nAMD, Neovascular Age-related Macular Degeneration
Conditions
Brief summary
This study will evaluate the efficacy, safety, and PK of ranibizumab 100 milligrams per milliliter (mg/mL) delivered every 24 weeks (Q24W) via the PDS implant compared with ranibizumab 0.5 milligrams (mg) delivered every 4 weeks (Q4W) as intravitreal (IVT) injection in Chinese participants with nAMD.
Interventions
DEVICEPDS With Ranibizumab (100 mg/mL)
Participants randomized to the implant arm will have the implant (filled prior to implantation with approximately 20 microliters (μL) of the 100 mg/mL formulation of ranibizumab \[approximately 2 mg dose of ranibizumab\]) surgically inserted in the study eye at the Day 1 visit following their randomization visit, or at Week 48 visit for participants randomized to the IVT arm. After the initial fill of the implant with ranibizumab, participants will receive implant refill-exchanges at fixed 24-week intervals.
DRUGRanibizumab (10 mg/mL)
Participants in the IVT arm will receive their first IVT injection of 50 μL of the 10 mg/mL ranibizumab (0.5 mg dose) at the Day 1 visit, which will occur at the conclusion of the randomization visit. Afterwards, participants will receive IVT ranibizumab injections of 50 μL of the 10 mg/mL formulation Q4W at each scheduled study visit until Week 44 and bi-monthly visits thereafter, followed by visits every two months until study completion.
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
* Initial diagnosis of nAMD within 9 months prior to the screening visit * Previous treatment with at least three anti-vascular endothelial growth factor (VEGF) IVT injections for nAMD per standard-of-care (SOC) within 6 months prior to the screening visit * Demonstrated response to prior anti-VEGF IVT treatment since diagnosis * Availability of historical VA data prior to the first anti-VEGF treatment for nAMD up to the screening visit * BCVA of 34 letters or better (20/200 or better approximate Snellen equivalent), using Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters * All subtypes of nAMD lesions are permissible * Sufficiently clear ocular media and adequate pupillary dilation to allow for analysis and grading by the central reading center of fundus photography (FP), fluorescein angiography (FA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF), and optical coherence tomography (OCT) images
Exclusion criteria
A. Prior Ocular Treatment Study Eye * History of vitrectomy surgery, submacular surgery, or other surgical intervention, all for AMD * Prior treatment with Visudyne, external-beam radiation therapy, or transpupillary thermotherapy * Previous treatment with corticosteroid IVT injection or corticosteroid implants * Previous intraocular device implantation (not including intraocular lens implants) * Previous laser (any type) used for age-related macular degeneration (AMD) treatment * Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit * Prior treatment with IVT treatments for geographic atrophy * Concurrent conjunctival, Tenon's capsule, and/or scleral condition in the supero-temporal quadrant of the eye that may affect the implantation, subsequent tissue coverage, and refill-exchange procedure of the PDS implant Either Eye * Prior treatment with brolucizumab * Prior gene therapy for nAMD or other ocular diseases * Previous participation in any ocular disease studies of investigational drugs and/or devices, within 3 months or five elimination half-lives of the investigational therapy, whichever is longer, preceding the screening visit B. Choroidal Neovascularization (CNV) Lesion Characteristics Study Eye * Subretinal hemorrhage that involves the center of the fovea, if the hemorrhage is greater than 0.5 disc area (1.27 millimeter square \[mm\^2\]) in size at screening * Subfoveal fibrosis or subfoveal atrophy Either Eye • CNV due to other causes, such as ocular histoplasmosis, trauma, central serous chorio-retinopathy, or pathologic myopia C. Concurrent Ocular Conditions Study Eye * Retinal pigment epithelial tear * Any concurrent intraocular condition * Active intraocular inflammation (grade trace or above) * History of vitreous hemorrhage * History of rhegmatogenous retinal detachment * History of rhegmatogenous retinal tears or peripheral retinal breaks within 3 months prior to the randomization visit * History of pars plana vitrectomy surgery * Aphakia or absence of the posterior capsule * Spherical equivalent of the refractive error demonstrating more than 8 diopters of myopia * Preoperative refractive error that exceeds 8 diopters of myopia, for participants who have undergone prior refractive or cataract surgery * Intraocular surgery (including cataract surgery) within 3 months preceding the randomization visit * Uncontrolled ocular hypertension or glaucoma * History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery * History of corneal transplant Fellow (Non-Study) Eye • Non-functioning fellow eye Either Eye * Any history of uveitis * Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Best-corrected Visual Acuity (BCVA) Score Averaged Over Weeks 36 and 40, as Assessed Using the ETDRS Visual Acuity (VA) Chart at a Starting Distance of 4 Meters | Baseline up to Week 40 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Center Point Thickness (CPT) at Week 36 | Baseline and Week 36 | CPT is retinal thickness in the center point of the fovea measured between the internal limiting membrane and the inner third of the retinal pigment epithelium layer. CPT will be measured using optical coherence tomography (OCT). |
| Change From Baseline in Central Subfield Thickness (CST) at Week 36 | Baseline and Week 36 | CST is defined as the average thickness of the central 1 millimeter (mm) circle of the ETDRS grid centered on the fovea. CST will be measured using OCT. |
| Change From Baseline in CPT at Week 44 | Baseline and Week 44 | CPT is retinal thickness in the center point of the fovea measured between the internal limiting membrane and the inner third of the retinal pigment epithelium layer. CPT will be measured using OCT. |
| Change From Baseline in CST at Week 44 | Baseline and Week 44 | CST is defined as the average thickness of the central 1 mm circle of the ETDRS grid centered on the fovea. CST will be measured using OCT. |
| Proportion of Participants in the Implant Arm Who do not Undergo Supplemental Treatment With IVT Ranibizumab 0.5 mg Before the First, Second, Third, Fourth, Fifth, and Sixth Fixed Refill-exchange Intervals | Baseline up to 144 weeks | — |
| Proportion of Participants in the Implant Arm Who do not Undergo a Supplemental Treatment that Requires Subsequent Additional Supplemental Treatments During the Study | Baseline up to 144 weeks | — |
| Percentage of Participants With Adverse Events (AEs) | Baseline up to 144 weeks | — |
| Percentage of Participants With Adverse Events of Special Interest (AESIs) | Baseline up to 144 weeks | — |
| Duration of AESIs | Baseline up to 144 weeks | — |
| Percentage of Participants With Ocular AESIs During the Post-operative Period and Follow-up Period | Post-operative period: up to 37 days after initial implantation Follow-up period: > 37 days after implantation surgery (up to 144 weeks) | — |
| Percentage of Participants Who Received PDS Affected With Adverse Device Effects (ADEs) | Baseline up to 144 weeks | — |
| Percentage of Participants Who Received PDS Affected With Anticipated Serious Adverse Device Effects (ASADEs) | Baseline up to 144 weeks | — |
| Duration of ASADEs | Baseline up to 144 weeks | — |
| Number of Device Deficiencies | Baseline up to 144 weeks | — |
| Observed Serum Ranibizumab Concentrations at Specified Timepoints | Implant Arm: Weeks 4, 12, 24, 28, 36, 48, 96, 144 and early study termination (EST) visit; IVT Arm: Weeks 4, 24, 36, 48, 52, 60, 72, 76, 84, 96, 144 & EST visit (up to 156 weeks) | — |
| Area Under the Concentration Time Curve (AUC) From 0-24 Weeks | Baseline, Weeks 4, 12, and 24 | — |
| Maximum Serum Concentration (Cmax) of Ranibizumab | Implant Arm: Weeks 4, 12, 24, 28, 36, 48, 96, 144 & EST visit; IVT Arm: Weeks 52, 60, 72, 76, 84, 96, 144, & EST visit (up to 156 weeks) | — |
| Minimum Serum Concentration (Cmin) of Ranibizumab | Implant Arm: Weeks 4, 12, 24, 28, 36, 48, 96, 144, & EST visit; IVT Arm: Weeks 52, 60, 72, 76, 84, 96, 144, & EST visit (up to 156 weeks) | — |
| Number of Participants With Anti-drug Antibodies (ADAs) to Ranibizumab | Implant Arm: Baseline; Weeks 4, 24, 36, 48, 96, 144 & EST visit; IVT Arm: Baseline, Weeks 4, 24, 36, 48, 52, 72, 96, 144 & EST visit (up to 156 weeks) | — |
| Number of Participants With Treatment-emergent ADAs to Ranibizumab During the Study | Implant Arm: Weeks 4, 24, 36, 48, 96, 144, & EST visit; IVT Arm: Weeks 4, 24, 36, 48, 52, 72, 96, 144, & EST visit (up to 156 weeks) | — |
| Proportion of Participants Who Lose < 10 or < 5 Letters in BCVA Score From Baseline Averaged Over Weeks 36 and 40 | Baseline up to Week 40 | — |
| Change From Baseline in BCVA Score Over Time | Baseline up to Week 144 | — |
| Proportion of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Averaged Over Weeks 36 and 40 | Baseline up to Week 40 | — |
| Proportion of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Averaged Over Weeks 44 and 48 | Baseline up to Week 48 | — |
| Proportion of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Averaged over Weeks 36 and 40 | Baseline up to Week 40 | — |
| Proportion of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Averaged Over Weeks 44 and 48 | Baseline up to Week 48 | — |
| Proportion of Participants Who Gain ≥ 0 Letters in BCVA Score From Baseline Averaged Over Weeks 36 and 40 | Baseline up to Week 40 | — |
| Proportion of Participants Who Lose < 10 or < 5 Letters in BCVA Score From Baseline Averaged Over Weeks 44 and 48 | Baseline up to Week 48 | — |
| Proportion of Participants Who Gain ≥ 0 Letters in BCVA Score From Baseline Averaged Over Weeks 44 and 48 | Baseline up to Week 48 | — |
Countries
China
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed