Uveitis Clinical Trial
— ADJUVITEOfficial title:
Evaluation of the Efficacy of Adalimumab for the Treatment of Uveitis in Juvenile Idiopathic Arthritis: Randomized Double-blind Placebo-controlled Trial
Verified date | December 2017 |
Source | Assistance Publique - Hôpitaux de Paris |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The investigators propose to study the efficacy of adalimumab versus placebo (double-blind randomization on inclusion into 2 equal groups) on reduction of ocular inflammation quantified by laser flare photometry after two months of treatment in patients with active uveitis despite well conducted treatment with steroid eye drops and MTX. The primary objective is to demonstrate a higher response rate at 2 months in the adalimumab arm versus the placebo arm. Will be considered as responding patients those in whom the evaluated eye, 2 months after inclusion, presents at least 30% reduction of inflammation on laser flare photometry and improvement or a stable appearance on slit lamp examination. After the second month, all patients wishing to continue the trial and presenting a satisfactory clinical state will be treated with adalimumab for a total of one year after inclusion to descriptively evaluate the efficacy and safety of treatment over 10 to 12 months.
Status | Completed |
Enrollment | 34 |
Est. completion date | August 27, 2015 |
Est. primary completion date | November 4, 2014 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 4 Years and older |
Eligibility |
Inclusion Criteria: 1. Active uveitis associated with juvenile idiopathic arthritis, with the exclusion of systemic JIA, juvenile-onset rheumatoid arthritis, and enthesitis-related JIA 2. Uveitis resistant to well conducted topical steroid therapy comprising either dexamethasone or rimexolone at a dose adapted to the patient's situation as validated by one of the investigating ophthalmologists. 3. Failure of systemic treatment with methotrexate at a dose of 0.3 to 0.6 mg.kg (without exceeding 25 mg) once a week for at least 3 months (except in the case of methotrexate intolerance). 4. Patient who can be evaluated by laser flare photometry. 5. Patient at least 4 years old on initiation of trial medication and weighing a minimum of 15 kg 6. Signed informed consent both parents and/or patient's agreement 7. Patient has a social security or similar Exclusion Criteria: 1. Systemic JIA, juvenile-onset rheumatoid arthritis, enthesitis-related JIA (with a risk of red eye uveitis). 2. History of treatment with anti-TNF alpha monoclonal antibody (either adalimumab or infliximab). 3. Any contraindication to administration of immunosuppressive therapy (immune deficit, opportunistic infection, other severe chronic disease) - History of cancer or lymphoproliferative disease other than successfully and completely resected squamous cell or basal cell skin cancer, - Any uncontrolled disease: unstable diabetes with documented history of recurrent infections, unstable ischaemic heart disease, moderate to severe heart failure (NYHA stage III/IV), recent stroke and any other disease or condition inducing, in the investigator's opinion, a risk for the patient related to his/her participation in the trial, - Positive hepatitis B or C serology indicating active infection, - History of positive HIV serology, - Persistent infection or severe infections requiring hospitalisation or IV antibiotic therapy during the 30 days prior to inclusion in the trial or oral antibiotic therapy during the 14 days prior to inclusion in the trial, - History of clinically significant alcohol or other substance abuse during the previous year, - Previous diagnosis or signs of demyelinating disease of the central nervous system, - History of active tuberculosis, histoplasmosis or listeriosis, - Signs of latent tuberculosis (based on a history of nontreated contamination, or an opacity greater than 1 cm on chest x-ray, or a positive intradermal reaction to 5 IU of tuberculin = 5 mm). - Negative urine pregnancy test in girls with childbearing potential 4. Chronic rupture of the blood-aqueous barrier with marked flare on the initial examination but not modified by one month of anti-inflammatory therapy. 5. Impossibility to monitor flare: - Children < 4 years - False flare due to the presence of giant cells on the surface of an artificial lens or in an aphakic child. 6. Children presenting complications such as refractory glaucoma or cataract rapidly requiring surgery. 7. Phthisis bulbi with hypotonia and atrophy of the ciliary body. 8. Any other situation raising problems for maintenance of stable doses of steroids and immunosuppressive drugs during the period between 4 weeks before D0 and the M2 evaluation. Authorized immunosuppressive therapies that must be maintained at stable dose are steroid eye drops, systemic steroid therapy and once weekly oral or subcutaneous MTX at a dose of 0.3 to 0.6 mg (without exceeding 25 mg). 9. Any ophthalmologic contraindication 10. If female and childbearing potential should have an appropriate contraceptive method during all study period and 5 months after last adalimumab dose. Abstinence with no oral contraception can be considered. |
Country | Name | City | State |
---|---|---|---|
France | Hospital of necker Enfants malades | Paris |
Lead Sponsor | Collaborator |
---|---|
Assistance Publique - Hôpitaux de Paris | Abbott |
France,
Biester S, Deuter C, Michels H, Haefner R, Kuemmerle-Deschner J, Doycheva D, Zierhut M. Adalimumab in the therapy of uveitis in childhood. Br J Ophthalmol. 2007 Mar;91(3):319-24. Epub 2006 Oct 11. — View Citation
Callejas-Rubio JL, Sánchez-Cano D, Serrano JL, Ortego-Centeno N. Adalimumab therapy for refractory uveitis: a pilot study. J Ocul Pharmacol Ther. 2008 Dec;24(6):613-4; author reply 614. doi: 10.1089/jop.2008.0073. — View Citation
Simonini G, Taddio A, Cattalini M, Caputo R, De Libero C, Naviglio S, Bresci C, Lorusso M, Lepore L, Cimaz R. Prevention of flare recurrences in childhood-refractory chronic uveitis: an open-label comparative study of adalimumab versus infliximab. Arthritis Care Res (Hoboken). 2011 Apr;63(4):612-8. doi: 10.1002/acr.20404. — View Citation
Tynjälä P, Kotaniemi K, Lindahl P, Latva K, Aalto K, Honkanen V, Lahdenne P. Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis. Rheumatology (Oxford). 2008 Mar;47(3):339-44. doi: 10.1093/rheumatology/kem356. Epub 2008 Jan 31. — View Citation
Vazquez-Cobian LB, Flynn T, Lehman TJ. Adalimumab therapy for childhood uveitis. J Pediatr. 2006 Oct;149(4):572-5. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | To demonstrate that a higher proportion of subjects will have an improvement of uveitis on adalimumab versus placebo after 2 months relative to baseline | The primary objective is to demonstrate the efficacy of 2 months of treatment with adalimumab versus placebo on reduction of ocular inflammation in JIA-associated uveitis. By defining response to treatment as a reduction of at least 30% of ocular inflammation quantified by laser flare photometry in the initially more severely inflamed eye without deterioration of cell count or flare protein on slit lamp examination, we formulate the hypothesis that at least 50% of patients treated with adalimumab for 2 months will respond to treatment versus a maximum 10% of patients on placebo. |
Final visit could occur at any point up to 78 weeks | |
Secondary | Evaluation of adverse events | To evaluate the safety of treatment at 2 months then at 12 months | 12 months | |
Secondary | Proportion of subjects at each study time point with an improvement of uveitis | To evaluate the response of the treatment on ocular inflammation quantified by slit lamp examination and laser flare photometry at each visit comparatively between the adalimumab arm and the placebo arm during the double-blind period (until M2, as a complement to the laser flare photometry evaluation performed for the primary objective) and then descriptively on adalimumab. Analyses will be performed on the eye evaluated for the primary objective and for the fellow eye in patients with bilateral uveitis. | 2 months | |
Secondary | Eyes with active uveitis | To compare the proportion of eyes with active uveitis on inclusion improved after 2 months between the adalimumab arm and the placebo arm | 2 months | |
Secondary | The efficacy of treatment on juvenile idiopathic arthritis | To evaluate the efficacy of treatment on JIA, particularly the joint lesions at each visit, comparatively between the adalimumab arm and the placebo arm until M2 then descriptively on adalimumab | 2 months | |
Secondary | Decrease topical or systemic steroid therapy | To evaluate the possibility to decrease topical steroid therapy and when applicable systemic steroid therapy between M2 and M12 | 12 months | |
Secondary | Transcriptome modifications on whole blood | To evaluate possible transcriptome modifications on whole blood in the context of a collaboration with a team experienced in analysis of cytokine signatures associated with JIA and other inflammatory diseases in children (team directed by V. Pascual in Dallas). | 12 months |
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