Phase III Randomized Double‑Masked Sham‑Controlled Trial of Intravitreal IL6‑Mab in Patients with Uveitic Macular Edema

The primary objective of this study is to evaluate the **efficacy** of RO7200220 on best corrected visual acuity (BCVA) functional outcome compared with sham in patients with **uveitic macular edema**. This is clinically relevant as BCVA is a critical measure of visual function, and improvements in BCVA can significantly impact the quality of life for patients suffering from this condition.

Secondary objectives include:

• Evaluating the efficacy of RO7200220 on BCVA functional outcome at Week 20, 8 weeks after the final study drug dose, compared with sham.
• Assessing the efficacy of RO7200220 on mean BCVA functional outcomes compared with sham.
• Evaluating the efficacy of RO7200220 on mean anatomical outcomes, specifically changes in central subfield thickness (CST), compared with sham.
• Assessing the safety of RO7200220 compared with sham, and specifically in the study eye compared with the fellow eye.
• Characterizing the pharmacokinetics and aqueous humor pharmacodynamics (IL-6) of RO7200220.
• Investigating the formation of serum anti-drug antibodies (ADAs) and evaluating their potential effects.
• Evaluating the efficacy of RO7200220 on additional functional, anatomical, and participant-reported outcomes compared with sham.

The clinical trial investigating the efficacy of RO7200220 on best corrected visual acuity (BCVA) in patients with **Uveitic Macular Edema** includes a total of 179 participants. The study population comprises both male and female subjects, with an age range that includes adults and older adults. Participants were selected based on specific criteria, including a diagnosis of macular edema associated with non-infectious uveitis (NIU), confirmed by spectral-domain optical coherence tomography (SD-OCT). The trial includes individuals with active or inactive, acute, or chronic NIU of any etiology and anatomical type, as assessed by the investigator. The study population is characterized by a best corrected visual acuity (BCVA) letter score ranging from 73 to 19 letters on Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts. The trial also involves a vulnerable population, although specific lifestyle considerations such as diet or physical activity are not detailed in the available data.

The clinical trial is a **Phase III**, multicenter, randomized, double-masked, sham-controlled study designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of RO7200220, a **humanised IgG2 monoclonal antibody against interleukin-6**, administered intravitreally in patients with **uveitic macular edema**. The trial aims to assess the impact of the treatment on best corrected visual acuity (BCVA) compared to a sham procedure. The study is expected to conclude by June 2025, with recruitment having commenced in February 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as macular thickening and BCVA letter score. Following randomization, participants will receive the investigational product or sham treatment according to the study protocol. The primary endpoint is the proportion of participants achieving a ≥15 letter improvement in BCVA at Week 16. Secondary endpoints include changes in BCVA and central subfield thickness (CST) at various time points, as well as the incidence of adverse events and pharmacokinetic measurements.

The trial involves multiple follow-up visits to monitor efficacy and safety, with key assessments at Weeks 16, 20, and 52. The end-of-study visit will occur at the conclusion of the participant's involvement, which is anticipated to last up to 52 weeks. Participants may be withdrawn from the study early due to reasons such as adverse events, non-compliance with the protocol, or withdrawal of consent. The study is structured to ensure rigorous data collection and analysis, maintaining the integrity of the trial outcomes.

The clinical trial involves the administration of **IL6-Mab**, a **solution for injection** containing a **humanised IgG2 monoclonal antibody against interleukin-6**. This experimental medication is provided by F. Hoffmann-La Roche Ltd and is identified by the sponsor product codes RO 720-0220/F12-01 and RO 720-0220/F13-01. The pharmaceutical form of IL6-Mab is a solution for injection, specifically designed for **intravitreal use**. The dosing regimen for IL6-Mab involves a maximum daily dose of 1 mg, with a total maximum dose of 12 mg over a treatment period of 48 weeks. The administration schedule is structured to ensure optimal therapeutic outcomes while monitoring participant compliance throughout the study.

In addition to the experimental treatment, the study employs a **sham-controlled** approach to evaluate the efficacy of IL6-Mab. The sham procedure serves as a comparator treatment, allowing for a rigorous assessment of the drug's impact on best corrected visual acuity (BCVA) in patients with **uveitic macular edema**. The sham control is designed to mimic the administration process without delivering the active medication, thereby maintaining the double-masked nature of the trial. This approach ensures that any observed effects can be attributed to the active treatment rather than placebo effects or procedural biases.

The efficacy of the investigational product, RO7200220, in patients with **uveitic macular edema** will be assessed primarily through the improvement in best corrected visual acuity (BCVA). The primary endpoint is the proportion of participants achieving a ≥15 letter improvement from baseline in BCVA at Week 16. Secondary endpoints include the proportion of participants with a ≥15 letter improvement in BCVA at Week 20 and Week 52, changes from baseline in BCVA scores at Weeks 16, 20, and 52, and changes in central subfield thickness (CST) at the same timepoints. Additional secondary endpoints involve the resolution of uveitic macular edema (UME), changes in the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) composite score, and the incidence and severity of ocular and non-ocular adverse events.

Measurements will be conducted using validated scales and tools, such as the Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts for BCVA assessment. The study will also monitor pharmacokinetics by measuring the concentration of RO7200220 in aqueous humor (AH) and serum over time, as well as the incidence and titer of anti-drug antibodies (ADAs) to RO7200220. The relationship between ADA status and efficacy, safety, and pharmacokinetic/pharmacodynamic endpoints will be evaluated. The study is designed to provide comprehensive data on the efficacy of RO7200220, with assessments scheduled at multiple timepoints throughout the trial duration, including Weeks 16, 20, and 52.