Comparative Efficacy and Safety of Adalimumab Versus Mycophenolate Mofetil in Steroid-Dependent Non-Infectious Uveitis

The primary objective of this study is to compare the **efficacy** of adalimumab (administered as 80mg on day 0, followed by 40mg every 14 days from week 1 to week 35 subcutaneously) with that of the standard of care, mycophenolate mofetil (2g/day orally for 36 weeks), in patients with recently active non-infectious intermediate, posterior, and pan-uveitis who are dependent on steroids. This comparison is clinically relevant as it aims to determine a potentially more effective treatment option for managing uveitis, which could lead to improved patient outcomes and reduced reliance on corticosteroids.

Secondary objectives include: - Evaluating the cumulative incidence of treatment failure up to week 55 after inclusion. - Assessing changes in best corrected visual acuity (BCVA, Snellen) from baseline to week 55. - Evaluating changes in ocular inflammation in the anterior chamber and vitreous from baseline to week 55. - Assessing changes in other signs, including vessel leakage, from baseline to week 36. - Evaluating the presence of macular edema from baseline to week 55. - Assessing the quality of life related to uveitis from inclusion to week 55. - Evaluating the steroid sparing effect from baseline to week 55. - Assessing the number and time to relapse of uveitis, and the characteristics of uveitis at worsening from baseline to week 55. - Evaluating the safety of adalimumab and mycophenolate mofetil up to week 55.

The clinical trial involves participants diagnosed with **recently active non-infectious intermediate, posterior, and pan-uveitis**. The study population includes both male and female adults aged 18 years and older. Participants are required to be in general good health, with no evidence of active tuberculosis, active infection, or malignancy as confirmed by chest X-ray or CT scan within 12 weeks prior to inclusion. The trial does not involve a vulnerable population. Participants were selected based on specific inclusion criteria, including a documented medical history of the condition and recent activity of the disease despite steroid dependency. Lifestyle considerations such as contraceptive measures are required for participants with reproductive potential to prevent pregnancy during and after the study. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed as a **randomized**, controlled, multicenter study to evaluate the efficacy and safety of **adalimumab** compared to **mycophenolate mofetil** in patients with steroid-dependent non-infectious uveitis. The trial will follow a two-arm, open-label format with a 1:1 randomization ratio. The primary objective is to assess the treatment failure rate at 36 weeks, with treatment failure defined by specific ocular criteria, including new active inflammatory lesions or worsening of visual acuity. Secondary endpoints include time to treatment failure, changes in visual acuity, and safety assessments up to 55 weeks.

The trial will commence with a screening visit, conducted up to four weeks before the inclusion visit, to verify eligibility based on criteria such as age, diagnosis, and recent activity of non-infectious uveitis. Participants will then proceed to the inclusion/randomization visit, where they will be assigned to receive either adalimumab or mycophenolate mofetil. The study involves multiple follow-up visits at weeks 4, 8, 12, 16, 20, 24, 30, 36, and 55 to monitor efficacy and safety parameters, including visual acuity and anterior chamber cell grade.

The expected duration of participant involvement is approximately 55 weeks, with the trial estimated to conclude by June 2027. Participants may be withdrawn from the study early if they experience treatment failure, defined by specific ocular criteria, or if they require additional immunosuppressive therapy. The trial will ensure adherence to ethical standards, with informed consent obtained from all participants prior to any study-specific procedures. The study aims to provide valuable insights into the management of steroid-dependent non-infectious uveitis, potentially influencing future therapeutic strategies.

The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. **Mycophenolate mofetil** is utilized as a standard-of-care therapy in this study. It is administered in the form of a film-coated tablet, with a dosage of 2 grams per day, taken orally. The treatment period for mycophenolate mofetil is set for 36 weeks, with a maximum total dose of 504 grams. This medication is used to manage steroid-dependent non-infectious uveitis.

**Adalimumab** is the experimental medication being evaluated in this trial. It is provided as a solution for injection in a pre-filled pen, with an initial dose of 80 mg administered subcutaneously on day 0, followed by 40 mg every 14 days from week 1 to week 35. The maximum total dose for adalimumab is 800 mg over the 36-week treatment period. This medication is being tested for its efficacy in treating non-infectious intermediate, posterior uveitis, and pan-uveitis with steroid dependency.

**Rifinah**, containing the active substances **isoniazid** and **rifampicin**, is included as a comparator treatment. It is administered as a coated tablet, with a maximum daily dose of 450 mg. The treatment duration for Rifinah is 3 weeks, with a total maximum dose of 40,950 mg. This medication is used to compare its effects against the experimental treatment.

**Fluorescein sodium** is used as an auxiliary treatment in the form of an injectable solution. The maximum daily dose is 5 ml, with a total maximum dose of 20 ml over a 4-week period. This substance is utilized for diagnostic purposes within the trial.

**Indocyanine green** is another auxiliary treatment, administered as an injection. The maximum daily dose is 2.5 ml, with a total maximum dose of 10 ml over a 4-week period. Similar to fluorescein sodium, indocyanine green is used for diagnostic purposes.

**Prednisolone** is included as a comparator treatment, administered orally. The maximum daily dose is 35 mg, with a total maximum dose of 1,195 mg over a 19-week period. This medication is used to assess its efficacy in comparison to the experimental treatment.

The efficacy of the clinical trial will be assessed through a series of predefined primary and secondary endpoints. The primary efficacy endpoint is the treatment failure rate at 36 weeks. Treatment failure is defined by the occurrence of 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 more than three lines; a two-step increase in anterior chamber cell grade and/or in vitreous haze relative to baseline; absence of steroid discontinuation between week 13 and week 19; or the need for any additional immunosuppressive drug or injectable steroids.

Secondary endpoints include the time to treatment failure up to week 55, Snellen BCVA in each eye at multiple timepoints (week 4, week 8, week 12, week 16, week 20, week 24, week 30, week 36, and week 55), anterior chamber cell grade, and vitreous haze grade (SUN criteria) at the same timepoints. Additional secondary measures include central retinal thickness, the proportion of patients with central macular thickness less than 300 microns, time to optical coherence tomographic (OCT) evidence of macular edema, and the NEI Visual Functioning Questionnaire-25 (VFQ-25) composite score at specific intervals. The study will also evaluate measures of corticosteroid sparing, cumulative incidence of relapse, and the number of relapses up to week 55. Safety and tolerability will be assessed by the frequency and severity of adverse events and treatment discontinuation from baseline to week 55. Furthermore, the percentage of patients without chorioretinal or vascular lesions on retinal angiography will be evaluated up to week 36.