Multi-centre open label clinical trial.
ID
Bron
Verkorte titel
Aandoening
Patients with endogenous uveitis or vasculitis (e.g. sarcoidosis, intermediate uveitis, Behcet’s, idiopathic ocular vasculitis, birdshot and VKH/sympathetic ophthalmia).
Ondersteuning
Einsteinweg 92
2333 CD LEIDEN
The Netherlands
Tel: +31 71 305 3967
Fax: +31 71 5242157
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
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.
Achtergrond van het onderzoek
Patients will not be assigned randomly. All patients will be treated prospectively and will receive infliximab at weeks 0, 2, 6, 14, 22, 30, 38 and 46.
Concomitant systemic:
Immunosuppressants will be tapered starting at week 6 and be completed at week 12, in patients who maintained or improved their visual acuity at week 6 as compared to week 0. The choice of taper will be left to the treating physician, as long as all concomitant systemic immunosuppressants are withdrawn 6 weeks after starting the taper.
An attempt will be made to taper MTX and steroids completely, however a MTX dose up to a maximum of 7.5 mg/week and steroids up to a maximum equivalent dose of 7.5 mg prednisone/day are allowed.
If a patient’s vision acuity worsened while on Infliximab, but did not reach the exit criteria, concomitant immunosuppressants will not be tapered until the vision is equal or better than the baseline vision at week 0. Taper of concomitant immunosuppressants can be started at the latest at week 22.
The exit criteria are reached when the patient has:
1. A drop in visual acuity by 10 or more letters (two lines) on the ETDRS eye chart at a study visit as compared to the previous visit, or more than 10 letters from the baseline vision;
2. An increase in vitreous haze of at least 2 grades from the previous visit (or more than 2 grades from baseline) based on the chart by Nussenblatt et al (17)
3. Evidence of retinal infarction as manifested by new retinal opacification associated with retinal hemorrhage along a retinal artery or vein. The area should measure at least 2 disc diameter;
4. Restarted systemic immunosuppressive therapy or increased the dose of prednisone above 7.5 mg/day or MTX above 7.5 mg/week, as initiated by any physician (whether the investigator or not).
Doel van het onderzoek
Multi-centre open label clinical trial.
Onderzoeksopzet
N/A
Onderzoeksproduct en/of interventie
Infusions with infliximab 5 mg/kg bodyweight monotherapy at weeks 0, 2, 6, 14, 22, 30, 38 and 46.
Publiek
Edith Dijkman, van
Meidoornstraat 72
Almere 1326 DE
The Netherlands
+31 (0)36 5232009
edith@goodclinicalpractice.nl
Wetenschappelijk
Edith Dijkman, van
Meidoornstraat 72
Almere 1326 DE
The Netherlands
+31 (0)36 5232009
edith@goodclinicalpractice.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
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.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
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.
Opzet
Deelname
Opgevolgd door onderstaande (mogelijk meer actuele) registratie
Geen registraties gevonden.
Andere (mogelijk minder actuele) registraties in dit register
Geen registraties gevonden.
In overige registers
Register | ID |
---|---|
NTR-new | NL451 |
NTR-old | NTR491 |
Ander register | : N/A |
ISRCTN | ISRCTN wordt niet meer aangevraagd. |