A Phase III Study to Evaluate the Port Delivery System With Ranibizumab Compared With Monthly Ranibizumab Injections in Participants With Wet Age-Related Macular Degeneration

Hoffmann-La Roche415 enrolled

Overview

Study GR40548 is a Phase III, randomized, multicenter, open-label (visual assessor \[VA\]-masked), active-comparator study designed to assess the efficacy, safety, and pharmacokinetics (PK) of 100mg/ml delivered via the Port Delivery System with ranibizumab (PDS) compared with ranibizumab intravitreal injections at 0.5 mg (10 mg/mL) in participants with neovascular age-related macular degeneration (nAMD).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

415

Conditions

Neovascular Age-Related Macular Degeneration

Interventions

PDS Implant filled with 100 mg/mL Ranibizumab

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥50 years, at time of signing Informed Consent Form * Initial diagnosis of exudative neovascular age-related macular degeneration (nAMD) within 9 months prior to the screening visit * Previous treatment with at least three anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections for nAMD per standard of care within 6 months prior to the screening visit * Demonstrated response to prior anti-VEGF intravitreal treatment since diagnosis * Best-corrected visual acuity (BCVA) of 34 letters or better Exclusion Criteria: * Subfoveal fibrosis or subfoveal atrophy in study eye * Subretinal hemorrhage that involves the center of the fovea in study eye * History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in study eye * Prior treatment with Visudyne®, external-beam radiation therapy, or transpupillary thermotherapy in study eye * Previous intraocular device implantation in study eye * Previous laser (any type) used for AMD treatment in study eye * Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit in either eye * Prior participation in a clinical trial involving anti-VEGF drugs within 6 months prior to the randomization visit, other than ranibizumab in either eye * CNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia in either eye * Uncontrolled blood pressure * History of stroke within the last 3 months prior to informed consent * Uncontrolled atrial fibrillation within 3 months of informed consent * History of myocardial infarction within the last 3 months prior to informed consent * History of other disease, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the Implant and that might affect interpretation of the results of the study or renders the participant at high risk of treatment complications in the opinion of the investigator * Current systemic treatment for a confirmed active systemic infection * Chronic use of oral corticosteroids * Active cancer within 12 months of randomization * Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent (excluding vitamins and minerals)

Locations (77)

Barnet Dulaney Perkins Eye Center

Mesa, Arizona, United States

Associated Retina Consultants

Phoenix, Arizona, United States

Arizona Retina and Vitreous Consultants

Phoenix, Arizona, United States

Retinal Consultants of Arizona

Phoenix, Arizona, United States

California Retina Consultants

Bakersfield, California, United States

Outcomes

Primary Outcomes

Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score at the Average of Week 36 and Week 40, as Assessed Using the ETDRS Visual Acuity Chart at a Starting Distance of 4 Meters

The primary efficacy endpoint is the change in BCVA score from baseline averaged over Weeks 36 and 40 with BCVA assessed using the ETDRS chart at a starting distance of 4 meters. ETDRS = Early Treatment Diabetic Retinopathy Study. The primary objective is to determine the NI and equivalence between the two treatment groups, as measured by the primary efficacy endpoint with a NI margin of 4.5 letters and equivalence margins of ± 4.5 letters. A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.

Time frame: Baseline, and the average of Week 36 and Week 40

Secondary Outcomes

Change From Baseline in BCVA Score Averaged Over Week 60 and Week 64

Time frame: Baseline, Week60, Week 64

Change From Baseline in BCVA Score Over Time

Time frame: Baseline up to Week 96

Percentage of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse at the Average Over Week 36 and Week 40

Time frame: Baseline, and the average of Week 36 and Week 40

Percentage of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Over Time

Time frame: Baseline up to Week 96

Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better at the Average Over Week 36 and Week 40

Time frame: Baseline, and the average of Week 36 and Week 40

Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Over Time

Time frame: Baseline up to Week 96

Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40

Time frame: Baseline, and the average of Week 36 and Week 40

Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline Over Time

Time frame: Baseline up to Week 96

Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40

Time frame: Baseline up to Week 40

Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline Over Time

Time frame: Baseline up to Week 96

Change From Baseline in Center Point Thickness (CPT) at Week 36

Time frame: Baseline to Week 36

Change From Baseline in CPT Over Time

Time frame: Baseline up to Week 96

Percentage of Participants in the PDS Implant Arm Who Undergo Supplemental Treatment With Intravitreal Ranibizumab 0.5 mg Before the First, Second, Third, and Fourth Fixed Refill-Exchange Intervals

Time frame: Day 1 to Week 24, Week 25 to Week 48, Week 49 to Week 72, Week73 to Week 96

Percentage of Participants in the PDS Implant Arm Who Undergo a Supplemental Treatment That Requires Subsequent Additional Supplemental Treatments During the Study

Time frame: Week 16 to Week 92

Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs