A Study to Evaluate Efficacy, Safety & Pharmacokinetics of the Port Delivery System (PDS) With Ranibizumab in Participants With Diabetic Macular Edema (DME) Compared With Intravitreal Ranibizumab; A Subtudy to Evaluate the Safety of Re-Implanting the PDS With Ranibizumab in Participants With DME
Phase 3
Recruiting
- Conditions
- Diabetic Macular Edema
- Interventions
- Drug: PDS Implant Pre-Filled with 100 mg/mL RanibizumabDrug: Intravitreal Ranibizumab 0.5 mg Injection
- Registration Number
- NCT04108156
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will evaluate the efficacy, safety, and pharmacokinetics of the PDS with Ranibizumab in participants with DME when treated every 24 weeks (Q24W) compared with intravitreal ranibizumab 0.5 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 634
Inclusion Criteria
- Age ≥18 years at time of signing Informed Consent Form
- Documented diagnosis of diabetes mellitus (Type 1 or Type 2)
- 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 um on SD-OCT at screening
- BCVA score of 78 to 25 letters (20/32 to 20/320 approximate Snellen equivalent)
Exclusion Criteria
- High-risk proliferative diabetic retinopathy
- 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
Exclusion Criteria (Cohort 1 Only):
- Recent history (in the last 3 months prior to enrollment) of other disease, other non-diabetic metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of ranibizumab or surgical placement of the PDS implant; that might affect interpretation of the results of the study; or that renders the participant at high risk for treatment complications
- Active cancer within the last 12 months, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or prostate cancer
- Current systemic treatment for a confirmed active systemic infection
- Participation in an investigational trial that involves treatment with any drug or device (with the exception of vitamins and minerals or enrollment in Study GR40550) within 6 months prior to enrollment
- Use of antimitotic or antimetabolite therapy within 30 days
Ocular Exclusion Criteria for Study Eye:
- Any ocular condition that may render the participant at high risk for surgical or treatment complications
- Intraocular surgery (including cataract surgery) within 1 month preceding the enrollment visit
- Any use of medicated intraocular implants (other than the PDS implant), at any time prior to enrollment
- History of rhegmatogenous retinal tears or peripheral retinal breaks within 3 months prior to the enrollment visit
- Any concurrent ocular condition that would require surgical intervention during the study to prevent or treat visual loss
- Concurrent conjunctival, Tenon's capsule, and/or scleral condition in the supero-temporal quadrant of the eye (e.g., scarring, thinning, mass) that may affect the refill-exchange procedure of the PDS implant
- Ongoing ocular complications that might affect participant safety Ocular Exclusion Criteria for Either Eye
- Suspected or active ocular or periocular infection (e.g., infectious conjunctivitis or endophthalmitis)
- Any history of uveitis
- Active blepharitis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PDS Arm Ranibizumab refill exchange Participants randomized to the PDS arm will receive intravitreal ranibizumab injection every 4 weeks (loading phase) and will then have the PDS implant (pre-filled with ranibizumab) surgically inserted. PDS implant refill-exchange procedures will be performed on a fixed interval every 24-weeks (Q24W) thereafter Intravitreal Arm Ranibizumab refill exchange Participants randomized to the intravitreal arm will receive intravitreal ranibizumab injection every 4 weeks until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q24W thereafter. Substudy: Cohort 1 Ranibizumab refill exchange Participants will undergo re-implantation with the updated PDS implant (pre-filled with ranibizumab 100 mg/mL) on Day 1 (or enrollment visit) and then will have two refill-exchanges (ranibizumab 100 mg/mL) Q24W up to 48 weeks. Substudy: Cohort 2a Ranibizumab refill exchange Participants who received an updated PDS implant, have \< 24 weeks post-re-implantation follow-up and no refill exchange visit in the main study, will undergo two refill-exchange procedures (ranibizumab 100 mg/mL) Q24W, post main study re-implantation visit. Substudy: Cohort 2b Ranibizumab refill exchange Participants who received an updated PDS implant, have \< 48 weeks post-re-implantation follow-up and one refill exchange visit in the main study, will undergo one refill-exchange procedure (ranibizumab 100 mg/mL) Q24W, post main study re-implantation visit. Substudy: Cohort 1 PDS Implant Pre-Filled with 100 mg/mL Ranibizumab Participants will undergo re-implantation with the updated PDS implant (pre-filled with ranibizumab 100 mg/mL) on Day 1 (or enrollment visit) and then will have two refill-exchanges (ranibizumab 100 mg/mL) Q24W up to 48 weeks. PDS Arm PDS Implant Pre-Filled with 100 mg/mL Ranibizumab Participants randomized to the PDS arm will receive intravitreal ranibizumab injection every 4 weeks (loading phase) and will then have the PDS implant (pre-filled with ranibizumab) surgically inserted. PDS implant refill-exchange procedures will be performed on a fixed interval every 24-weeks (Q24W) thereafter Intravitreal Arm Intravitreal Ranibizumab 0.5 mg Injection Participants randomized to the intravitreal arm will receive intravitreal ranibizumab injection every 4 weeks until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q24W thereafter.
- Primary Outcome Measures
Name Time Method 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: 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 Substudy: Duration of AESIs Baseline to Week 72
- Secondary Outcome Measures
Name Time Method 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 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
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 CST as Measured on 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 Over Time (Intraretinal Fluid as Measured in the Central 1 mm Subfield) Baseline up to Week 120 Percentage of Participants with Absence of Subretinal Fluid Over Time (Subretinal Fluid as Measured in the Central 1 mm Subfield) Baseline up to Week 120 Percentage of Participants with Absence of Intraretinal Fluid and Subretinal Fluid 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 Intravitreal Ranibizumab Within Each Refill-Exchange Interval Baseline up to Week 120 Percentage of Participants Who Report Preferring PDS Treatment Compared with Intravitreal Ranibizumab Treatment Baseline to Week 64 As measured by the PDS Patient Preference Questionnaire at Week 64 among patients in the PDS arm efficacy population, mITT population
Percentage of Participants Who Report Preferring PDS Treatment Compared with Intravitreal Ranibizumab Treatment, as Measured by the PDS Patient Preference Questionnaire (PPPQ) at Week 64 Baseline to Week 64 Participants in in a subset of patients with bilateral disease who are simultaneously receiving ranibizumab via study eye PDS implant and fellow eye intravitreal injection
Patient-reported Vision-Related Functioning and Health-Related Quality of Life (HRQoL) Among Patients 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
Patient-reported Vision-related Functioning and HRQoL, as Measured by the Proportion of Patients with a ≥ 4-Point Improvement from Baseline in the NEI VFQ-25 Composite Score at Weeks 48 and 96 Among Patients in Both Treatment Arms Baseline, Week 48, Week 96 Incidence and Severity of Ocular Adverse Events Baseline up to Week 120 Incidence and Severity of Non-ocular Adverse Events Baseline up to Week 120 Incidence, Severity, and Duration of Adverse Events 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 Pharmacokinetic (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 Ocular Adverse Events of Special Interest 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 Adverse Device Effects 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
Trial Locations
- Locations (90)
Barnet Dulaney Perkins Eye Center
🇺🇸Mesa, Arizona, United States
Retinal Consultants of Arizona;Opthalmology
🇺🇸Phoenix, Arizona, United States
Arizona Retina and Vitreous Consultants
🇺🇸Phoenix, Arizona, United States
Associated Retina Consultants
🇺🇸Phoenix, Arizona, United States
California Retina Consultants
🇺🇸Bakersfield, California, United States
Retina-Vitreous Associates Medical Group
🇺🇸Beverly Hills, California, United States
The Retina Partners
🇺🇸Encino, California, United States
Retina Consultants of Orange County;Clinical Research
🇺🇸Fullerton, California, United States
Jules Stein Eye Institute/ UCLA
🇺🇸Los Angeles, California, United States
Northern California Retina-Vitreous Associates
🇺🇸Mountain View, California, United States
Scroll for more (80 remaining)Barnet Dulaney Perkins Eye Center🇺🇸Mesa, Arizona, United States