Clinical trial NCT06258915: Treatment FOr Corticosteroid Dependent UveitiS
Official title: Randomized Controlled Multicenter Study Comparing Efficacy and Safety of Adalimumab to That of Mycophenolate Mofetil in Steroid Dependent Non-infectious Uveitis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Non Infectious Uveitis
Keywords: Non-infectious uveitis
Macular oedema
Retinal vascularitis
Adalimumab
Mycophenolate mofetil
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-02-14
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Treatment failure rate
timeFrame: At week 36
Secondary outcomes:
measure: Time to treatment failure
timeFrame: Up to week 55
measure: Best corrected visual acuity
timeFrame: At week 4
measure: Best corrected visual acuity
timeFrame: At week 8
measure: Best corrected visual acuity
timeFrame: At week 12
measure: Best corrected visual acuity
timeFrame: At week 16
measure: Best corrected visual acuity
timeFrame: At week 20
measure: Best corrected visual acuity
timeFrame: At week 24
measure: Best corrected visual acuity
timeFrame: At week 30
measure: Best corrected visual acuity
timeFrame: At week 36
measure: Best corrected visual acuity
timeFrame: At week 55
measure: Anterior chamber cell grade in each eye
timeFrame: At week 4
measure: Anterior chamber cell grade in each eye
timeFrame: At week 8
measure: Anterior chamber cell grade in each eye
timeFrame: At week 12
measure: Anterior chamber cell grade in each eye
timeFrame: At week 16
measure: Anterior chamber cell grade in each eye
timeFrame: At week 20
measure: Anterior chamber cell grade in each eye
timeFrame: At week 24
measure: Anterior chamber cell grade in each eye
timeFrame: At week 30
measure: Anterior chamber cell grade in each eye
timeFrame: At week 36
measure: Anterior chamber cell grade in each eye
timeFrame: At week 55
measure: Vitreous haze grade in each eye.
timeFrame: At week 4
measure: Vitreous haze grade in each eye.
timeFrame: At week 8
measure: Vitreous haze grade in each eye.
timeFrame: At week 12
measure: Vitreous haze grade in each eye.
timeFrame: At week 16
measure: Vitreous haze grade in each eye.
timeFrame: At week 20
measure: Vitreous haze grade in each eye.
timeFrame: At week 24
measure: Vitreous haze grade in each eye.
timeFrame: At week 30
measure: Vitreous haze grade in each eye.
timeFrame: At week 36
measure: Vitreous haze grade in each eye.
timeFrame: At week 55
measure: Central retinal thickness in each eye from baseline
timeFrame: At week 4
measure: Central retinal thickness in each eye from baseline
timeFrame: At week 8
measure: Central retinal thickness in each eye from baseline
timeFrame: At week 12
measure: Central retinal thickness in each eye from baseline
timeFrame: At week 16
measure: Central retinal thickness in each eye from baseline
timeFrame: At week 20
measure: Central retinal thickness in each eye from baseline
timeFrame: At week 24
measure: Central retinal thickness in each eye from baseline
timeFrame: At week 30
measure: Central retinal thickness in each eye from baseline
timeFrame: At week 36
measure: Central retinal thickness in each eye from baseline
timeFrame: At week 55
measure: Proportion of patients with central macular thickness< 300 microns
timeFrame: At week 4
measure: Proportion of patients with central macular thickness< 300 microns
timeFrame: At week 8
measure: Proportion of patients with central macular thickness< 300 microns
timeFrame: At week 12
measure: Proportion of patients with central macular thickness< 300 microns
timeFrame: At week 16
measure: Proportion of patients with central macular thickness< 300 microns
timeFrame: At week 20
measure: Proportion of patients with central macular thickness< 300 microns
timeFrame: At week 24
measure: Proportion of patients with central macular thickness< 300 microns
timeFrame: At week 30
measure: Proportion of patients with central macular thickness< 300 microns
timeFrame: At week 36
measure: Proportion of patients with central macular thickness< 300 microns
timeFrame: At week 55
measure: Time to optical coherence tomographic (OCT) evidence of macular edema in at least one eye
timeFrame: Up to week 55
measure: National Eye Institute Visual Functioning Questionaire-25 (VFQ-25) composite score
timeFrame: At week 12
measure: National Eye Institute Visual Functioning Questionaire-25 (VFQ-25) composite score
timeFrame: At week 24
measure: National Eye Institute Visual Functioning Questionaire-25 (VFQ-25) composite score
timeFrame: At week 36
measure: Measures of corticosteroid sparing
timeFrame: Up to week 55
measure: Cumulative incidence of relapse
timeFrame: Up to week 55
measure: Number of relapses
timeFrame: Up to week 55
measure: Number of clinical manifestations of underlying disease
timeFrame: Up to week 55
measure: Frequency and severity of adverse events
timeFrame: Up to week 55
measure: Treatment discontinuation
timeFrame: Up to week 55
Other outcomes:
Locations:
Study officials:
References: