must have a negative serum pregnancy test within 10 days before the first dose of trial drug. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Uveitis without a diagnosis of JIA Currently on adalimumab or has previously failed on adalimumab. Have been on other biologic agent within previous 5 half-lives of agent (For other biologic agents and their wash out periods, (refer to protocol supplementary document #10) More than 6 topical steroid eye drops per day at randomisation (this dose must have been stable for at least 4 weeks prior to screening visit) For patients on Prednisone or Prednisone equivalent, change of dose within 30 days prior to randomisation For patients on Prednisone or Prednisone equivalent with a dose >0.2mg/kg per day Intra-articular joint injections within four weeks prior to randomisation Any ongoing chronic or active infection (including infective uveitis) or any major episode of infection requiring hospitalisation or treatment with intravenous antibiotics within 30 days or oral antibiotics within 14 days prior to the screening evaluation History of active tuberculosis of less than 6 months treatment or untreated latent TB Participant has history of central nervous system (CNS) neoplasm, active CNS infection, demyelinating disease, or any progressive or degenerative neurological disease Poorly controlled diabetes or persistently poorly controlled severe hypertension (>95th percentile for height / age) as deemed by the treating physician Previous history of malignancy Intraocular surgery within the 3 months prior to screening (cataract/ glaucoma/ vitrectomy) Intra-ocular or peri-ocular corticosteroids within 30 days prior to randomisation. History of ocular herpetic disease Pregnant or nursing female Demonstrations of clinically significant deviations in any of the following laboratory parameters: Platelet count 2 x upper limit of normal (ULN) or serum bilirubin > 2x the ULN Glomerular filtration rate (GFR) of < 90 mL/min/1.73m2 [GFR (ml.min/1.73 m2 BSA) = 0.55 x height (cm)/plasma creatinine (mg/dl)] Hematocrit <24% Having been administered a live or attenuated vaccine within three months prior to screening Previous randomisation into the SYCAMORE trial to either arm of the trial. .
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare how effective the use of adalimumab, in combination with methotrexate versus methotrexate alone with regard to controlling disease activity in refractory uveitis associated with juvenile idiopathic arthritis.;Secondary Objective: - To evaluate the short term safety and tolerability of adalimumab in combination with methotrexate versus methotrexate alone with regards to complications of treatment, adverse events and laboratory assessments - To determine quality of life and cost effectiveness of adalimumab in combination with methotrexate versus methotrexate alone in patients with severe arthritis associated juvenile idiopathic arthritis - To determine clinical effectiveness of adalimumab in combination with methotrexate versus methotrexate alone with regards to underlying juvenile idiopathic arthritis disease activity - To determine the durability and magnitude of adalimumab efficacy response to sustaining inactive disease and achieve complete clinical remission - To determine the long term safety of adalimumab in combination with methotrexate versus methotrexate alone - To assess the efficacy of treatment with adalimumab to permit concomitant medication reduction, in particular steroids - To assess clinic;Primary end point(s): The primary endpoint is ‘time to treatment failure’. Treatment failure is defined by ONE or more of the following: 1)Anterior segment inflammatory score grade (SUN criteria) a)Following at least 3 months of therapy: i)2-Step increase in SUN cell activity score (AC Cells) over 2 consecutive readings ii)Sustained non-improvement with entry grade of 3 or greater for 2 consecutive readings iii)Only partial improvement (1 grade) with sustained development of other ocular co-morbidity* iv)Sustained scores as recorded at entry grade measured over 2 consecutive readings (grades 0.5 to 2) still present after 6 months of therapy. v)Worsening of existing (on enrolment) ocular co-morbidity after 3 m | — |
Countries
United Kingdom
Outcome results
None listed