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 (PAVILION)

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 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

Study Overview

• Status: Completed
• Conditions: Diabetic Retinopathy
• Intervention / Treatment: Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab; Drug: Intravitreal Ranibizumab 0.5 mg Injection

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Arecibo, Puerto Rico, 612
    • Emanuelli Research & Development Center
• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Barnet Dulaney Perkins Eye Center
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants
    • Phoenix, Arizona, United States, 85014
      • Retinal Consultants of Arizona;Opthalmology
  • California
    • Bakersfield, California, United States, 93309
      • California Retina Consultants
    • Encino, California, United States, 91436
      • The Retina Partners
    • Fullerton, California, United States, 92835
      • Retina Consultants of Orange County;Clinical Research
    • Los Angeles, California, United States, 90095
      • Jules Stein Eye Institute/ UCLA
    • Pasadena, California, United States, 91107
      • California Eye Specialists Medical Group
    • Riverside, California, United States, 92505
      • Kaiser Permanente;RESEARCH AND EVALUATION
    • Sacramento, California, United States, 95841
      • Retina Consultants Medical Group
    • Santa Ana, California, United States, 92705
      • Orange County Retina Medical Group
  • Colorado
    • Durango, Colorado, United States, 81303
      • Southwest Retina Research Center
    • Lakewood, Colorado, United States, 80228
      • Colorado Clinical Research
  • Connecticut
    • Waterford, Connecticut, United States, 06385
      • Retina Group of New England
  • Florida
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
    • Plantation, Florida, United States, 33324
      • Fort Lauderdale Eye Institute
    • Tampa, Florida, United States, 33609
      • Retina Associates of Florida;Retina Associates of Florida
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
    • Marietta, Georgia, United States, 30060
      • Georgia Retina
  • Hawaii
    • ‘Aiea, Hawaii, United States, 96701
      • Retina Consultants of Hawaii at Pali Momi Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
    • Joliet, Illinois, United States, 60435
      • Illinois Retina Associates
    • Lemont, Illinois, United States, 60439
      • University Retina
  • Kansas
    • Lenexa, Kansas, United States, 66215
      • Retina Associates
  • Maine
    • Portland, Maine, United States, 04605
      • Maine Eye Center
  • Maryland
    • Baltimore, Maryland, United States, 21209
      • The Retina Care Center
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital;Johns Hopkins Med;Wilmer Eye Inst
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants;Clinical Research
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Associated Retinal Consultants - Royal Oak
  • Minnesota
    • Minneapolis, Minnesota, United States, 55435
      • VitreoRetinal Surgery PLLC;DBA Retina Consultants of Minnesota
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Pepose Vision Institute
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • Envision Ocular, LLC
    • Teaneck, New Jersey, United States, 07666
      • Retina Associates of New Jersey
  • New York
    • Liverpool, New York, United States, 13088
      • Retina Vitreous Surgeons of Central New York
    • New York, New York, United States, 10012
      • New York University (NYU)
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Asheville Eye Associates Western Carolina Retinal Associates;Clinical Research
    • Charlotte, North Carolina, United States, 28210
      • Charlotte Eye Ear Nose and Throat Associates- SouthPark;Retina
    • Durham, North Carolina, United States, 27705
      • Duke Eye Center
    • Wilmington, North Carolina, United States, 28401
      • Cape Fear Retinal Associates
  • Ohio
    • Columbus, Ohio, United States, 43212
      • Ohio State Havener Eye Institute;Ophthalmology Research
  • Oklahoma
    • Edmond, Oklahoma, United States, 73013
      • Retina Vitreous Center - Glen Eagles
  • Oregon
    • Portland, Oregon, United States, 97221
      • Retina Northwest;Research Department
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Mid Atlantic Retina;Retina Research
  • South Carolina
    • Ladson, South Carolina, United States, 29456
      • Charleston Neuroscience
    • West Columbia, South Carolina, United States, 29169
      • Palmetto Retina Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Charles Retina Institution;Retina surgery
    • Knoxville, Tennessee, United States, 37922
      • Southeastern Retina Associates
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Austin, Texas, United States, 78705
      • Austin Retina Associates;Opthalmology
    • Bellaire, Texas, United States, 77401
      • Retina & Vitreous of Texas
    • Dallas, Texas, United States, 75231
      • Texas Retina Associates;Research
    • Grapevine, Texas, United States, 76051
      • Retina Center Of Texas
    • Houston, Texas, United States, 77401
      • Retina Consultants of Texas
    • San Antonio, Texas, United States, 78240
      • Medical Center Ophthalmology Associates
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Texas
  • Utah
    • Murray, Utah, United States, 84107
      • Rocky Mountain Retina Consultants
    • Salt Lake City, Utah, United States, 84107
      • Retina Associates of Utah, PLLC;Clinical Research
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Piedmont Eye Center
    • Norfolk, Virginia, United States, 23502
      • Wagner Kapoor Institute;Opthalmology
    • Richmond, Virginia, United States, 23235
      • Retina Institute of Virginia
  • Washington
    • Silverdale, Washington, United States, 98383
      • Pacific Northwest Retina
    • Spokane, Washington, United States, 99204
      • Spokane Eye Clinical Research;Spokane Eye Surgery Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PDS Arm; 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	Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab; Will be administered as per the schedule described in individual arm.; Drug: Intravitreal Ranibizumab 0.5 mg Injection; Will be administered as per the schedule described in individual arm.
Other: Comparator Arm; 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.	Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab; Will be administered as per the schedule described in individual arm.; Drug: Intravitreal Ranibizumab 0.5 mg Injection; Will be administered as per the schedule described in individual arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a ≥2-Step Improvement From Baseline on the Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale (ETDRS-DRSS) at Week 52	ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy. The Cochran-Mantel Haenszel (CMH) method was used for analysis and weighted percentage of participants are estimated and reported in this outcome measure. Participants receiving supplemental treatments, prohibited therapy, or panretinal photocoagulation (PRP) were considered non-responders. Missing values not preceded by these intercurrent events were imputed using the last observation carried forward method. SD OCT= spectral-domain optical coherence tomography.	Baseline, Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Participants Developing a Vision-Threatening Complication or Center-involved Diabetic Macular Edema (CI-DME) Through Week 52	A vision threatening complication is defined as proliferative DR (PDR) or anterior segment neovascularization (ASNV) or center-involved diabetic macular edema (CI-DME). CI-DME is defined as central foveal thickness (CST) ≥325 micrometres (μm) on spectral-domain optical coherence tomography (SD-OCT). Composite strategy (i.e., considered to be an event) was applied to participants who received supplemental or prohibited therapy or PRP in the study eye. The rate of participants was calculated using the Kaplan-Meier (KM) method.	From Baseline through Week 52
Rate of Participants Developing PDR or ASNV Through Week 52	The KM method was used for analysis, and estimates are in terms of event rate. Composite strategy (i.e., considered to be an event) was applied to participants who received supplemental or prohibited therapy or PRP in the study eye.	From Baseline through Week 52
Rate of Participants Developing CI-DME Through Week 52	CI-DME is defined as CST ≥325 μm on SD-OCT. The KM method was used for analysis, and estimated in terms of event rate. Composite strategy (i.e., considered to be an event) was applied to participants who received supplemental or prohibited therapy or PRP in the study eye.	From Baseline through Week 52
Rate of Participants Developing a ≥ 2-Step Worsening From Baseline on the ETDRS-DRSS Through Week 52	ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR ), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy. Composite strategy (i.e., considered to be an event) was applied to participants who received supplemental or prohibited therapy or PRP in the study eye. The rate of participants developing ≥ 2-step worsening on the ETDRS-DRSS was calculated using the KM method.	From Baseline through Week 52
Percentage of Participants With a ≥ 3-Step Improvement From Baseline on the ETDRS-DRSS at Week 52	ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR ), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy. Participants receiving supplemental treatments, prohibited therapy, or panretinal photocoagulation (PRP) were considered non-responders. Missing values not preceded by these intercurrent events were imputed using the last observation carried forward method. Percentages are rounded off to the nearest decimal point.	Week 52
Rate of Participants Developing a ≥ 3-Step Worsening From Baseline on the ETDRS-DRSS Through Week 52	ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR ), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy. Composite strategy (i.e., considered to be an event) was applied to participants who received supplemental or prohibited therapy or PRP in the study eye. The rate of participants developing ≥ 3-step worsening on the ETDRS-DRSS was calculated using the KM method.	From Baseline through Week 52
Percentage of Participants With a ≥ 2-Step Improvement From Baseline on the ETDRS-DRSS Over Time	ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale , from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy.	Baseline up to Week 112
Percentage of Participants With a ≥ 3-step Improvement From Baseline on the ETDRS-DRSS Over Time	ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR ), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale , from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy.	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 CI-DME	CI-DME is defined as CST ≥325 μm on SD-OCT.	Baseline up to Week 112
Time to First Development of a ≥ 2-Step Worsening From Baseline on the ETDRS-DRSS	ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy.	Baseline up to Week 112
Time to First Development of a ≥ 3-Step Worsening From Baseline on the ETDRS-DRSS	ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy.	Baseline up to Week 112
Change From Baseline in Best-Corrected Visual Acuity (BCVA) as Measured on the ETDRS Chart Over Time	BCVA was measured at a starting test distance of 4 meters using a set of three Precision Vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R). The BCVA letter score ranges from 0 to 100 (best score attainable), and a higher score indicates better visual acuity.	Baseline up to Week 112
Percentage of Participants Who Lost <15, <10 and <5 Letters in BCVA From Baseline Over Time	BCVA was measured at a starting test distance of 4 meters using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R). The BCVA letter score ranges from 0 to 100 (best score attainable), and a higher score indicates better visual acuity.	Baseline up to Week 112
Percentage of Participants With a BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Over Time	BCVA is measured using the ETDRS visual acuity chart starting at a test distance of 4 meters. The number of letters read correctly, Snellen fraction are converted to a decimal scale. There are 11 lines on a standard Snellen chart ranging from 0.1 (20/200) at worst to 2.0 (20/10) at best. 20/20 on the decimal scale is equal to 1.0. The higher the number of letters read correctly (higher number on the decimal scale), the better the vision (or visual acuity). The Snellen equivalent of 20/40 or better is 69 or more letters correctly read in the ETDRS chart.	Baseline up to Week 112
Change From Baseline in CST as Measured on SD-OCT Over Time	CST is defined as the average thickness of the central 1 millimeter (mm) circle of the ETDRS grid centered on the fovea measured between the internal limiting membrane and the Bruch's membrane. CST is measured using spectral domain optical coherence tomography (SD-OCT). A central reading center graded the SD-OCT digital images. A negative change from baseline value represents a reduction in macular edema.	Baseline up to Week 112
Change From Baseline in Total Macular Volume (TMV) as Measured on SD-OCT Over Time	Total macular volume in cubic millimeter (mm^3), is the calculated volume from the layers of the retina based off OCT imaging. TMV is measured using SD-OCT.	Baseline up to Week 112
Number of Participants With Ocular Adverse Events (AEs) and Severity of Ocular AEs in the PDS Arm	An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product,regardless of causal attribution.An adverse event can therefore be any unfavourable & unintended sign,symptom,or disease temporally associated with the use of a pharmaceutical product,whether considered related to the pharmaceutical product.Preexisting conditions which worsen during a study are also considered as adverse events.Ocular AEs are the events which are localized in the ocular region,graded according to the AE Severity Grading Scale as Mild:discomfort noticed,but no disruption of normal daily activity;Moderate:Discomfort sufficient to reduce or affect normal daily activity;Severe incapacitating with inability to work or to perform normal daily activity.Number of participants with ocular AEs in the study eye are reported in this outcome measure.As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only.	From first dose of study drug through Week 52
Number of Participants With Non-ocular AEs in the PDS Arm	An adverse event is any untoward medical occurrence in a clinical investigation participant subject administered a pharmaceutical product, regardless of causal attribution. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only.	From first dose of study drug through Week 52
Number of Participants With At Least One Ocular Adverse Events of Special Interest (AESI) in the PDS Arm	An AE is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Ocular AESI include vitreous hemorrhage; endophthalmitis; retinal detachment; conjunctival retraction; conjunctival erosion; conjunctival bleb or conjunctival filtering bleb leak; hyphema; cataract; device dislocation. As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only.	From first dose of study drug through Week 52
Number of Participants With At Least One Ocular AESI During the Postoperative Period in the PDS Arm	An AE is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Ocular AESI include vitreous hemorrhage; endophthalmitis; retinal detachment; conjunctival retraction; conjunctival erosion; conjunctival bleb or conjunctival filtering bleb leak; hyphema; cataract; device dislocation. The ocular AESIs in the study eye were categorized based on onset as, Postoperative Period: onset within 37 days post initial implantation. As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only.	From Day 1 to Day 37 Postoperative Period
Serum Concentration of Ranibizumab Observed Over Time		Baseline up to week 112
Pharmacokinetic (PK) Parameter Value Area Under the Concentration		At Baseline and multiple time points up to week 112
Minimum Serum Concentration (Cmin) of Ranibizumab Observed Over Time		Baseline up to week 112
Half-Life (t ½) of Ranibizumab Observed Over Time		Baseline up to Week 112
Number of Participants With Anti-Drug Antibodies (ADAs) to Ranibizumab	The numbers of ADA-positive participants at baseline and after drug administration were to be summarized for participants exposed to Ranibizumab. PDS patients who were ADA positive at the reference visit and ADA titer increased after implant; in this case, the titer of one or more samples collected after implant must be at least 4-fold greater than the titer of the reference visit sample. These patients are considered to have treatment-enhanced ADA responses.	Baseline up to Week 112
Number of Participants With Neutralizing Antibodies to Ranibizumab	The numbers of neutralizing antibodies positive participants at baseline and after drug administration were to be summarized for participants exposed to Ranibizumab.	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 At Least One AE Related to Study Device or Procedure in the PDS Arm	An AE related to study device or procedure is defined as any adverse event related to the use of an investigational medical device. This includes any adverse events resulting from insufficient or inadequate instructions for use, deployment, implantation, installation, operation, or any malfunction of the investigational medical device and any adverse event resulting from use error or from intentional misuse of the investigational medical device. PDS Device refers to the implant, insertion tool, initial fill needle, refill needle, and explant tool. PDS Procedure refers to the initial fill, implant insertion, refill-exchange, and explantation. As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only. Percentages are rounded off to the nearest decimal point.	From first dose of study drug through Week 52
Percentage of Participants With Serious Adverse Effects Related to Study Device or Procedure in the PDS Arm	An AE related to study device or procedure is defined as any AE related to the use of an investigational medical device & includes any AE resulting from insufficient or inadequate instructions for use, deployment, implantation, installation, operation, or any malfunction of the investigational medical device & any AE resulting from use error or from intentional misuse of the investigational medical device. PDS refers to the implant, insertion tool, initial fill needle, refill needle & explant tool. PDS procedure refers to the initial fill, implant insertion, refill-exchange, & explantation. Any AE related to study device or procedure that resulted in any of a serious AE such as death, life-threatening illness or injury or permanent impairment of a body structure or a body function was considered serious. As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only. Percentages are rounded off to the nearest decimal point.	From Day 1 up to Week 52
Percentage of Participants With Absence of Intraretinal Fluid, Subretinal Fluid or Both Over Time	Absence of intraretinal fluid and subretinal fluid are measured in the central 1 mm subfield on SD-OCT. Percentages are rounded off to the nearest decimal point.	Baseline up to Week 112
Percentage of Participants Who Report Preferring PDS Treatment to Intravitreal Ranibizumab Treatment, as Measured by the PDS Patient Preference Questionnaire (PPPQ) at Week 52	The PPPQ is a 3-item questionnaire that captures a participant's preference for treatment (PDS or intravitreal injections), the strength of their preference (very strong, fairly strong, and not very strong) and the reasons for their preference (less worry or nervousness, requires less time for treatment, less discomfort, fewer treatments and other reason). As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only. Percentages are rounded off to the nearest decimal point.	Week 52
Number of Participants With Device Deficiencies	A device deficiency is defined as any inadequacy with respect to labeling, identity, quality, durability, reliability, usability, safety, or performance of an investigational device, including malfunctions, use errors, or inadequacy in information supplied by the manufacturer. As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only and device deficiencies were to be recorded in the electronic capture system (EDC) after implementation of protocol Version 2 (i.e., for participants implanted after 14 June 2021).	Baseline up to Week 52

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Pieramici DJ, Awh CC, Chang M, Emanuelli A, Holekamp NM, Hu AY, Suner IJ, Wykoff CC, Brittain C, Howard D, Quezada-Ruiz C, Santhanakrishnan A, Latkany P. Port Delivery System With Ranibizumab vs Monitoring in Nonproliferative Diabetic Retinopathy Without Macular Edema: The Pavilion Randomized Clinical Trial. JAMA Ophthalmol. 2025 Apr 1;143(4):317-325. doi: 10.1001/jamaophthalmol.2025.0001.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2020
• Primary Completion (Actual): October 3, 2022
• Study Completion (Actual): February 23, 2026

Study Registration Dates

• First Submitted: August 5, 2020
• First Submitted That Met QC Criteria: August 5, 2020
• First Posted (Actual): August 7, 2020

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Port Delivery System; ranibizumab; Diabetic Retinopathy; anti-VEGF, nonproliferative diabetic retinopathy, retina, vision loss, retinal disease, eye disease
• Additional Relevant MeSH Terms: Neurologic Manifestations; Endocrine System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetic Angiopathies; Diabetes Complications; Sensation Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Retinal Diseases; Diabetic Retinopathy; Eye Diseases; Vision Disorders; Amino Acids, Peptides, and Proteins; Proteins; Therapeutics; Drug Administration Routes; Drug Therapy; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Ranibizumab; Injections
• Other Study ID Numbers: GR41675

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No