Evaluation of Ranibizumab Port Delivery System Refill Regimen in Neovascular Age-Related Macular Degeneration: A Phase IIIb, Multicenter, Single-Arm Study

The primary objective of this study is to evaluate the **effectiveness** of the Port Delivery System with ranibizumab (PDS) administered every 36 weeks in patients with Neovascular Age-Related Macular Degeneration (nAMD). This is clinically relevant as it aims to assess the long-term efficacy of a novel delivery system for ranibizumab, potentially offering a sustained treatment option for nAMD, which could improve patient outcomes and reduce the frequency of intravitreal injections.

Secondary objectives include:

• Evaluating the effectiveness of PDS Q36W based on additional functional and anatomical outcomes.
• Assessing the treatment and visit burden associated with PDS Q36W.
• Evaluating the Patient Reported Outcomes (PROs) of PDS Q36W.
• Assessing the safety of PDS.
• Evaluating the device and procedure-related safety.

The clinical trial involves a total of **86 participants** diagnosed with **Neovascular Age-Related Macular Degeneration (nAMD)**. The study population includes both male and female subjects aged **50 years and older**. Participants were selected based on specific criteria, including an initial diagnosis of nAMD within 24 months prior to the screening visit and a demonstrated response to prior anti-vascular endothelial growth factor (VEGF) intravitreal treatment. The trial population is characterized by nAMD disease stability as detected by optical coherence tomography (OCT) and a Best-Corrected Visual Acuity (BCVA) of 34 letters or better. The study includes individuals with available historical OCT image data obtained at or after nAMD diagnosis and prior to the first anti-VEGF treatment. The trial does not specify any particular lifestyle considerations such as diet or physical activity. Both vulnerable and non-vulnerable populations are included in the study.

The clinical trial is designed to evaluate the **effectiveness** and safety of the Port Delivery System with **ranibizumab** in patients with **neovascular age-related macular degeneration** (nAMD). This is a Phase IIIb, multicenter, single-arm study with a primary objective to assess the effectiveness of the Port Delivery System administered every 36 weeks. The trial is expected to commence recruitment on September 1, 2025, and conclude by October 12, 2028. Participants will be involved in the study for a duration of up to 72 weeks, with the possibility of early termination if they do not meet the inclusion criteria or if adverse events occur.

The trial will include a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age (≥ 50 years), initial diagnosis of nAMD within 24 months, and demonstrated response to prior anti-VEGF treatment. Following the screening, participants will undergo a baseline assessment, including best-corrected visual acuity (BCVA) measurements. Subsequent visits will occur at regular intervals to monitor changes in BCVA and other secondary endpoints, such as center point thickness and central subfield thickness, up to and including Week 72.

The study design incorporates a single-arm approach, with all participants receiving the investigational treatment. The primary endpoint is the change from baseline in BCVA score, averaged over Weeks 68 and 72. Secondary endpoints include the proportion of patients experiencing specific changes in BCVA, the frequency of study visits, and the incidence of adverse events. The trial will also assess patient preferences for the Port Delivery System compared to intravitreal treatment, using the PDS Patient Preference Questionnaire at Weeks 24 and 72.

Participants will be required to attend follow-up visits to ensure the stability of nAMD and to monitor for any adverse events. The end-of-study visit will involve a comprehensive assessment of the participant's condition and the collection of final data. Conditions that may lead to early termination from the study include significant adverse events or failure to adhere to the study protocol. The trial aims to provide valuable insights into the long-term management of nAMD using the Port Delivery System with **ranibizumab**.

The clinical trial involves the use of two experimental medications, both containing the active substance **ranibizumab**. The first medication is **Lucentis 10 mg/ml solution for injection in pre-filled syringe**, manufactured by Novartis Europharm Limited. This pharmaceutical form is a solution for injection, specifically designed for **intravitreal use**. The dosage is set at a maximum of 2 mg per administration, with a total maximum dose of 12 mg over the course of the treatment. The treatment period extends up to 144 weeks. Lucentis is administered as a combination product that includes a device, ensuring precise delivery of the medication.

The second experimental medication is **RO4893594**, also known as Susvimo, produced by F. Hoffmann-La Roche Ltd. This medication is provided as a solution for injection and is administered via the **Port Delivery System** for intravitreal use. The maximum dosage per administration is 2 mg, with a total maximum dose of 8 mg over a treatment period of 19 weeks. Similar to Lucentis, RO4893594 is a combination product that includes a device, facilitating the controlled release of the medication. The Port Delivery System is specifically designed to maintain therapeutic levels of ranibizumab over an extended period, reducing the frequency of intravitreal injections.

Both medications are integral to the study, which aims to evaluate the effectiveness, safety, and patient-reported outcomes of a 36-week refill exchange regimen for the Port Delivery System with ranibizumab in patients with neovascular age-related macular degeneration. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol.

The efficacy of the Port Delivery System with **ranibizumab** in patients with neovascular age-related macular degeneration will be assessed through a series of primary and secondary endpoints. The primary endpoint is the change from baseline in best-corrected visual acuity (BCVA) score, measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters, averaged over Weeks 68 and 72. Secondary endpoints include the change from baseline in BCVA score over time up to and including Week 72, the proportion of patients who lose ≤ 15, ≤ 10, ≤ 5, or gain ≥ 0 letters in BCVA score from baseline over time, and changes in center point thickness (CPT) and central subfield thickness (CST) over time up to and including Week 72.

Additional secondary endpoints involve the proportion of participants who do not undergo supplemental treatment with intravitreal (IVT) ranibizumab 0.5 mg before each refill-exchange procedure and overall up to and including Week 72, the number of supplemental treatments with IVT ranibizumab 0.5 mg received in each refill cycle and overall, and the frequency of study visits in each refill cycle and overall up to and including Week 72. Patient preferences will also be evaluated using the PDS Patient Preference Questionnaire (PPPQ) at Weeks 24 and 72, assessing the proportion of patients who report preferring ranibizumab 100 mg/mL delivered via the PDS compared with IVT treatment. The incidence and severity of ocular and systemic adverse events, as well as adverse device effects, will be monitored throughout the trial.