Non Infectious Uveitis
Conditions
Keywords
Non-infectious uveitis, Macular oedema, Retinal vascularitis, Adalimumab, Mycophenolate mofetil
Brief summary
FOCUS is the first prospective randomized study comparing standard of care (mycophenolate mofetil) to adalimumab in recently active non infectious uveitis (NIU) with steroid dependency. There is no firm evidence or randomized trials that compared classical immunosuppressive compounds to biological agents; or identified the best treatment in this condition. The burden of NIU has been reduced with the use of immunosuppressive agents and biologics, raising the question of which of these compounds should be preferentially used in recently active NIU with steroid dependency.
Interventions
DRUGAdalimumab
Adalimumab (80mg at day 0, then 40mg/14 days from W1 to W35 subcutaneously)
DRUGMycophenolate Mofetil
2 g/day orally for 36 weeks
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Provide written, informed consent prior to the performance of any study-specific procedures 2. ≥18 years of age 3. Diagnosis of non-infectious intermediate, posterior-, or pan-uveitis in at least one eye fulfilling the International Study Group Classification Criteria (Standardization of Uveitis Nomenclature \[SUN\] criteria) of posterior, or pan- uveitis confirmed by documented medical history 4. Recent activity of Non Infectious Uveitis as defined by the presence of at least 1 of the following parameters in either eye within the 3 months prior to inclusion visit despite \>7mg/day of oral prednisone: * Active chorioretinal or retinal vascular lesion * Presence of macular edema by optical coherence. * ≥ 2+ anterior chamber cells (Standardization of Uveitis Nomenclature \[SUN\] criteria) * ≥ 2+ vitreous haze (National Eye Institute \[NEI\]/SUN criteria) 5. Chest X-ray (postero-anterior and lateral) or CT-scanner results within 12 weeks prior to inclusion with no evidence of active Tuberculosis, active infection, or malignancy 6. A potential subject with a positive interferon-gamma release assay (IGRA) (e.g., QuantiFERON®-TB Gold or T-spot TB® Test) at inclusion is eligible if: 1. Her/his chest X-ray does not show evidence suggestive of active tuberculosis disease 2. And there are no clinical signs and symptoms of pulmonary and/or extra-pulmonary tuberculosis disease. 3. And these subjects with a latent tuberculosis infection who have not already received a prophylactic tuberculosis treatment must agree in advance to complete such a treatment course. 7. For female subjects of child-bearing potential: a negative pregnancy test at inclusion 8. For subjects with reproductive potential, a willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study and 3 months and 5 months after stopping therapy for Mycophenolate mofetil (MMF) and adalimumab, respectively, unless sterility is confirmed. The simultaneous use of two complementary methods of contraception is preferable. Methods which may be considered as highly effective methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods (according to Clinical Trial Falicitation Group (CTFG) recommendations). Such methods include: For Female subjects : 1. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation 1: * oral * intravaginal * transdermal 2. progestogen-only hormonal contraception associated with inhibition of ovulation: * oral * injectable * implantable 3. intrauterine device (IUD) 4. intrauterine hormone-releasing system (IUS) 5. bilateral tubal occlusion 6. vasectomised partner 7. sexual abstinence (In the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject). For male subjects : 1. use of condoms 2. vasectomy (with documentation of azoospermia) 3. sexual abstinence 9. Affiliated to a social security system
Exclusion criteria
1. Infectious uveitis, masquerade syndromes (idiopathic uveitis is permitted) 2. Isolated anterior uveitis 3. Monocular patient 4. Active tuberculosis 5. Positive HIV serology or Hepatitis C Virus (HCV) Hepatitis B Virus (HBV) Ag test 6. History of malignancy within 5 years prior to Inclusion other than carcinoma in situ of the cervix, non-metastatic squamous or basal cell carcinoma of the skin. 7. History of severe allergic or anaphylactic reactions to monoclonal antibodies, mycophenolate mofetil, rifampicin, isoniazid or fluorescein 8. Infection requiring treatment with intravenous antibiotics within 3 weeks prior to inclusion 9. History of multiple sclerosis and/or demyelinating disorder 10. Laboratory values assessed during inclusion: * Hemoglobin \< 8g/dL * Whole Blood Count (WBC) \< 2.0 x 103/mm3 * Platelet count \< 80 x 103/mm3 * Glomerular filtration rates (GFR) \<30ml/min. * Transaminases \> 3 times upper normal value 11. Use of the following systemic treatments during the specified periods: * Treatment with any systemic alkylating agents within 12 months prior to inclusion (e.g., cyclophosphamide, chlorambucil) * Any live (attenuated) vaccine within 4 weeks prior to inclusion. 12. Stage III and IV New York Heart Association (NYHA) cardiac insufficiency 13. Pregnancy or breastfeeding 14. Under legal protection 15. Participation in another interventional study involving human participants or in the exclusion period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment failure rate | At week 36 | Treatment failure is defined by any of the following in at least one eye: * new active, inflammatory chorioretinal or retinal vascular lesions; * worsening of Best Corrected Visual Acuity (BCVA) by\>3 lines; Score from 20/10 (best vision) to 20/2400 (worst vision). * 2- step increase in anterior chamber cell grade and/or in vitreous haze relative to baseline. Anterior chamber cells scored from 0 (None) to 4+ (intense: fibrin or plastic aquerous) and Vitreous haze Scored from 0 (\<1 cell in field) to +4 (\>100 cells in field) * absence of steroid discontinuation between week 13 and week 19 (as per protocol) * or any additional immunosuppressive drug or injectable steroids |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best corrected visual acuity | At week 4 | Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision). |
| Anterior chamber cell grade in each eye | At week 4 | Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous). |
| Vitreous haze grade in each eye. | At week 4 | Nussenblatt score, Score from 0 (\<1 cell in field) to +4 (\>100 cells in field) |
| Central retinal thickness in each eye from baseline | At week 4 | — |
| Proportion of patients with central macular thickness< 300 microns | At week 4 | — |
| Time to optical coherence tomographic (OCT) evidence of macular edema in at least one eye | Up to week 55 | — |
| Time to treatment failure | Up to week 55 | — |
| Measures of corticosteroid sparing | Up to week 55 | Percent meeting targets \[\<0.1 mg/kg/day prednisone\], mean change, mean dose at week 55, and cumulative dose |
| Cumulative incidence of relapse | Up to week 55 | — |
| Number of relapses | Up to week 55 | — |
| Number of clinical manifestations of underlying disease | Up to week 55 | Depending on the underlying disease |
| Frequency and severity of adverse events | Up to week 55 | — |
| Treatment discontinuation | Up to week 55 | — |
| National Eye Institute Visual Functioning Questionaire-25 (VFQ-25) composite score | At week 12 | Note after responses converted: 100=Best, 0=Worst possible score |
Contacts
Primary ContactBahram BODAGHI, Pr
Backup ContactJérôme Lambert, Pr
Outcome results
None listed