Clinical trial NCT04503551: 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
Official title: A Phase III, Multicenter, Randomized Study of the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Patients With Diabetic Retinopathy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Diabetic Retinopathy
Keywords: Port Delivery System; ranibizumab; Diabetic Retinopathy; anti-VEGF, nonproliferative diabetic retinopathy, retina, vision loss, retinal disease, eye disease
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-08-07
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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 ≤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)

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS at Week 52
timeFrame: Week 52
Secondary outcomes:
measure: 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
timeFrame: From baseline through 52 weeks
measure: Rate of participants developing PDR or ASNV through Week 52
timeFrame: From baseline through 52 weeks
measure: Rate of participants developing CI-DME through Week 52
timeFrame: From baseline through 52 weeks
measure: Rate of participants developing a ≥ 2-step worsening from baseline on the ETDRS-DRSS through Week 52
timeFrame: From baseline through 52 weeks
measure: Percentage of participants with a ≥ 3-step improvement from baseline on the ETDRS-DRSS at Week 52
timeFrame: Week 52
measure: Rate of participants developing a ≥ 3-step worsening from baseline on the ETDRS-DRSS through Week 52
timeFrame: Baseline up to 52 weeks
measure: Percentage of participants with a ≥ 2-step improvement from baseline on the ETDRS-DRSS over time
timeFrame: Baseline up to Week 112
measure: Percentage of participants with a ≥ 3-step improvement from baseline on the ETDRS-DRSS over time
timeFrame: Baseline up to Week 112
measure: Time to first development of either PDR, ASNV, or CI-DME
timeFrame: Baseline up to Week 112
measure: Time to first development of PDR or ASNV
timeFrame: Baseline up to Week 112
measure: Time to first development of CI-DME
timeFrame: Baseline up to Week 112
measure: Time to first development of a ≥ 2-step worsening from baseline on the ETDRS-DRSS
timeFrame: Baseline up to Week 112
measure: Time to first development of a ≥ 3-step worsening from baseline on the ETDRS-DRSS
timeFrame: Baseline up to Week 112
measure: Change from baseline in Best-Corrected Visual Acuity (BCVA) as measured on the ETDRS chart over time
timeFrame: Baseline up to Week 112
measure: Percentage of participants who lose <15, < 10 and < 5 letters in BCVA from baseline over time
timeFrame: Baseline up to Week 112
measure: Percentage of participants with a BCVA score of 69 letters (20/40 approximate Snellen equivalent) or better over time
timeFrame: Baseline up to Week 112
measure: Change from baseline in CST as measured on SD-OCT over time
timeFrame: Baseline up to Week 112
measure: Change from baseline in total macular volume as measured on SD-OCT over time
timeFrame: Baseline up to Week 112
measure: Incidence and severity of ocular adverse events
timeFrame: Baseline up to Week 112
measure: Incidence and severity of non-ocular adverse events
timeFrame: Baseline up to Week 112
measure: Incidence, severity, and duration of adverse events of special interest
timeFrame: Baseline up to Week 112
measure: 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)
timeFrame: Baseline up to Week 112
measure: Serum concentration of ranibizumab observed over time
timeFrame: Baseline up to Week 112
measure: Pharmacokinetic (PK) parameter value area under the concentration- time curve
timeFrame: Baseline up to Week 112
measure: PK Parameter minimum serum concentration (Cmin)
timeFrame: Baseline up to Week 112
measure: PK parameter half-life (t1/2) after PDS implant insertion
timeFrame: Baseline up to Week 112
measure: Prevalence of anti-drug antibodies (ADAs) prior to study treatment and incidence of ADAs after study treatment
timeFrame: Baseline up to Week 112
measure: Prevalence of neutralizing antibodies at baseline and incidence of neutralizing antibodies during the study
timeFrame: Baseline up to Week 112
measure: Percentage of participants who do not undergo supplemental treatment with intravitreal ranibizumab within each refill-exchange interval
timeFrame: Baseline up to Week 112
measure: Percentage of participants with adverse device effects
timeFrame: Baseline up to Week 112
measure: Percentage of participants with serious adverse device effects
timeFrame: Baseline up to Week 112
measure: Percentage of participants with absence of intraretinal fluid, subretinal fluid or both (as measured in the central 1 mm subfield) over time
timeFrame: Baseline up to Week 112
measure: Percentage of participants who report preferring PDS treatment to intravitreal ranibizumab treatment, as measured by the PPPQ at Week 52
timeFrame: Week 52
measure: Reported incidence of device deficiencies
timeFrame: Baseline up to Week 52
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Barnet Dulaney Perkins Eye Center
state: Arizona
city: Phoenix
country: United States
facility: Retinal Consultants of Arizona;Opthalmology
state: Arizona
city: Phoenix
country: United States
facility: Associated Retina Consultants
state: Arizona
city: Bakersfield
country: United States
facility: California Retina Consultants
state: California
city: Encino
country: United States
facility: The Retina Partners
state: California
city: Fullerton
country: United States
facility: Retina Consultants of Orange County;Clinical Research
state: California
city: Los Angeles
country: United States
facility: Jules Stein Eye Institute/ UCLA
state: California
city: Pasadena
country: United States
facility: California Eye Specialists Medical Group
state: California
city: Riverside
country: United States
facility: Kaiser Permanente;RESEARCH AND EVALUATION
state: California
city: Sacramento
country: United States
facility: Retina Consultants Medical Group
state: California
city: Santa Ana
country: United States
facility: Orange County Retina Medical Group
state: California
city: Durango
country: United States
facility: Southwest Retina Research Center
state: Colorado
city: Lakewood
country: United States
facility: Colorado Clinical Research
state: Colorado
city: Waterford
country: United States
facility: Retina Group of New England
state: Connecticut
city: Pensacola
country: United States
facility: Retina Specialty Institute
state: Florida
city: Plantation
country: United States
facility: Fort Lauderdale Eye Institute
state: Florida
city: Tampa
country: United States
facility: Retina Associates of Florida;Retina Associates of Florida
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Marietta
country: United States
facility: Georgia Retina
state: Georgia
city: 'Aiea
country: United States
facility: Retina Consultants of Hawaii at Pali Momi Medical Center
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Joliet
country: United States
facility: Illinois Retina Associates
state: Illinois
city: Lemont
country: United States
facility: University Retina
state: Illinois
city: Lenexa
country: United States
facility: Retina Associates
state: Kansas
city: Portland
country: United States
facility: Maine Eye Center
state: Maine
city: Baltimore
country: United States
facility: The Retina Care Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital;Johns Hopkins Med;Wilmer Eye Inst
state: Maryland
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants;Clinical Research
state: Maryland
city: Royal Oak
country: United States
facility: Associated Retinal Consultants - Royal Oak
state: Michigan
city: Minneapolis
country: United States
facility: VitreoRetinal Surgery PLLC;DBA Retina Consultants of Minnesota
state: Minnesota
city: Chesterfield
country: United States
facility: Pepose Vision Institute
state: Missouri
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Bloomfield
country: United States
facility: Envision Ocular, LLC
state: New Jersey
city: Teaneck
country: United States
facility: Retina Associates of New Jersey
state: New Jersey
city: Liverpool
country: United States
facility: Retina Vitreous Surgeons of Central New York
state: New York
city: New York
country: United States
facility: New York University (NYU)
state: New York
city: Asheville
country: United States
facility: Asheville Eye Associates Western Carolina Retinal Associates;Clinical Research
state: North Carolina
city: Charlotte
country: United States
facility: Charlotte Eye Ear Nose and Throat Associates- SouthPark;Retina
state: North Carolina
city: Durham
country: United States
facility: Duke Eye Center
state: North Carolina
city: Wilmington
country: United States
facility: Cape Fear Retinal Associates
state: North Carolina
city: Columbus
country: United States
facility: Ohio State Havener Eye Institute;Ophthalmology Research
state: Ohio
city: Edmond
country: United States
facility: Retina Vitreous Center - Glen Eagles
state: Oklahoma
city: Portland
country: United States
facility: Retina Northwest;Research Department
state: Oregon
city: Philadelphia
country: United States
facility: Mid Atlantic Retina;Retina Research
state: Pennsylvania
city: Ladson
country: United States
facility: Charleston Neuroscience
state: South Carolina
city: West Columbia
country: United States
facility: Palmetto Retina Center
state: South Carolina
city: Germantown
country: United States
facility: Charles Retina Institution;Retina surgery
state: Tennessee
city: Knoxville
country: United States
facility: Southeastern Retina Associates
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Retina
state: Tennessee
city: Abilene
country: United States
facility: Retina Research Institute of Texas
state: Texas
city: Austin
country: United States
facility: Austin Retina Associates;Opthalmology
state: Texas
city: Bellaire
country: United States
facility: Retina & Vitreous of Texas
state: Texas
city: Dallas
country: United States
facility: Texas Retina Associates;Research
state: Texas
city: Grapevine
country: United States
facility: Retina Center of Texas
state: Texas
city: Houston
country: United States
facility: Retina Consultants of Texas
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
city: Murray
country: United States
facility: Rocky Mountain Retina Consultants
state: Utah
city: Salt Lake City
country: United States
facility: Retina Associates of Utah, PLLC;Clinical Research
state: Utah
city: Lynchburg
country: United States
facility: Piedmont Eye Center
state: Virginia
city: Norfolk
country: United States
facility: Wagner Kapoor Institute;Opthalmology
state: Virginia
city: Richmond
country: United States
facility: Retina Institute of Virginia
state: Virginia
city: Silverdale
country: United States
facility: Pacific Northwest Retina
state: Washington
city: Spokane
country: United States
facility: Spokane Eye Clinical Research;Spokane Eye Surgery Center
state: Washington
city: Arecibo
country: Puerto Rico
facility: Emanuelli Research & Development Center
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: