Patients with endogenous uveitis or vasculitis (e.g. sarcoidosis, intermediate uveitis, Behcet’s, idiopathic ocular vasculitis, birdshot and VKH/sympathetic ophthalmia).
Conditions
Interventions
Infusions with infliximab 5 mg/kg bodyweight monotherapy at weeks 0, 2, 6, 14, 22, 30, 38 and 46.
Sponsors
AMC Medical Research B.V., Prof. Dr. M.D. de Smet, Meibergdreef 9, 1105 AZ AMSTERDAM ZO, The Netherlands, +31 20 566 34 59
Eligibility
Inclusion criteria
Inclusion criteria: 1. Men or women 18 years of age with non-infectious bilateral sight-threatening uveitis due to one of the inflammatory conditions listed below: a. Ocular sarcoidosis; b. Intermediate uveitis; c. Behcet's syndrome; d. Idiopathic Retinal Vasculitis where systemic or infectious causes have been eliminated. In particular patients will not have evidence of Wegener¡¯s granulomatosis, SLE, PAN, polymyositis, dermatomyositis or other systemic vasculitic disorder; e. Birdshot; 2. Patients must be taking a minimum of 0.5 mg/kg bodyweight/day of prednisone, cyclosporine or other immunomodulatory agent (mycophenolate, tacrolimus, sirolimus, interferon therapy (in the case of Behçet¡¯s disease), anti-metabolites, or any combination of these for the treatment of their intraocular inflammatory disease, for at least three months; 3. Disease that is 24 months or less in duration, or a patient with a significant flare in the past 24 months requiring intensification of anti-inflammatory therapy; 4. Visual acuity of 0.1 or better in at least one eye. Complete control of intraocular inflammation is not necessary; 5. Men and women of childbearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) for the duration of the study and should continue such precautions for 6 months after receiving the last infusion; 6. The screening laboratory test results must meet the following criteria: a. Hemoglobin ³ 8.5 g/dL; b. WBC ³ 3.5 x 109/L; c. Neutrophils ³ 1.5 x 109/L; d. Platelets ³ 100 x 109/L; e. SGOT (AST) and alkaline phosphatase levels must be within 3 times the upper limit of normal range for the laboratory conducting the test; 7. Must have a chest radiograph within 3 months prior to first infusion with no evidence of malignancy, infection or fibrosis suggestive of a [previous] TB infection; 8. Patient must be able to adhere to the study visit schedule and other protocol requirements; 9. The patient must be capable of giving informed consent and the consent must be obtained prior to any screening procedures.
Exclusion criteria
Exclusion criteria: 1. Inability to visualize the fundus due to corneal or lenticular opacities; 2. Patients requiring ocular surgery within the initial 3 months of treatment, or who have had surgery in the prior 3 months; 3. Women who are pregnant, nursing, or planning pregnancy within 1.5 years after screening (i.e., approximately 6 months following last infusion); 4. Use of any investigational drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer; 5. Treatment with any other therapeutic agent targeted at reducing TNF (e.g., pentoxifylline, thalidomide, etanercept, etc.) within 3 months of screening; 6. Previous administration of infliximab; 7. History of receiving human/murine recombinant products or known allergy to murine products; 8. Serious infections (such as pneumonia or pyelonephritis) in the previous 3 months. Less serious infections (such as acute upper respiratory tract infection [colds] or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator; 9. Documented HIV infection; 10. Have active TB or have evidence of latent TB; 11. Patients with opportunistic infections; 12. Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease; 13. Concomitant congestive heart failure, including medically controlled asymptomatic patients; 14. Any sign and symptom suggestive for a demyelinating disorder; 15. Evidence on T1/T2 weighed MRI of the cerebrum for a demyelinating disorder in patients with intermediate uveitis, within 2 years prior to first infusion and not before the onset of signs and symptoms of intermediate uveitis; 16. Presence of a transplanted organ (with the exception of a corneal transplant > 3 months prior to screening); 17. Malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence); 18. History of lymphoproliferative disease including lymphoma; 19. Known recent substance abuse (drug or alcohol); 20. Poor tolerability of venipuncture or lack of adequate venous access for required blood sampling during the study period.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine if infliximab 5 mg/kg bodyweight monotherapy at weeks 0, 2, 6, 14, 22, 30, 38 and 46 can allow patients with endogenous uveitis or vasculitis unresponsive to standard therapy, to taper their concomitant immunosuppressants, while maintaining or improving their visual acuity and not meet any of the exit criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To Determine the number of weeks patients maintain their visual acuity and not meet any of the exit criteria, after infliximab discontinuation at week 46, in patients who did taper their concomitant immunosuppressants and in patients who did not taper their concomitant immunosuppressants; 2. Determine the percentage of patients who meet the exit criteria during the first 46 weeks and during follow-up, in patients who did taper their concomitant immunosuppressants and in patients who did not taper their concomitant immunosuppressants; 3. Determine the effect of infliximab on quality of life, as assessed by the SF-36; 4. Determine the effect of infliximab on the quality of vision as assessed by the NEI-VFQ-25; 5. Safety of infliximab. | — |
Contacts
Public ContactEdith Dijkman, van
Meidoornstraat 72
Outcome results
None listed