Treatment FOr Corticosteroid Dependent UveitiS

Phase 3

Not yet recruiting

• Conditions: Non Infectious Uveitis
• Interventions: Drug: Adalimumab; Drug: Mycophenolate Mofetil

• Registration Number: NCT06258915
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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. T...

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Status Verified: 2024-01
• Study First Submitted: 2024-01-23
• Study First Submitted QC: 2024-02-12
• Last Update Submitted: 2024-02-12
• Study First Posted: 2024-02-14
• Last Update Posted: 2024-02-14
• Study Start: 2024-03-01
• Primary Completion: 2027-06-01
• Study Completion: 2027-11-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 120

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Adalimumab	Adalimumab	-
Mycophenolate mofetil	Mycophenolate Mofetil	-

Primary Outcome Measures

Name	Time	Method
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).; ...

Secondary Outcome Measures

Name	Time	Method
Best corrected visual acuity	At week 55	Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).
Central retinal thickness in each eye from baseline	At 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
Anterior chamber cell grade in each eye	At week 55	Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).
Time to treatment failure	Up to week 55
Vitreous haze grade in each eye.	At week 55	Nussenblatt score, Score from 0 (\<1 cell in field) to +4 (\>100 cells in field)
Proportion of patients with central macular thickness< 300 microns	At week 55
Time to optical coherence tomographic (OCT) evidence of macular edema in at least one eye	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 36	Note after responses converted: 100=Best, 0=Worst possible score