Diabetic Macular Edema
Conditions
Keywords
Port Delivery System
Brief summary
This study will evaluate the efficacy, safety, and Pharmacokinetics (PK) of the PDS with ranibizumab in participants with DME when treated every 24 weeks (Q24W) compared with intravitreal (IVT) ranibizumab 0.5 milligrams (mg) every 4 weeks (Q4W). The substudy will evaluate safety of re-implanting the updated PDS with ranibizumab and the refill-exchange procedures following re-implantation in participants with DME who were previously enrolled in the main study, GR40550. Up to 100 participants from the main study 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.
Will be administered as per the schedule described in individual arm.
DRUGRanibizumab refill exchange
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)
Masking description
The substudy is a non-randomized, open-label study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years at time of signing informed consent form (ICF) * Documented diagnosis of diabetes mellitus (Type 1 or Type 2) * Glycated haemoglobin (HbA1c) level of ≤10% within 2 months prior to screening or at screening Study eye * Macular thickening secondary to DME involving the center of the fovea with CST ≥325 micrometer (µm) on SD-OCT at screening * BCVA score of 78 to 25 letters (20/32 to 20/320 approximate Snellen equivalent)
Exclusion criteria
* High-risk PDR * Active intraocular inflammation (grade trace or above) * Suspected or active ocular or periocular infection of either eye * Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a patient's participation in the study * Cerebrovascular accident or myocardial infarction within 6 months prior to randomization * Atrial fibrillation diagnosis or worsening within 6 months prior to randomization * Uncontrolled blood pressure Substudy: Inclusion Criteria: * Having experienced a septum dislodgement in the original implant while in the main study or after exiting the main study * Sufficiently clear ocular media and adequate pupillary dilation to allow for analysis and grading by central reading center
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in BCVA Score From Baseline Averaged Over Weeks 60 and 64 as Measured Using the ETDRS Chart in the Efficacy Population Using a Treatment Policy Strategy for all Intercurrent Events | Baseline to Week 64 | BCVA = Best-Corrected Visual Acuity 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. |
| Substudy: Number of Participants With Ocular and Systemic (Non-ocular) Adverse Events (AEs) and Severity of Ocular and Systemic AEs | Baseline to Week 72 | — |
| Substudy: Number of Participants With Adverse Events of Special Interests (AESIs) and Severity of AESIs | Baseline to Week 72 | — |
| Substudy: Duration of AESIs | Baseline to Week 72 | — |
| Substudy: Number of Participants With Ocular AESIs and Severity of Ocular AESIs During the Post-operative Period | Up to Day 37 post re-implantation | — |
| Substudy: Number of Participants With Ocular AESIs and Severity of Ocular AESIs During the Follow-up Period | > 37 days post-implantation (up to approximately 72 weeks) | — |
| Substudy: Duration of Ocular AESIs During the Post-operative Period | Up to Day 37 post re-implantation | — |
| Substudy: Duration of Ocular AESIs During the Follow-up Period | > 37 days post-implantation (up to approximately 72 weeks) | — |
| Substudy: Number of Participants With Adverse Device Effects (ADEs) and Severity of ADEs | Baseline to Week 72 | — |
| Substudy: Number of Participants With Anticipated Serious ADEs | Baseline to Week 72 | — |
| Substudy: Duration of Serious ADEs | Baseline to Week 72 | — |
| Substudy: Number of Device Deficiencies | Baseline to Week 72 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in BCVA Score From Baseline Averaged Over Weeks 60 and 64 as Measured With Use of the ETDRS Chart in the Modified Intent-to-treat (mITT) Population Using a Treatment Policy Strategy for All Intercurrent Events | Baseline to Week 64 | ETDRS-DRSS = ETDRS Diabetic Retinopathy Severity Scale |
| Change in BCVA Score From Baseline Averaged Over Weeks 60 and 64 as Measured With Use of the ETDRS Chart in the mITT Population Using a Hypothetical Strategy for All Intercurrent Events | Baseline to Week 64 | — |
| Percentage of Participants With a ≥2-step Improvement From Baseline on the ETDRS-DRSS at Week 64 in the Efficacy Population | Baseline to Week 64 | — |
| Percentage of Participants With a ≥2-step Improvement From Baseline on the ETDRS-DRSS at Week 64 in the mITT population | Baseline to Week 64 | — |
| Change from Baseline in BCVA as Measured on the ETDRS Chart Over Time | Baseline up to Week 120 | — |
| Percentage of Participants Who Lose <15, <10, and <5 letters in BCVA From Baseline Over Time | Baseline up to Week 120 | — |
| Percentage of Participants Who Gain ≥15, ≥10, ≥5, ≥0 Letters in BCVA From Baseline Over Time | Baseline up to Week 120 | — |
| Percentage of Participants With a BCVA Snellen Equivalent of 20/40 or Better Over Time | Baseline up to Week 120 | — |
| Percentage of Participants With a BCVA Snellen Equivalent of 20/200 or Worse Over Time | Baseline up to Week 120 | — |
| Percentage of Participants With a ≥2-step Improvement From Baseline on the ETDRS-DRSS Over Time | Baseline up to Week 120 | — |
| Percentage of Participants With a ≥3-step Improvement From Baseline on the ETDRS-DRSS Over Time | Baseline up to Week 120 | — |
| Time to ≥2-step Worsening From Baseline on the ETDRS-DRSS | Baseline up to Week 120 | — |
| Time to ≥3-step Worsening From Baseline on the ETDRS-DRSS | Baseline up to Week 120 | — |
| Change From Baseline in ETDRS-DRSS Score Over Time | Baseline up to Week 120 | — |
| Change From Baseline in Central Subfield Thickness (CST) as Measured on Spectral Domain Optical Coherence Tomography (SD-OCT) Over Time | Baseline up to Week 120 | — |
| Change From Baseline in Total Macular Volume as Measured on SD-OCT Over Time | Baseline up to Week 120 | — |
| Percentage of Participants With Absence of Intraretinal Fluid (IRF) Over Time (IRF as Measured in the Central 1 mm Subfield) | Baseline up to Week 120 | — |
| Percentage of Participants With Absence of Subretinal Fluid (SRF) Over Time (SRF as Measured in the Central 1 mm Subfield) | Baseline up to Week 120 | — |
| Percentage of Participants With Absence of IRF and SRF Over Time | Baseline up to Week 120 | — |
| Percentage of Participants With Absence DME (Defined as CST ≥325 μm on SD-OCT) Over Time | Baseline up to Week 120 | DME = diabetic macular edema |
| Time to PDR (Defined as a Score ≥60 on the ETDRS-DRSS) | Baseline up to Week 120 | PDR = proliferative diabetic retinopathy |
| Percentage of Participants Who do not Undergo Supplemental Treatment With IVT Ranibizumab Within Each Refill-exchange Interval | Baseline up to Week 120 | — |
| Percentage of Participants Who Report Preferring PDS Treatment Compared With IVT Ranibizumab Treatment | Baseline to Week 64 | As measured by the PDS patient preference questionnaire (PPPQ) at Week 64 among participants in the PDS arm efficacy population, mITT population |
| Percentage of Participants Who Report Preferring PDS Treatment Compared With IVT Ranibizumab Treatment, as Measured by the PPPQ at Week 64 | Baseline to Week 64 | Participants in a subset of patients with bilateral disease who are simultaneously receiving ranibizumab via study eye PDS implant and fellow eye IVT injection. |
| Participant-reported Vision-related Functioning and Health-Related Quality of Life (HRQoL) Among Participants in Both Treatment Arms, as Measured by Changes From Baseline | , Baseline Week 48, Week 96 | As measured by in the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) composite score and Near Activities, Distance Activities, and Driving subscale scores |
| Participant-reported Vision-related Functioning and HRQoL, as Measured by the Proportion of Participants With a ≥ 4-Point Improvement From Baseline in the NEI VFQ-25 Composite Score at Weeks 48 and 96 Among Participants in Both Treatment Arms | Baseline, Week 48, Week 96 | — |
| Incidence and Severity of Ocular AEs | Baseline to Week 120 | — |
| Incidence and Severity of Non-ocular AEs | Baseline up to Week 120 | — |
| Incidence, Severity, and Duration of AEs of Special Interest | Baseline up to Week 120 | — |
| Serum Concentration of Ranibizumab Observed Over Time | Baseline up to Week 120 | — |
| PK Parameter: Value Area Under the Concentration- Time Curve Over 24 weeks (AUC24W) | Baseline to Week 24 | — |
| PK Parameter: Maximum Serum Concentration (Cmax) | Baseline up to Week 120 | — |
| PK Parameter: Minimum Serum Concentration (Cmin) | Baseline up to Week 120 | — |
| Time of Maximum Observed Serum Concentration (Tmax) After PDS Implant Insertion | Baseline up to Week 120 | — |
| Prevalence of Anti-drug Antibodies (ADAs) at Baseline and Incidence of ADAs During the Study | Baseline up to Week 120 | — |
| Prevalence of Neutralizing Antibodies at Baseline and Incidence of Neutralizing Antibodies During the Study | Baseline up to Week 120 | — |
| Reported Incidence of Device Deficiencies | Baseline up to Week 120 | — |
| Incidence, Severity, and Duration of AESIs | Baseline up to Week 120 | — |
| Incidence, Severity, and Duration of Ocular AESIs During the Postoperative Period (up to 37 Days After Initial Implantation) and Follow-up Period (> 37 days After Implantation Surgery) | Baseline up to Week 120 | — |
| Incidence and Severity of ADEs | Baseline up to Week 120 | — |
| Incidence, Causality, Severity, and Duration of Anticipated Serious ADEs | Baseline up to Week 120 | — |
| Substudy: Number of Participants With Ocular AESIs and Severity of Ocular AESIs After Refill-exchange Procedure | Up to approximately 72 weeks | — |
| Substudy: Duration of AESIs After Refill-exchange Procedure | Up to approximately 72 weeks | — |
| Substudy: Number of Participants With ADEs and Severity of ADEs After Refill-exchange Procedure | Up to approximately 72 weeks | — |
| Substudy: Number of Participants With Anticipated Serious ADEs After Refill-exchange Procedure | Up to approximately 72 weeks | — |
| Substudy: Duration of Serious ADEs After Refill-exchange Procedure | Up to approximately 72 weeks | — |
| Substudy: Number of Device Deficiencies After Refill-exchange Procedure | Up to approximately 72 weeks | — |
Countries
United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed