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NCT Number: NCT06258915

Treatment FOr Corticosteroid Dependent UveitiS

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.

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Key information

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Provide written, informed consent prior to the performance of any study-specific procedures
  • ≥18 years of age
  • 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
  • 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)
  • 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
  • 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:
  • Her/his chest X-ray does not show evidence suggestive of active tuberculosis disease
  • And there are no clinical signs and symptoms of pulmonary and/or extra-pulmonary tuberculosis disease.
  • 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.
  • For female subjects of child-bearing potential: a negative pregnancy test at inclusion
  • 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 :

  • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation 1:
  • oral
  • intravaginal
  • transdermal
  • progestogen-only hormonal contraception associated with inhibition of ovulation:
  • oral
  • injectable
  • implantable
  • intrauterine device (IUD)
  • intrauterine hormone-releasing system (IUS)
  • bilateral tubal occlusion
  • vasectomised partner
  • 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 :

  • use of condoms
  • vasectomy (with documentation of azoospermia)
  • sexual abstinence
  • Affiliated to a social security system

Exclusion criteria

  • Infectious uveitis, masquerade syndromes (idiopathic uveitis is permitted)
  • Isolated anterior uveitis
  • Monocular patient
  • Active tuberculosis
  • Positive HIV serology or Hepatitis C Virus (HCV) Hepatitis B Virus (HBV) Ag test
  • 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.
  • History of severe allergic or anaphylactic reactions to monoclonal antibodies, mycophenolate mofetil, rifampicin, isoniazid or fluorescein
  • Infection requiring treatment with intravenous antibiotics within 3 weeks prior to inclusion
  • History of multiple sclerosis and/or demyelinating disorder
  • 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
  • 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.
  • Stage III and IV New York Heart Association (NYHA) cardiac insufficiency
  • Pregnancy or breastfeeding
  • Under legal protection
  • Participation in another interventional study involving human participants or in the exclusion period

Treatment and study plan

Adalimumab

Drug

Adalimumab (80mg at day 0, then 40mg/14 days from W1 to W35 subcutaneously)

Mycophenolate mofetil

Drug

2 g/day orally for 36 weeks

Primary outcomes

  1. Treatment failure rate

    Time frame: 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 outcomes

  1. Time to treatment failure

    Time frame: Up to week 55

  2. Best corrected visual acuity

    Time frame: At week 4

    Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).

  3. Best corrected visual acuity

    Time frame: At week 8

    Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).

  4. Best corrected visual acuity

    Time frame: At week 12

    Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).

  5. Best corrected visual acuity

    Time frame: At week 16

    Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).

  6. Best corrected visual acuity

    Time frame: At week 20

    Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).

  7. Best corrected visual acuity

    Time frame: At week 24

    Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).

  8. Best corrected visual acuity

    Time frame: At week 30

    Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).

  9. Best corrected visual acuity

    Time frame: At week 36

    Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).

  10. Best corrected visual acuity

    Time frame: At week 55

    Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).

  11. Anterior chamber cell grade in each eye

    Time frame: At week 4

    Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).

  12. Anterior chamber cell grade in each eye

    Time frame: At week 8

    Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).

  13. Anterior chamber cell grade in each eye

    Time frame: At week 12

    Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).

  14. Anterior chamber cell grade in each eye

    Time frame: At week 16

    Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).

  15. Anterior chamber cell grade in each eye

    Time frame: At week 20

    Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).

  16. Anterior chamber cell grade in each eye

    Time frame: At week 24

    Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).

  17. Anterior chamber cell grade in each eye

    Time frame: At week 30

    Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).

  18. Anterior chamber cell grade in each eye

    Time frame: At week 36

    Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).

  19. Anterior chamber cell grade in each eye

    Time frame: At week 55

    Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).

  20. Vitreous haze grade in each eye.

    Time frame: At week 4

    Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)

  21. Vitreous haze grade in each eye.

    Time frame: At week 8

    Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)

  22. Vitreous haze grade in each eye.

    Time frame: At week 12

    Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)

  23. Vitreous haze grade in each eye.

    Time frame: At week 16

    Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)

  24. Vitreous haze grade in each eye.

    Time frame: At week 20

    Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)

  25. Vitreous haze grade in each eye.

    Time frame: At week 24

    Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)

  26. Vitreous haze grade in each eye.

    Time frame: At week 30

    Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)

  27. Vitreous haze grade in each eye.

    Time frame: At week 36

    Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)

  28. Vitreous haze grade in each eye.

    Time frame: At week 55

    Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)

  29. Central retinal thickness in each eye from baseline

    Time frame: At week 4

  30. Central retinal thickness in each eye from baseline

    Time frame: At week 8

  31. Central retinal thickness in each eye from baseline

    Time frame: At week 12

  32. Central retinal thickness in each eye from baseline

    Time frame: At week 16

  33. Central retinal thickness in each eye from baseline

    Time frame: At week 20

  34. Central retinal thickness in each eye from baseline

    Time frame: At week 24

  35. Central retinal thickness in each eye from baseline

    Time frame: At week 30

  36. Central retinal thickness in each eye from baseline

    Time frame: At week 36

  37. Central retinal thickness in each eye from baseline

    Time frame: At week 55

  38. Proportion of patients with central macular thickness< 300 microns

    Time frame: At week 4

  39. Proportion of patients with central macular thickness< 300 microns

    Time frame: At week 8

  40. Proportion of patients with central macular thickness< 300 microns

    Time frame: At week 12

  41. Proportion of patients with central macular thickness< 300 microns

    Time frame: At week 16

  42. Proportion of patients with central macular thickness< 300 microns

    Time frame: At week 20

  43. Proportion of patients with central macular thickness< 300 microns

    Time frame: At week 24

  44. Proportion of patients with central macular thickness< 300 microns

    Time frame: At week 30

  45. Proportion of patients with central macular thickness< 300 microns

    Time frame: At week 36

  46. Proportion of patients with central macular thickness< 300 microns

    Time frame: At week 55

  47. Time to optical coherence tomographic (OCT) evidence of macular edema in at least one eye

    Time frame: Up to week 55

  48. National Eye Institute Visual Functioning Questionaire-25 (VFQ-25) composite score

    Time frame: At week 12

    Note after responses converted: 100=Best, 0=Worst possible score

  49. National Eye Institute Visual Functioning Questionaire-25 (VFQ-25) composite score

    Time frame: At week 24

    Note after responses converted: 100=Best, 0=Worst possible score

  50. National Eye Institute Visual Functioning Questionaire-25 (VFQ-25) composite score

    Time frame: At week 36

    Note after responses converted: 100=Best, 0=Worst possible score

  51. Measures of corticosteroid sparing

    Time frame: Up to week 55

    Percent meeting targets [<0.1 mg/kg/day prednisone], mean change, mean dose at week 55, and cumulative dose

  52. Cumulative incidence of relapse

    Time frame: Up to week 55

  53. Number of relapses

    Time frame: Up to week 55

  54. Number of clinical manifestations of underlying disease

    Time frame: Up to week 55

    Depending on the underlying disease

  55. Frequency and severity of adverse events

    Time frame: Up to week 55

  56. Treatment discontinuation

    Time frame: Up to week 55

Study contacts

Contact information is provided by the study sponsor or research team.

Bahram BODAGHI, Pr

CONTACT

[email protected]

+33142163728

Jérôme Lambert, Pr

CONTACT

[email protected]

+33142499742

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study title

Randomized Controlled Multicenter Study Comparing Efficacy and Safety of Adalimumab to That of Mycophenolate Mofetil in Steroid Dependent Non-infectious Uveitis

Acronym: FOCUS

Important dates

Study start
2024
Primary completion
2027
Study completion
2027
First posted
Feb 14, 2024
Registry last updated
Feb 14, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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