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

Diabetic Retinopathy Clinical Trial

— PAVILION  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04503551
• Other study ID #: GR41675
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 10, 2020
• Est. completion date: May 7, 2024

Study information

• Verified date: September 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 174
• Est. completion date: May 7, 2024
• Est. primary completion date: October 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Retinopathy
• Retinal Diseases

Intervention

Drug:
• PDS Implant Pre-Filled with 100 mg/mL Ranibizumab
Will be administered as per the schedule described in individual arm.
• Intravitreal Ranibizumab 0.5 mg Injection
Will be administered as per the schedule described in individual arm.

Locations

Country	Name	City	State
Puerto Rico	Emanuelli Research and Development Center LLC	Arecibo
United States	Retina Consultants of Hawaii	'Aiea	Hawaii
United States	Western Carolina Retinal Associate PA	Asheville	North Carolina
United States	Southeast Retina Center	Augusta	Georgia
United States	Austin Retina Associates	Austin	Texas
United States	California Retina Consultants	Bakersfield	California
United States	The Retina Care Center	Baltimore	Maryland
United States	Retina & Vitreous of Texas	Bellaire	Texas
United States	Envision Ocular, LLC	Bloomfield	New Jersey
United States	Cumberland Valley Retina Consultants; Chambersburg	Chambersburg	Pennsylvania
United States	Char Eye Ear &Throat Assoc	Charlotte	North Carolina
United States	Midwest Vision Research Foundation	Chesterfield	Missouri
United States	Northwestern Medical Group/Northwestern University	Chicago	Illinois
United States	The Ohio State University	Columbus	Ohio
United States	Texas Retina Associates	Dallas	Texas
United States	Southwest Retina Consultants	Durango	Colorado
United States	Duke Eye Center	Durham	North Carolina
United States	Retina Vitreous Center	Edmond	Oklahoma
United States	The Retina Partners	Encino	California
United States	Retina Consultants of Orange County	Fullerton	California
United States	Charles Retina Institute	Germantown	Tennessee
United States	Cumberland Valley Retina Associates	Hagerstown	Maryland
United States	Illinois Retina Associates	Joliet	Illinois
United States	Southeastern Retina Associates	Knoxville	Tennessee
United States	Charleston Neuroscience Inst	Ladson	South Carolina
United States	Colorado Retina Associates, PC	Lakewood	Colorado
United States	Retina Associates	Lenexa	Kansas
United States	Retina Vit Surgeons/Central NY	Liverpool	New York
United States	Piedmont Eye Center	Lynchburg	Virginia
United States	Georgia Retina PC	Marietta	Georgia
United States	Barnet Dulaney Perkins Eye Center	Mesa	Arizona
United States	Vitreo Retinal Surgery	Minneapolis	Minnesota
United States	Tennessee Retina PC	Nashville	Tennessee
United States	New York University	New York	New York
United States	California Eye Specialists Medical group Inc.	Pasadena	California
United States	Retina Specialty Institute	Pensacola	Florida
United States	Mid Atlantic Retina - Wills Eye Hospital	Philadelphia	Pennsylvania
United States	Associated Retina Consultants	Phoenix	Arizona
United States	Fort Lauderdale Eye Institute	Plantation	Florida
United States	Maine Eye Center	Portland	Maine
United States	Sierra Eye Associates	Reno	Nevada
United States	Retina Institute of Virginia	Richmond	Virginia
United States	Kaiser Permanente Riverside Medical Center	Riverside	California
United States	Associated Retinal Consultants PC	Royal Oak	Michigan
United States	Retinal Consultants Med Group	Sacramento	California
United States	Rocky Mountain Retina	Salt Lake City	Utah
United States	Med Center Ophthalmology Assoc	San Antonio	Texas
United States	Orange County Retina Med Group	Santa Ana	California
United States	California Retina Consultants	Santa Barbara	California
United States	Retina Center Northwest	Silverdale	Washington
United States	Retina Center of Texas	Southlake	Texas
United States	Spokane Eye Clinical Research	Spokane	Washington
United States	Retina Associates of Florida, LLC	Tampa	Florida
United States	Retina Associates of NJ	Teaneck	New Jersey
United States	Retina Consultants of Texas	The Woodlands	Texas
United States	Retina Specialists	Towson	Maryland
United States	Retina Group of New England	Waterford	Connecticut
United States	Palmetto Retina Center	West Columbia	South Carolina
United States	Wolfe Eye Clinic	West Des Moines	Iowa
United States	Cape Fear Retinal Associates	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with a =2-step improvement from baseline on the ETDRS-DRSS at 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.	Week 52
Secondary	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	PDR = proliferative diabetic retinopathy ASNV = Anterior segment neovascularization	From baseline through 52 weeks
Secondary	Rate of participants developing PDR or ASNV through Week 52		From baseline through 52 weeks
Secondary	Rate of participants developing CI-DME through Week 52		From baseline through 52 weeks
Secondary	Rate of participants developing a = 2-step worsening from baseline on the ETDRS-DRSS through Week 52		From baseline through 52 weeks
Secondary	Percentage of participants with a = 3-step improvement from baseline on the ETDRS-DRSS at Week 52		Week 52
Secondary	Rate of participants developing a = 3-step worsening from baseline on the ETDRS-DRSS through Week 52		Baseline up to 52 weeks
Secondary	Percentage of participants with a = 2-step improvement from baseline on the ETDRS-DRSS over time		Baseline up to Week 112
Secondary	Percentage of participants with a = 3-step improvement from baseline on the ETDRS-DRSS over time		Baseline up to Week 112
Secondary	Time to first development of either PDR, ASNV, or CI-DME		Baseline up to Week 112
Secondary	Time to first development of PDR or ASNV		Baseline up to Week 112
Secondary	Time to first development of CI-DME		Baseline up to Week 112
Secondary	Time to first development of a = 2-step worsening from baseline on the ETDRS-DRSS		Baseline up to Week 112
Secondary	Time to first development of a = 3-step worsening from baseline on the ETDRS-DRSS		Baseline up to Week 112
Secondary	Change from baseline in Best-Corrected Visual Acuity (BCVA) as measured on the ETDRS chart over time	A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.	Baseline up to Week 112
Secondary	Percentage of participants who lose <15, < 10 and < 5 letters in BCVA from baseline over time		Baseline up to Week 112
Secondary	Percentage of participants with a BCVA score of 69 letters (20/40 approximate Snellen equivalent) or better over time		Baseline up to Week 112
Secondary	Change from baseline in CST as measured on SD-OCT over time		Baseline up to Week 112
Secondary	Change from baseline in total macular volume as measured on SD-OCT over time		Baseline up to Week 112
Secondary	Incidence and severity of ocular adverse events		Baseline up to Week 112
Secondary	Incidence and severity of non-ocular adverse events		Baseline up to Week 112
Secondary	Incidence, severity, and duration of adverse events of special interest		Baseline up to Week 112
Secondary	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
Secondary	Serum concentration of ranibizumab observed over time		Baseline up to Week 112
Secondary	Pharmacokinetic (PK) parameter value area under the concentration- time curve		Baseline up to Week 112
Secondary	PK Parameter minimum serum concentration (Cmin)		Baseline up to Week 112
Secondary	PK parameter half-life (t1/2) after PDS implant insertion		Baseline up to Week 112
Secondary	Prevalence of anti-drug antibodies (ADAs) prior to study treatment and incidence of ADAs after study treatment		Baseline up to Week 112
Secondary	Prevalence of neutralizing antibodies at baseline and incidence of neutralizing antibodies during the study		Baseline up to Week 112
Secondary	Percentage of participants who do not undergo supplemental treatment with intravitreal ranibizumab within each refill-exchange interval		Baseline up to Week 112
Secondary	Percentage of participants with adverse device effects		Baseline up to Week 112
Secondary	Percentage of participants with serious adverse device effects		Baseline up to Week 112
Secondary	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
Secondary	Percentage of participants who report preferring PDS treatment to intravitreal ranibizumab treatment, as measured by the PPPQ at Week 52		Week 52
Secondary	Reported incidence of device deficiencies		Baseline up to Week 52