A Multicenter, Randomized Study in Participants With Diabetic Retinopathy Without Center-involved Diabetic Macular Edema To Evaluate the Efficacy, Safety, and Pharmacokinetics of Ranibizumab Delivered Via the Port Delivery System Relative to the Comparator Arm
- Conditions
- Diabetic Retinopathy
- Interventions
- Drug: PDS Implant Pre-Filled with 100 mg/mL RanibizumabDrug: Intravitreal Ranibizumab 0.5 mg Injection
- Registration Number
- NCT04503551
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
Study GR41675 is a Multicenter, Randomized Study in Participants with Diabetic Retinopathy (DR) Without Center-Involved Diabetic Macular Edema (CI-DME) to Evaluate the Efficacy, Safety of the Port Delivery System with Ranibizumab (PDS) Relative to the Comparator Arm
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 174
- Age ≥18 years at time of signing Informed Consent Form
- Documented diagnosis of diabetes mellitus (Type 1 or Type 2)
- HbA1c level of ≤12% within 2 months prior to screening or at screening
Inclusion Criteria for Study Eye
- Moderately severe or severe NPDR (ETDRS-DRSS level 47 or 53)
- BCVA score of ≥ 69 letters (20/40 approximate Snellen equivalent or better)
- Uncontrolled blood pressure
- Cerebrovascular accident or myocardial infarction within 6 months prior to randomization
- Atrial fibrillation diagnosis or worsening within 6 months prior to randomization
- Current systemic treatment for a confirmed active systemic infection
- Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis, or anticipated to require hemodialysis or peritoneal dialysis at any time during the study
- History 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 patient at high risk for treatment complications in the opinion of the investigator or Sponsor
Ocular Exclusion Criteria for Study Eye:
- Presence of center-involved diabetic macular edema (defined as CST ≥325 µm)
- Any intravitreal anti-VEGF treatment at any time prior to randomization
- Any use of medicated intraocular implants, including Ozurdex® or Iluvien® implants at any time prior to randomization
- Any intravitreal corticosteroid treatment at any time prior to randomization
- Any periocular (e.g., subtenon) corticosteroid treatment at any time prior to randomization
- Any PRP at any time prior to randomization
- Any macular laser photocoagulation (such as micropulse and focal or grid laser) at any time prior to randomization
- Active intraocular inflammation (grade trace or above)
- Clinically significant abnormalities of the vitreous-retinal interface involving the macular area or disrupting the macular architecture, such as vitreous-retinal traction or epiretinal membrane (assessed by the investigator and confirmed by the central reading center)
- Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a participant's participation in the study
- History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
- Any concurrent ocular condition (e.g., cataract, epiretinal membrane) that would require surgical intervention during the study to prevent or treat visual loss that might result from that condition
- Any concurrent ocular condition (e.g., amblyopia, strabismus) that may affect interpretation of study results
- History of other ocular diseases that gives reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab, that might affect interpretation of study results, or that renders the participant at high risk for treatment complications
Ocular Exclusion Criteria for Either Eye
- Suspected or active ocular or periocular infection of either eye
- Any history uveitis including idiopathic, drug-associated or autoimmune-associated uveitis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Comparator Arm PDS Implant Pre-Filled with 100 mg/mL Ranibizumab Participants randomized to the comparator arm will undergo study visits every 4 weeks (Q4W) for comprehensive clinical monitoring until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q36W thereafter. Participants will be eligible to receive intravitreal ranibizumab 0.5 mg injections if treatment eligibility criteria are met. PDS Arm Intravitreal Ranibizumab 0.5 mg Injection Participants randomized to the PDS arm will receive two intravitreal ranibizumab injections 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 36-weeks (Q36W) thereafter Comparator Arm Intravitreal Ranibizumab 0.5 mg Injection Participants randomized to the comparator arm will undergo study visits every 4 weeks (Q4W) for comprehensive clinical monitoring until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q36W thereafter. Participants will be eligible to receive intravitreal ranibizumab 0.5 mg injections if treatment eligibility criteria are met. PDS Arm PDS Implant Pre-Filled with 100 mg/mL Ranibizumab Participants randomized to the PDS arm will receive two intravitreal ranibizumab injections 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 36-weeks (Q36W) thereafter
- Primary Outcome Measures
Name Time Method Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS at Week 52 Week 52 ETDRS = Early Treatment Diabetic Retinopathy Study
DRSS = Diabetic Retinopathy Severity Scale
The ETDRS-DRSS includes 13 score levels, ranging from the absence of retinopathy to PDR, including neovascularization and/or vitreous/preretinal hemorrhage.
- Secondary Outcome Measures
Name Time Method Time to first development of a ≥ 2-step worsening from baseline on the ETDRS-DRSS Baseline up to Week 112 Percentage of participants with adverse device effects Baseline up to Week 112 Percentage of participants with a BCVA score of 69 letters (20/40 approximate Snellen equivalent) or better over time Baseline up to Week 112 Change from baseline in total macular volume as measured on SD-OCT over time Baseline up to Week 112 Incidence, severity, and duration of ocular adverse events of special interest during the postoperative period (≤ 37 days after initial implant insertion) and follow-up period (> 37 days after implant insertion surgery) Baseline up to Week 112 Prevalence of anti-drug antibodies (ADAs) prior to study treatment and incidence of ADAs after study treatment Baseline up to Week 112 Percentage of participants who report preferring PDS treatment to intravitreal ranibizumab treatment, as measured by the PPPQ at Week 52 Week 52 Percentage of participants with a ≥ 3-step improvement from baseline on the ETDRS-DRSS at Week 52 Week 52 Rate of participants developing a ≥ 3-step worsening from baseline on the ETDRS-DRSS through Week 52 Baseline up to 52 weeks Incidence and severity of ocular adverse events Baseline up to Week 112 Pharmacokinetic (PK) parameter value area under the concentration- time curve Baseline up to Week 112 Time to first development of CI-DME Baseline up to Week 112 Change from baseline in Best-Corrected Visual Acuity (BCVA) as measured on the ETDRS chart over time Baseline up to Week 112 A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.
Rate of participants developing PDR or ASNV through Week 52 From baseline through 52 weeks Rate of participants developing a ≥ 2-step worsening from baseline on the ETDRS-DRSS through Week 52 From baseline through 52 weeks Incidence and severity of non-ocular adverse events Baseline up to Week 112 Prevalence of neutralizing antibodies at baseline and incidence of neutralizing antibodies during the study Baseline up to Week 112 Reported incidence of device deficiencies Baseline up to Week 52 Rate of participants developing a vision-threatening complication (defined as PDR, ASNV, or CI-DME [defined as central foveal thickness [CST] ≥325 μm on spectral-domain optical coherence tomography [SD-OCT]) through Week 52 From baseline through 52 weeks PDR = proliferative diabetic retinopathy ASNV = Anterior segment neovascularization
Rate of participants developing CI-DME through Week 52 From baseline through 52 weeks Percentage of participants with a ≥ 2-step improvement from baseline on the ETDRS-DRSS over time Baseline up to Week 112 Percentage of participants with a ≥ 3-step improvement from baseline on the ETDRS-DRSS over time Baseline up to Week 112 Time to first development of either PDR, ASNV, or CI-DME Baseline up to Week 112 Time to first development of PDR or ASNV Baseline up to Week 112 Time to first development of a ≥ 3-step worsening from baseline on the ETDRS-DRSS Baseline up to Week 112 Percentage of participants who lose <15, < 10 and < 5 letters in BCVA from baseline over time Baseline up to Week 112 Change from baseline in CST as measured on SD-OCT over time Baseline up to Week 112 Incidence, severity, and duration of adverse events of special interest Baseline up to Week 112 Serum concentration of ranibizumab observed over time Baseline up to Week 112 PK Parameter minimum serum concentration (Cmin) Baseline up to Week 112 Percentage of participants who do not undergo supplemental treatment with intravitreal ranibizumab within each refill-exchange interval Baseline up to Week 112 Percentage of participants with serious adverse device effects Baseline up to Week 112 Percentage of participants with absence of intraretinal fluid, subretinal fluid or both (as measured in the central 1 mm subfield) over time Baseline up to Week 112 PK parameter half-life (t1/2) after PDS implant insertion Baseline up to Week 112
Trial Locations
- Locations (64)
Retinal Consultants of Arizona;Opthalmology
🇺🇸Phoenix, Arizona, United States
Retina Consultants of Orange County;Clinical Research
🇺🇸Fullerton, California, United States
Jules Stein Eye Institute/ UCLA
🇺🇸Los Angeles, California, United States
California Eye Specialists Medical Group
🇺🇸Pasadena, California, United States
Kaiser Permanente;RESEARCH AND EVALUATION
🇺🇸Riverside, California, United States
Retina Consultants Medical Group
🇺🇸Sacramento, California, United States
Orange County Retina Medical Group
🇺🇸Santa Ana, California, United States
Southwest Retina Research Center
🇺🇸Durango, Colorado, United States
Colorado Clinical Research
🇺🇸Lakewood, Colorado, United States
Georgia Retina
🇺🇸Marietta, Georgia, United States
Retina Consultants of Hawaii at Pali Momi Medical Center
🇺🇸'Aiea, Hawaii, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
University Retina
🇺🇸Lemont, Illinois, United States
Johns Hopkins Hospital;Johns Hopkins Med;Wilmer Eye Inst
🇺🇸Baltimore, Maryland, United States
Cumberland Valley Retina Consultants;Clinical Research
🇺🇸Hagerstown, Maryland, United States
Associated Retinal Consultants - Royal Oak
🇺🇸Royal Oak, Michigan, United States
Retina Associates of Florida;Retina Associates of Florida
🇺🇸Tampa, Florida, United States
VitreoRetinal Surgery PLLC;DBA Retina Consultants of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Pepose Vision Institute
🇺🇸Chesterfield, Missouri, United States
Retina Associates of New Jersey
🇺🇸Teaneck, New Jersey, United States
Retina Vitreous Surgeons of Central New York
🇺🇸Liverpool, New York, United States
New York University (NYU)
🇺🇸New York, New York, United States
Asheville Eye Associates Western Carolina Retinal Associates;Clinical Research
🇺🇸Asheville, North Carolina, United States
Charlotte Eye Ear Nose and Throat Associates- SouthPark;Retina
🇺🇸Charlotte, North Carolina, United States
Ohio State Havener Eye Institute;Ophthalmology Research
🇺🇸Columbus, Ohio, United States
Retina Vitreous Center - Glen Eagles
🇺🇸Edmond, Oklahoma, United States
Retina Northwest;Research Department
🇺🇸Portland, Oregon, United States
Mid Atlantic Retina;Retina Research
🇺🇸Philadelphia, Pennsylvania, United States
Charleston Neuroscience
🇺🇸Ladson, South Carolina, United States
Charles Retina Institution;Retina surgery
🇺🇸Germantown, Tennessee, United States
Tennessee Retina
🇺🇸Nashville, Tennessee, United States
Retina Research Institute of Texas
🇺🇸Abilene, Texas, United States
Austin Retina Associates;Opthalmology
🇺🇸Austin, Texas, United States
Texas Retina Associates;Research
🇺🇸Dallas, Texas, United States
Medical Center Ophthalmology Associates
🇺🇸San Antonio, Texas, United States
Rocky Mountain Retina Consultants
🇺🇸Murray, Utah, United States
Retina Associates of Utah, PLLC;Clinical Research
🇺🇸Salt Lake City, Utah, United States
Wagner Kapoor Institute;Opthalmology
🇺🇸Norfolk, Virginia, United States
Pacific Northwest Retina
🇺🇸Silverdale, Washington, United States
Spokane Eye Clinical Research;Spokane Eye Surgery Center
🇺🇸Spokane, Washington, United States
Emanuelli Research & Development Center
🇵🇷Arecibo, Puerto Rico
Barnet Dulaney Perkins Eye Center
🇺🇸Mesa, Arizona, United States
Associated Retina Consultants
🇺🇸Phoenix, Arizona, United States
California Retina Consultants
🇺🇸Bakersfield, California, United States
The Retina Partners
🇺🇸Encino, California, United States
Retina Group of New England
🇺🇸Waterford, Connecticut, United States
Retina Specialty Institute
🇺🇸Pensacola, Florida, United States
Fort Lauderdale Eye Institute
🇺🇸Plantation, Florida, United States
Southeast Retina Center
🇺🇸Augusta, Georgia, United States
Illinois Retina Associates
🇺🇸Joliet, Illinois, United States
Retina Associates
🇺🇸Lenexa, Kansas, United States
Maine Eye Center
🇺🇸Portland, Maine, United States
The Retina Care Center
🇺🇸Baltimore, Maryland, United States
Sierra Eye Associates
🇺🇸Reno, Nevada, United States
Envision Ocular, LLC
🇺🇸Bloomfield, New Jersey, United States
Duke Eye Center
🇺🇸Durham, North Carolina, United States
Cape Fear Retinal Associates
🇺🇸Wilmington, North Carolina, United States
Palmetto Retina Center
🇺🇸West Columbia, South Carolina, United States
Southeastern Retina Associates
🇺🇸Knoxville, Tennessee, United States
Retina & Vitreous of Texas
🇺🇸Bellaire, Texas, United States
Retina Center of Texas
🇺🇸Grapevine, Texas, United States
Retina Consultants of Texas
🇺🇸Houston, Texas, United States
Piedmont Eye Center
🇺🇸Lynchburg, Virginia, United States
Retina Institute of Virginia
🇺🇸Richmond, Virginia, United States