Treatment FOr Corticosteroid Dependent UveitiS

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Adalimumab
  Adalimumab (80mg at day 0, then 40mg/14 days from W1 to W35 subcutaneously)
• Препарат Mycophenolate Mofetil
  2 g/day orally for 36 weeks

Первичные конечные точки

• Treatment failure rate [Срок оценки: At week 36]

Вторичные конечные точки (12)

• Time to treatment failure [Срок оценки: Up to week 55]
• Best corrected visual acuity [Срок оценки: At week 4]
• Best corrected visual acuity [Срок оценки: At week 8]
• Best corrected visual acuity [Срок оценки: At week 12]
• Best corrected visual acuity [Срок оценки: At week 16]
• Best corrected visual acuity [Срок оценки: At week 20]
• Best corrected visual acuity [Срок оценки: At week 24]
• Best corrected visual acuity [Срок оценки: At week 30]
• Best corrected visual acuity [Срок оценки: At week 36]
• Best corrected visual acuity [Срок оценки: At week 55]
• Anterior chamber cell grade in each eye [Срок оценки: At week 4]
• Anterior chamber cell grade in each eye [Срок оценки: At week 8]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06258915 · APHP211032

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗