Neovascular Age-Related Macular Degeneration
Conditions
Brief summary
This study will evaluate the long-term safety and tolerability of the Port Delivery System with ranibizumab (PDS) (100 mg/mL) in participants with neovascular age-related macular degeneration (nAMD) who have either completed Phase II Study GX28228 (Ladder), Phase III Study GR40548 (Archway), Phase IIIb Study WR42221 (Velodrome), or completed Week 24 visit in Study WR42221 but were not eligible to be randomized in WR42221.
Detailed description
The Transscleral Photocoagulation sub-study (sub-study 1) will evaluate the effectiveness of using transscleral photocoagulation (TPC) with the Iridex laser system to mitigate vitreous hemorrhages secondary to the Port Delivery System with ranibizumab (PDS) implantation procedure in participants with neovascular age-related macular degeneration (nAMD). The sub-study will enroll about 55 participants. The Re-implantation sub-study (sub-study 2) will evaluate the safety of re-implantation with the updated PDS with ranibizumab . Up to 100 participants who previously participated in the main study in the United States will be enrolled and followed for a maximum of 72 weeks post-re-implantation in the substudy.
Interventions
Will be administered as per the schedule described in individual arm
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The sub-study 1 and sub-study 2 are open-label studies.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Previous enrollment in and completion of Study GX28228 (Ladder) or Study GR40548 (Archway), without early treatment or study discontinuation in either study OR Previous enrollment in Study WR42221 (Velodrome) and either not eligible to be randomized in Study WR42221 at Week 24 or completed the study (from the Q24W or Q36W arm) * Ability and willingness to undertake all scheduled visits and assessments * For women of childbearing potential: agreement to remain abstinent or use contraceptive measures
Exclusion criteria
* Pregnant or breastfeeding, or intending to become pregnant during the treatment period and for at least 28 days after the last intravitreal injection of ranibizumab or 1 year after the last Implant refill-exchange of ranibizumab * History of other ocular diseases that give reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab, that might affect interpretation of the results of the study or that renders the participant at high risk for treatment complications * History of other diseases, 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 that renders the participant at high risk of treatment complications * Requirement for continuous use of any medications or treatments indicated in the "Prohibited Therapy" Sub-study 1 Inclusion Criteria \- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures Participants must meet the following ocular criteria for the study eye for substudy entry: * Diagnosis of exudative nAMD within 2 years prior to the enrollment visit * Previous treatment with at least two anti-VEGF ITV injections (e.g., ranibizumab, bevacizumab, or aflibercept) for nAMD per standard of care within 6 months prior to the enrollment visit * Demonstrated response to prior anti-VEGF ITV treatment since diagnosis, as evidenced at enrollment by the following: Overall decrease in nAMD disease activity detected on SD-OCT AND Stable or improved best-corrected visual acuity (BCVA) * All subtypes of nAMD lesions are permissible (i.e., type I, type II, type III, or mixed forms per optical coherence tomography (OCT) classification) nAMD lesions at the time of diagnosis must involve the macula (6 mm diameter centered at the fovea). * Sufficiently clear ocular media and adequate pupillary dilation to allow for analysis and grading by the central reading center of FP and SD-OCT images.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Sub-study 2: Number of participants with Ocular AESIs and Severity of Ocular AESIs During the Follow-up Period | > 37 days post re-implantation (up to approximately Week 72) |
| Sub-study 2: Duration of Ocular AESIs During the Post-operative Period | Up to Day 37 post re-implantation |
| Sub-study 2: Duration of Ocular AESIs During the Follow-up Period | > 37 days post re-implantation (up to approximately Week 72) |
| Sub-study 2: Number of Participants with Adverse Device Effects (ADEs) and Severity of ADEs | Baseline to Week 72 |
| Sub-study 2: Number of Participants with Anticipated Serious ADEs and Severity of Anticipated Serious ADEs | Baseline to Week 72 |
| Sub-study 2: Duration of Anticipated Serious ADEs | Baseline to Week 72 |
| Sub-study 2: Number of Device Deficiencies | Baseline to Week 72 |
| Sub-study 2: Number of Participants with Ocular and Systemic (Non-ocular) Adverse Events (AEs) and Severity of These AEs | Baseline to Week 72 |
| Sub-study 2: Number of Participants with Adverse Events of Special Interests (AESIs) and Severity of AESIs | Baseline to Week 72 |
| Sub-study 2: Duration of AESIs | Baseline to Week 72 |
| Sub-study 2: Number of participants with Ocular AESIs and Severity of Ocular AESIs During the Post-operative Period | Up to Day 37 post re-implantation |
| Incidence, Severity, and Duration of PDS-Associated Ocular AESIs During the Postoperative Period (Up to 37 days of Initial Implantation) and Follow-Up Period (>37 days After Implantation Surgery) for Participants who Receive the PDS Implant in the Study | Baseline up to Week 240 |
| Incidence and Severity of Adverse Device Effects | Baseline up to Week 240 |
| Incidence, Causality, Severity, And Duration Of Anticipated Serious Adverse Device Effects | Baseline up to Week 240 |
| Sub-study 1: Rate of Vitreous Hemorrhage Secondary to Choroidal Bleeding That Does not Resolve by the Week 4 Visit After Implant Insertion Surgery. | Baseline to Week 4 |
| Incidence and Severity of Ocular and Systemic (Non-Ocular) Adverse Events (AEs) | Baseline up to Week 240 |
| Incidence, Severity, and Duration of Adverse Event of Special Interest (AESIs) | Baseline up to Week 240 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sub-study 1: Distribution of Vitreous Hemorrhage Grade in the Study eye Over Time | Baseline up to Week 104 | — |
| Sub-study 1: Rate of Vitrectomy in the Study eye | Baseline up to Week 104 | — |
| Sub-study 1: Percentage of Participants who Lose <15, <10, or <5 Letters in BCVA Score From Baseline Over Time | Baseline up to Week 104 | — |
| Sub-study 1: Change in BCVA Score From Baseline Over Time | Baseline up to Week 104 | — |
| Sub-study 1: Change from Baseline in CPT Over Time | Baseline up to Week 104 | — |
| Sub-study 1: Change From Baseline in Center Subfield Thickness (CST) Over Time | Baseline up to Week 104 | — |
| Sub-study 2: Number of Participants with Ocular AESIs and Severity of AESIs Following Refill-exchange | Up to approximately Week 72 | — |
| Sub-study 2: Duration of AESIs Following Refill-exchange | Up to approximately Week 72 | — |
| Sub-study 2: Number of Participants With ADEs and Severity of ADEs Following Refill-exchange | Up to approximately Week 72 | — |
| Sub-study 2: Number of Participants with Anticipated Serious ADEs and Severity of Anticipated Serious ADEs Following Refill-exchange | Up to approximately Week 72 | — |
| Sub-study 2: Number of Device Deficiencies Following Refill-exchange | Up to approximately Week 72 | — |
| Change in Best-Corrected Visual Acuity (BCVA) Score from Baseline Over Time, as Assessed using the ETDRS Visual Acuity Chart at a Starting Distance of 4 Meters | Baseline up to Week 240 | ETDRS = Early Treatment Diabetic Retinopathy Study A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind. |
| Percentage of Participants who Lose <15, <10, or <5 Letters in BCVA Score from Baseline Over Time | Baseline up to Week 240 | — |
| Percentage of Participants with BCVA Score of 38 Letters (of 20/200 Approximate Snellen Equivalent) or Worse over Time | Baseline up to Week 240 | — |
| Percentage of Participants with BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better over Time | Baseline up to Week 240 | — |
| Change from Baseline in Center Point Thickness (CPT) Over Time | Baseline up to Week 240 | CPT is defined as the 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 is measured using optical coherence tomography (OCT). |
| Percentage of Participants who Undergo Supplemental Treatment with Intravitreal Ranibizumab 0.5 mg During Each Refill-exchange Interval | Baseline up to Week 240 | — |
| Sub-study 1: Incidence of Ocular Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) in the Study eye | Baseline up to Week 104 | — |
| Sub-study 1: Incidence of AEs Commonly Seen After Transscleral Cyclophotocoagulation (TS-CPC) for Treatment of Glaucoma in the Study eye | Baseline up to Week 104 | — |
| Sub-study 1: Time From Surgery to Vitreous Hemorrhage Resolution in the Study eye | Baseline up to Week 104 | — |
| Sub-study 1: Incidence of Vitreous Hemorrhage Grade 3 and Higher in the Study eye over time | Baseline up to Week 104 | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, France, Germany, Israel, Italy, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTReference Study ID Number: GR40549 https://forpatients.roche.com/ No attachments to email below.
CONTACTFastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed