Neovascular Age-Related Macular Degeneration
Conditions
Brief summary
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).
Interventions
DRUGPDS Implant filled with 100 mg/mL Ranibizumab
Will be administered as per the schedule described in individual arm.
DRUGIntravitreal Injections of 10 mg/mL Ranibizumab
Will be administered as per the schedule described in individual arm.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline, and the average of Week 36 and Week 40 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in BCVA Score Over Time | 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 | 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 | 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 | 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 | 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 | 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 | 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 | Baseline up to Week 40 | — |
| Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline Over Time | Baseline up to Week 96 | — |
| Change From Baseline in Center Point Thickness (CPT) at Week 36 | Baseline to Week 36 | — |
| Change From Baseline in BCVA Score Averaged Over Week 60 and Week 64 | Baseline, Week60, Week 64 | — |
| 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 | 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 | Week 16 to Week 92 | — |
| Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs | Randomization to Week 96 | — |
| Percentage of Participants With Adverse Events of Special Interest | Randomization to Week 96 | Percentage of Participants with Adverse Events of Special Interest |
| Observed Serum Ranibizumab Concentrations at Specified Timepoints | Randomization to Week 96 | — |
| Estimated PK Parameter Values AUC0-6M | Randomization to Week 96 | AUC0-6M = Area Under the Concentration-Time Curve From 0 to 6 Months |
| Estimated PK Parameter Value t1/2 After PDS Implant Insertion | Randomization to Week 96 | Apparent terminal half-life |
| Estimated PK Parameter Value Cmin | Randomization to Week 96 | Cmin = Minimum Serum Concentration |
| Estimated PK Parameter Value Cmax | Randomization to Week 96 | Cmax = Maximum Serum Concentration |
| Baseline Prevalence and Incidence of Treatment-Emergent ADA | Randomization to Week 96 | — |
| Change From Baseline in CPT Over Time | Baseline up to Week 96 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PDS Implant Arm Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals | 248 |
| Intravitreal Arm Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter. | 167 |
| Total | 415 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Death | 8 | 4 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Non-Compliance With Study Drug | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 7 |
Baseline characteristics
| Characteristic | PDS Implant Arm | Intravitreal Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 222 Participants | 150 Participants | 372 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 17 Participants | 43 Participants |
| Age, Continuous | 75.2 Years STANDARD_DEVIATION 8.11 | 74.8 Years STANDARD_DEVIATION 7.63 | 75.0 Years STANDARD_DEVIATION 7.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 8 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 240 Participants | 159 Participants | 399 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) White | 240 Participants | 161 Participants | 401 Participants |
| Sex: Female, Male Female | 145 Participants | 100 Participants | 245 Participants |
| Sex: Female, Male Male | 103 Participants | 67 Participants | 170 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 167 | 8 / 248 |
| other Total, other adverse events | 58 / 167 | 225 / 248 |
| serious Total, serious adverse events | 39 / 167 | 78 / 248 |
Outcome results
Primary
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| PDS Implant Arm | 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 | 0.2 letters |
| Intravitreal Arm | 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 | 0.5 letters |
Secondary
Baseline Prevalence and Incidence of Treatment-Emergent ADA
Time frame: Randomization to Week 96
Population: The Biomarker Analysis Population consists of patients who are in the Safety Population and have sufficient data to enable assessment of potential changes in biomarkers in response to treatment during the conduct of this study. The analysis will group patients according to treatment actually received
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PDS Implant Arm | Baseline Prevalence and Incidence of Treatment-Emergent ADA | Patients with a positive sample at time of entry into the study | 5 Participants |
| PDS Implant Arm | Baseline Prevalence and Incidence of Treatment-Emergent ADA | Patients with no positive samples at time of entry into the study | 238 Participants |
| PDS Implant Arm | Baseline Prevalence and Incidence of Treatment-Emergent ADA | Post-baseline Patients Positive for ADA | 38 Participants |
| PDS Implant Arm | Baseline Prevalence and Incidence of Treatment-Emergent ADA | Treatment-induced ADA | 33 Participants |
| PDS Implant Arm | Baseline Prevalence and Incidence of Treatment-Emergent ADA | Treatment-enhanced ADA | 0 Participants |
| PDS Implant Arm | Baseline Prevalence and Incidence of Treatment-Emergent ADA | Treatment unaffected or reduced | 5 Participants |
| PDS Implant Arm | Baseline Prevalence and Incidence of Treatment-Emergent ADA | Patients negative for ADA at all times in the study | 209 Participants |
| Intravitreal Arm | Baseline Prevalence and Incidence of Treatment-Emergent ADA | Patients with a positive sample at time of entry into the study | 8 Participants |
| Intravitreal Arm | Baseline Prevalence and Incidence of Treatment-Emergent ADA | Treatment-enhanced ADA | 2 Participants |
| Intravitreal Arm | Baseline Prevalence and Incidence of Treatment-Emergent ADA | Patients with no positive samples at time of entry into the study | 154 Participants |
| Intravitreal Arm | Baseline Prevalence and Incidence of Treatment-Emergent ADA | Patients negative for ADA at all times in the study | 144 Participants |
| Intravitreal Arm | Baseline Prevalence and Incidence of Treatment-Emergent ADA | Post-baseline Patients Positive for ADA | 21 Participants |
| Intravitreal Arm | Baseline Prevalence and Incidence of Treatment-Emergent ADA | Treatment unaffected or reduced | 6 Participants |
| Intravitreal Arm | Baseline Prevalence and Incidence of Treatment-Emergent ADA | Treatment-induced ADA | 15 Participants |
Secondary
Change From Baseline in BCVA Score Averaged Over Week 60 and Week 64
Time frame: Baseline, Week60, Week 64
Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
| Arm | Measure | Value (MEAN) |
|---|---|---|
| PDS Implant Arm | Change From Baseline in BCVA Score Averaged Over Week 60 and Week 64 | -0.4 letters |
| Intravitreal Arm | Change From Baseline in BCVA Score Averaged Over Week 60 and Week 64 | -0.8 letters |
Secondary
Change From Baseline in BCVA Score Over Time
Time frame: Baseline up to Week 96
Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 72 | -0.3 letters | Standard Deviation 0.64 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 8 | -1.7 letters | Standard Deviation 0.41 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 12 | -0.4 letters | Standard Deviation 0.39 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 16 | -0.6 letters | Standard Deviation 0.41 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 20 | -0.3 letters | Standard Deviation 0.42 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 24 | -0.6 letters | Standard Deviation 0.47 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 28 | -0.1 letters | Standard Deviation 0.47 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 32 | 0.2 letters | Standard Deviation 0.49 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 36 | 0.2 letters | Standard Deviation 0.47 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 40 | 0.2 letters | Standard Deviation 0.51 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 44 | -0.1 letters | Standard Deviation 0.53 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 48 | 0.0 letters | Standard Deviation 0.53 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 52 | 0.1 letters | Standard Deviation 0.54 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 56 | 0.1 letters | Standard Deviation 0.56 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 60 | -0.5 letters | Standard Deviation 0.58 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 64 | -0.3 letters | Standard Deviation 0.59 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 68 | -0.5 letters | Standard Deviation 0.64 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 76 | -1.0 letters | Standard Deviation 0.68 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 80 | -0.7 letters | Standard Deviation 0.64 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 84 | -0.8 letters | Standard Deviation 0.62 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 88 | -1.3 letters | Standard Deviation 0.62 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 92 | -0.9 letters | Standard Deviation 0.63 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 96 | -1.1 letters | Standard Deviation 0.68 |
| PDS Implant Arm | Change From Baseline in BCVA Score Over Time | Week 4 | -4.3 letters | Standard Deviation 0.47 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 76 | 0.2 letters | Standard Deviation 0.83 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 4 | -0.4 letters | Standard Deviation 0.58 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 52 | -0.8 letters | Standard Deviation 0.67 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 8 | 0.1 letters | Standard Deviation 0.51 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 88 | 0.0 letters | Standard Deviation 0.76 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 12 | 0.6 letters | Standard Deviation 0.48 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 56 | -0.5 letters | Standard Deviation 0.67 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 16 | 0.2 letters | Standard Deviation 0.5 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 80 | -0.2 letters | Standard Deviation 0.79 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 20 | 0.1 letters | Standard Deviation 0.52 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 60 | -0.8 letters | Standard Deviation 0.71 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 24 | 0.8 letters | Standard Deviation 0.57 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 96 | -1.3 letters | Standard Deviation 0.84 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 28 | 0.5 letters | Standard Deviation 0.57 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 64 | -0.7 letters | Standard Deviation 0.72 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 32 | 0.9 letters | Standard Deviation 0.6 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 84 | 0.3 letters | Standard Deviation 0.77 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 36 | 0.3 letters | Standard Deviation 0.58 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 68 | -0.3 letters | Standard Deviation 0.79 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 40 | 0.7 letters | Standard Deviation 0.63 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 72 | 0.1 letters | Standard Deviation 0.79 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 44 | 0.6 letters | Standard Deviation 0.65 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 92 | -1.0 letters | Standard Deviation 0.78 |
| Intravitreal Arm | Change From Baseline in BCVA Score Over Time | Week 48 | -0.2 letters | Standard Deviation 0.65 |
Secondary
Change From Baseline in Center Point Thickness (CPT) at Week 36
Time frame: Baseline to Week 36
Population: Adult patients with nAMD diagnosed within 9 months and receiving at least 4 anti-VEGF intravitreal injections (with the last injection being ranibizumab), responsive to prior anti-VEGF treatment. 14 participants (7 participants in each arm) discontinued before Week 36 or the CPT value was missing (or not able to be measured on image) for the week 36 visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PDS Implant Arm | Change From Baseline in Center Point Thickness (CPT) at Week 36 | Baseline Value | 176.9 microns | Standard Deviation 3.48 |
| PDS Implant Arm | Change From Baseline in Center Point Thickness (CPT) at Week 36 | Week 36 | 5.4 microns | Standard Deviation 2.91 |
| Intravitreal Arm | Change From Baseline in Center Point Thickness (CPT) at Week 36 | Baseline Value | 177.4 microns | Standard Deviation 3.84 |
| Intravitreal Arm | Change From Baseline in Center Point Thickness (CPT) at Week 36 | Week 36 | 2.6 microns | Standard Deviation 3.56 |
Secondary
Change From Baseline in CPT Over Time
Time frame: Baseline up to Week 96
Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 8 | 0.3 microns | Standard Deviation 2.17 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 52 | 3.2 microns | Standard Deviation 3.43 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 28 | -0.4 microns | Standard Deviation 2.5 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 56 | 2.7 microns | Standard Deviation 3.36 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 16 | 6.0 microns | Standard Deviation 3.45 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 60 | 3.9 microns | Standard Deviation 3.39 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 32 | 4.5 microns | Standard Deviation 2.69 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 64 | 5.5 microns | Standard Deviation 3.54 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 4 | 0.2 microns | Standard Deviation 2.05 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 68 | 8.4 microns | Standard Deviation 3.48 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 36 | 5.4 microns | Standard Deviation 2.91 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 72 | 8.1 microns | Standard Deviation 3.35 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 20 | 6.5 microns | Standard Deviation 2.7 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 76 | 3.4 microns | Standard Deviation 3.61 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 40 | 9.0 microns | Standard Deviation 3.37 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 80 | 6.1 microns | Standard Deviation 3.56 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 12 | 5.3 microns | Standard Deviation 2.87 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 84 | 8.4 microns | Standard Deviation 3.87 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 44 | 7.3 microns | Standard Deviation 3.13 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 88 | 9.8 microns | Standard Deviation 3.88 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 24 | 6.7 microns | Standard Deviation 2.5 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 92 | 10.3 microns | Standard Deviation 3.57 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 48 | 8.9 microns | Standard Deviation 3.55 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Week 96 | 9.9 microns | Standard Deviation 3.64 |
| PDS Implant Arm | Change From Baseline in CPT Over Time | Baseline Value | 176.9 microns | Standard Deviation 3.48 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 96 | -1.3 microns | Standard Deviation 4.48 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Baseline Value | 177.4 microns | Standard Deviation 3.84 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 4 | 2.1 microns | Standard Deviation 2.51 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 8 | 3.0 microns | Standard Deviation 2.66 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 12 | 0.3 microns | Standard Deviation 3.52 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 16 | 7.3 microns | Standard Deviation 4.23 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 20 | 1.3 microns | Standard Deviation 3.31 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 24 | -0.8 microns | Standard Deviation 3.06 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 28 | 1.6 microns | Standard Deviation 3.07 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 32 | 2.3 microns | Standard Deviation 3.29 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 36 | 2.7 microns | Standard Deviation 3.56 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 40 | 5.1 microns | Standard Deviation 4.13 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 44 | 3.4 microns | Standard Deviation 3.84 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 48 | 6.4 microns | Standard Deviation 4.36 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 52 | 6.6 microns | Standard Deviation 4.2 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 56 | 3.3 microns | Standard Deviation 4.1 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 60 | 2.5 microns | Standard Deviation 4.12 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 64 | 3.6 microns | Standard Deviation 4.34 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 68 | 2.1 microns | Standard Deviation 4.27 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 72 | 0.9 microns | Standard Deviation 4.14 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 76 | 0.1 microns | Standard Deviation 4.44 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 80 | -2.7 microns | Standard Deviation 4.38 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 84 | -2.0 microns | Standard Deviation 4.76 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 88 | -0.6 microns | Standard Deviation 4.77 |
| Intravitreal Arm | Change From Baseline in CPT Over Time | Week 92 | -1.3 microns | Standard Deviation 4.39 |
Secondary
Estimated PK Parameter Value Cmax
Cmax = Maximum Serum Concentration
Time frame: Randomization to Week 96
Population: PK Population excluding patients receiving intravitreal injections of ranibizumab in the study eye post PDS implant (including supplemental treatment), patients with fellow eye ranibizumab or bevacizumab treatment, or prior bevacizumab treatment in either eye.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PDS Implant Arm | Estimated PK Parameter Value Cmax | 0.47 ng/mL | Standard Deviation 0.16 |
Secondary
Estimated PK Parameter Value Cmin
Cmin = Minimum Serum Concentration
Time frame: Randomization to Week 96
Population: PK Population excluding patients receiving intravitreal injections of ranibizumab in the study eye post PDS implant (including supplemental treatment), patients with fellow eye ranibizumab or bevacizumab treatment, or prior bevacizumab treatment in either eye.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PDS Implant Arm | Estimated PK Parameter Value Cmin | 0.31 ng/mL | Standard Deviation 0.08 |
Secondary
Estimated PK Parameter Values AUC0-6M
AUC0-6M = Area Under the Concentration-Time Curve From 0 to 6 Months
Time frame: Randomization to Week 96
Population: PK Population excluding patients receiving intravitreal injections of ranibizumab in the study eye post PDS implant (including supplemental treatment), patients with fellow eye ranibizumab or bevacizumab treatment, or prior bevacizumab treatment in either eye.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PDS Implant Arm | Estimated PK Parameter Values AUC0-6M | 59.42 day.ng/mL | Standard Deviation 21.11 |
Secondary
Estimated PK Parameter Value t1/2 After PDS Implant Insertion
Apparent terminal half-life
Time frame: Randomization to Week 96
Population: PK Population excluding patients receiving intravitreal injections of ranibizumab in the study eye post PDS implant (including supplemental treatment), patients with fellow eye ranibizumab or bevacizumab treatment, or prior bevacizumab treatment in either eye.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PDS Implant Arm | Estimated PK Parameter Value t1/2 After PDS Implant Insertion | 442.29 day | Standard Deviation 276.92 |
Secondary
Observed Serum Ranibizumab Concentrations at Specified Timepoints
Time frame: Randomization to Week 96
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PDS Implant Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Randomization | 0.125 ng/mL | Geometric Coefficient of Variation 115 |
| PDS Implant Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Week 24 prerefill-exchange | 0.397 ng/mL | Geometric Coefficient of Variation 71.1 |
| PDS Implant Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Week 28 | 0.564 ng/mL | Geometric Coefficient of Variation 40.7 |
| PDS Implant Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Week 48 prerefill-exchange | 0.289 ng/mL | Geometric Coefficient of Variation 90.6 |
| PDS Implant Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Week 52 | 0.499 ng/mL | Geometric Coefficient of Variation 41.7 |
| PDS Implant Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Week 72 prerefill-exchange | 0.257 ng/mL | Geometric Coefficient of Variation 73.7 |
| PDS Implant Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Week 76 | 0.291 ng/mL | Geometric Coefficient of Variation 247 |
| PDS Implant Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Week 96 | 0.191 ng/mL | Geometric Coefficient of Variation 154 |
| Intravitreal Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Week 96 | 0.0680 ng/mL | Geometric Coefficient of Variation 157 |
| Intravitreal Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Randomization | 0.117 ng/mL | Geometric Coefficient of Variation 78.5 |
| Intravitreal Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Week 52 | 0.0531 ng/mL | Geometric Coefficient of Variation 123 |
| Intravitreal Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Week 24 prerefill-exchange | 0.0592 ng/mL | Geometric Coefficient of Variation 180 |
| Intravitreal Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Week 76 | 0.0500 ng/mL | Geometric Coefficient of Variation 127 |
| Intravitreal Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Week 28 | 0.0581 ng/mL | Geometric Coefficient of Variation 178 |
| Intravitreal Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Week 72 prerefill-exchange | 0.0376 ng/mL | Geometric Coefficient of Variation 152 |
| Intravitreal Arm | Observed Serum Ranibizumab Concentrations at Specified Timepoints | Week 48 prerefill-exchange | 0.0594 ng/mL | Geometric Coefficient of Variation 146 |
Secondary
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
Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PDS Implant Arm | Percentage of Participants in the PDS Implant Arm Who Undergo a Supplemental Treatment That Requires Subsequent Additional Supplemental Treatments During the Study | 2 supplemental treatments | 4.1 Percentage of Participants |
| PDS Implant Arm | Percentage of Participants in the PDS Implant Arm Who Undergo a Supplemental Treatment That Requires Subsequent Additional Supplemental Treatments During the Study | 3 supplemental treatments | 0.8 Percentage of Participants |
| PDS Implant Arm | Percentage of Participants in the PDS Implant Arm Who Undergo a Supplemental Treatment That Requires Subsequent Additional Supplemental Treatments During the Study | 5 supplemental treatments | 0.4 Percentage of Participants |
Secondary
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
Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| PDS Implant Arm | 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 | Day 1 to Week 24 | Need for supplemental treatment | 4 Participants |
| PDS Implant Arm | 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 | Day 1 to Week 24 | No need for supplemental treatment | 242 Participants |
| PDS Implant Arm | 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 | Week 25 to Week 48 | Need for supplemental treatment | 13 Participants |
| PDS Implant Arm | 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 | Week 25 to Week 48 | No need for supplemental treatment | 228 Participants |
| PDS Implant Arm | 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 | Week 49 to Week 72 | Need for supplemental treatment | 12 Participants |
| PDS Implant Arm | 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 | Week 49 to Week 72 | No need for supplemental treatment | 219 Participants |
| PDS Implant Arm | 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 | Week 73 to Week 96 | Need for supplemental treatment | 12 Participants |
| PDS Implant Arm | 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 | Week 73 to Week 96 | No need for supplemental treatment | 213 Participants |
Secondary
Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline Over Time
Time frame: Baseline up to Week 96
Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PDS Implant Arm | Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline Over Time | 52.4 Percentage of Participants |
| Intravitreal Arm | Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline Over Time | 55.6 Percentage of Participants |
Secondary
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
Population: Adult patients with nAMD diagnosed within 9 months and receiving at least 4 anti-VEGF intravitreal injections (with the last injection being ranibizumab), responsive to prior anti-VEGF treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PDS Implant Arm | Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40 | 57.8 Percentage of participants |
| Intravitreal Arm | Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40 | 58.9 Percentage of participants |
Secondary
Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline Over Time
Time frame: Baseline up to Week 96
Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PDS Implant Arm | Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline Over Time | <10 letters | 88.9 Percentage of participants |
| PDS Implant Arm | Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline Over Time | < 5 letters | 75.1 Percentage of participants |
| Intravitreal Arm | Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline Over Time | <10 letters | 84.1 Percentage of participants |
| Intravitreal Arm | Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline Over Time | < 5 letters | 73.5 Percentage of participants |
Secondary
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
Population: Adult patients with nAMD diagnosed within 9 months and receiving at least 4 anti-VEGF intravitreal injections (with the last injection being ranibizumab), responsive to prior anti-VEGF treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PDS Implant Arm | Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40 | Loss of Visual Function <10 letters | 95.1 Percentage of participants |
| PDS Implant Arm | Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40 | Loss of Visual Function <5 letters | 85.0 Percentage of participants |
| Intravitreal Arm | Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40 | Loss of Visual Function <10 letters | 95.1 Percentage of participants |
| Intravitreal Arm | Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40 | Loss of Visual Function <5 letters | 88.3 Percentage of participants |
Secondary
Percentage of Participants With Adverse Events of Special Interest
Percentage of Participants with Adverse Events of Special Interest
Time frame: Randomization to Week 96
Population: Safety Population comprising all patients who receive the study treatment, with patients grouped according to treatment actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PDS Implant Arm | Percentage of Participants With Adverse Events of Special Interest | Adverse Events of Special Interest in Study Eye | 64 Participants |
| PDS Implant Arm | Percentage of Participants With Adverse Events of Special Interest | Adverse Events of Special Interest in Fellow Eye | 21 Participants |
| PDS Implant Arm | Percentage of Participants With Adverse Events of Special Interest | Non-Ocular Adverse Events of Special Interest | 0 Participants |
| Intravitreal Arm | Percentage of Participants With Adverse Events of Special Interest | Adverse Events of Special Interest in Study Eye | 18 Participants |
| Intravitreal Arm | Percentage of Participants With Adverse Events of Special Interest | Adverse Events of Special Interest in Fellow Eye | 6 Participants |
| Intravitreal Arm | Percentage of Participants With Adverse Events of Special Interest | Non-Ocular Adverse Events of Special Interest | 0 Participants |
Secondary
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
Population: Adult patients with nAMD diagnosed within 9 months and receiving at least 4 anti-VEGF intravitreal injections (with the last injection being ranibizumab), responsive to prior anti-VEGF treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PDS Implant Arm | 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 | 1.2 Percentage of participants |
| Intravitreal Arm | 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 | 1.8 Percentage of participants |
Secondary
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
Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PDS Implant Arm | Percentage of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Over Time | 2.7 Percentage of Participants |
| Intravitreal Arm | Percentage of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Over Time | 5.3 Percentage of Participants |
Secondary
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
Population: Adult patients with nAMD diagnosed within 9 months and receiving at least 4 anti-VEGF intravitreal injections (with the last injection being ranibizumab), responsive to prior anti-VEGF treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PDS Implant Arm | 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 | 80.7 Percentage of participants |
| Intravitreal Arm | 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 | 82.1 Percentage of participants |
Secondary
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
Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PDS Implant Arm | Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Over Time | 75.6 Percentage of participants |
| Intravitreal Arm | Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Over Time | 78.1 Percentage of participants |
Secondary
Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs
Time frame: Randomization to Week 96
Population: Safety Population comprising all patients who receive the study treatment, with patients grouped according to treatment actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PDS Implant Arm | Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs | Ocular Events: Study Eye | 242 Participants |
| PDS Implant Arm | Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs | Ocular Events: Fellow Eye | 124 Participants |
| PDS Implant Arm | Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs | Non-Ocular Events | 213 Participants |
| Intravitreal Arm | Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs | Ocular Events: Study Eye | 87 Participants |
| Intravitreal Arm | Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs | Ocular Events: Fellow Eye | 65 Participants |
| Intravitreal Arm | Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs | Non-Ocular Events | 121 Participants |