This Study Will Evaluate the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Participants With Diabetic Macular Edema Compared With Intravitreal Ranibizumab

Diabetic Macular Edema Clinical Trial

— Pagoda  

Official title:

A Phase III, Multicenter, Randomized, Visual Assessor-Masked, Active-comparator Study of the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Patients With Diabetic Macular Edema (Pagoda)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04108156
• Other study ID #: GR40550
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 30, 2019
• Est. completion date: February 28, 2025

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy, safety, and pharmacokinetics of the Port Delivery System with Ranibizumab (PDS) in Participants with Diabetic Macular Edema (DME) when treated every 24 weeks (Q24W) compared with intravitreal ranibizumab 0.5 mg every 4 weeks (Q4W).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 634
• Est. completion date: February 28, 2025
• Est. primary completion date: September 19, 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 =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

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Edema
• Macular Edema

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
United States	Retina Res Institute of Texas	Abilene	Texas
United States	Texas Retina Associates	Arlington	Texas
United States	Western Carolina Retinal Associate PA	Asheville	North Carolina
United States	Southeast Retina Center	Augusta	Georgia
United States	Austin Clinical Research LLC	Austin	Texas
United States	Austin Research Center for Retina	Austin	Texas
United States	Austin Retina Associates	Austin	Texas
United States	California Retina Consultants	Bakersfield	California
United States	Johns Hopkins Med; Wilmer Eye Inst	Baltimore	Maryland
United States	The Retina Care Center	Baltimore	Maryland
United States	Retina & Vitreous of Texas	Bellaire	Texas
United States	Retina-Vitreous Associates Medical Group	Beverly Hills	California
United States	Envision Ocular, LLC	Bloomfield	New Jersey
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Cumberland Valley Retina Consultants; Chambersburg	Chambersburg	Pennsylvania
United States	Char Eye Ear &Throat Assoc	Charlotte	North Carolina
United States	Mid Atlantic Retina	Cherry Hill	New Jersey
United States	Midwest Vision Research Foundation	Chesterfield	Missouri
United States	Retina Group of Washington	Chevy Chase	Maryland
United States	Northwestern Medical Group/Northwestern University	Chicago	Illinois
United States	Cincinnati Eye Institute	Cincinnati	Ohio
United States	Cleveland Clinic Foundation; Cole Eye Institute	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Texas Retina Associates	Dallas	Texas
United States	Midwest Retina	Dublin	Ohio
United States	Duke Eye Center	Durham	North Carolina
United States	Retina Vitreous Center	Edmond	Oklahoma
United States	The Retina Partners	Encino	California
United States	Eye Center of Northern CO	Fort Collins	Colorado
United States	Retina Group of Florida	Fort Lauderdale	Florida
United States	National Ophthalmic Research Institute	Fort Myers	Florida
United States	Texas Retina Associates	Fort Worth	Texas
United States	Retina Consultants of Orange County	Fullerton	California
United States	Charles Retina Institute	Germantown	Tennessee
United States	Associated Retinal Consultants	Grand Rapids	Michigan
United States	Foundation for Vision Research	Grand Rapids	Michigan
United States	Cumberland Valley Retina Associates	Hagerstown	Maryland
United States	Long Is. Vitreoretinal Consult	Hauppauge	New York
United States	Graystone Eye	Hickory	North Carolina
United States	Illinois Retina Associates	Joliet	Illinois
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 Associates of Kentucky	Lexington	Kentucky
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	Carolina Eyecare Physicians	Mount Pleasant	South Carolina
United States	N CA Retina Vitreous Assoc	Mountain View	California
United States	Tennessee Retina PC	Nashville	Tennessee
United States	New York University	New York	New York
United States	Wagner Kapoor Institute	Norfolk	Virginia
United States	University Retina and Macula Associates, PC	Oak Forest	Illinois
United States	East Bay Retina Consultants	Oakland	California
United States	Ophthalmic Cons of Long Island	Oceanside	New York
United States	California Eye Specialists Medical group Inc.	Pasadena	California
United States	Doheny Eye Institute	Pasadena	California
United States	Retina Specialty Institute	Pensacola	Florida
United States	Arizona Retina and Vitreous Consultants	Phoenix	Arizona
United States	Associated Retina Consultants	Phoenix	Arizona
United States	Retinal Consultants of Arizona	Phoenix	Arizona
United States	Fort Lauderdale Eye Institute	Plantation	Florida
United States	Maine Eye Center	Portland	Maine
United States	Retina Northwest	Portland	Oregon
United States	Sierra Eye Associates	Reno	Nevada
United States	Retina Institute of Virginia	Richmond	Virginia
United States	Retinal Consultants Med Group	Sacramento	California
United States	The Retina Institute	Saint Louis	Missouri
United States	Retina Vitreous Assoc of FL	Saint Petersburg	Florida
United States	Retina Associates of Utah, PLLC	Salt Lake City	Utah
United States	Rocky Mountain Retina	Salt Lake City	Utah
United States	Med Center Ophthalmology Assoc	San Antonio	Texas
United States	Zuckerberg San Francisco General Hospital	San Francisco	California
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	Spokane Eye Clinical Research	Spokane	Washington
United States	Southern Vitreoretinal Assoc	Tallahassee	Florida
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, LLC	West Columbia	South Carolina
United States	Wolfe Eye Clinic	West Des Moines	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Baseline to Week 64
Secondary	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	ETDRS-DRSS = ETDRS Diabetic Retinopathy Severity Scale	Baseline to Week 64
Secondary	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
Secondary	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
Secondary	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
Secondary	Change from baseline in BCVA as measured on the ETDRS chart over time		Baseline up to Week 120
Secondary	Percentage of participants who lose <15, <10, and <5 letters in BCVA from baseline over time		Baseline up to Week 120
Secondary	Percentage of participants who gain =15, =10, =5, =0 letters in BCVA from baseline over time		Baseline up to Week 120
Secondary	Percentage of participants with a BCVA Snellen equivalent of 20/40 or better over time		Baseline up to Week 120
Secondary	Percentage of participants with a BCVA Snellen equivalent of 20/200 or worse over time		Baseline up to Week 120
Secondary	Percentage of participants with a =2-step improvement from baseline on the ETDRS-DRSS over time		Baseline up to Week 120
Secondary	Percentage of participants with a =3-step improvement from baseline on the ETDRS-DRSS over time		Baseline up to Week 120
Secondary	Time to =2-step worsening from baseline on the ETDRS-DRSS		Baseline up to Week 120
Secondary	Time to =3-step worsening from baseline on the ETDRS-DRSS		Baseline up to Week 120
Secondary	Change from baseline in ETDRS-DRSS score over time		Baseline up to Week 120
Secondary	Change from baseline in CST as measured on SD-OCT over time		Baseline up to Week 120
Secondary	Change from baseline in total macular volume as measured on SD-OCT over time		Baseline up to Week 120
Secondary	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
Secondary	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
Secondary	Percentage of participants with absence of intraretinal fluid and subretinal fluid over time		Baseline up to Week 120
Secondary	Percentage of participants with absence DME (defined as CST =325 µm on SD-OCT) over time	DME = diabetic macular edema	Baseline up to Week 120
Secondary	Time to PDR (defined as a score =60 on the ETDRS-DRSS)	PDR = proliferative diabetic retinopathy	Baseline up to Week 120
Secondary	Percentage of participants who do not undergo supplemental treatment with intravitreal ranibizumab within each refill-exchange interval		Baseline up to Week 120
Secondary	Percentage of participants who report preferring PDS treatment compared with intravitreal ranibizumab treatment	As measured by the PDS Patient Preference Questionnaire at Week 64 among patients in the PDS arm efficacy population, mITT population	Baseline to Week 64
Secondary	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	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	Baseline to Week 64
Secondary	Patient-reported vision-related functioning and health-related quality of life (HRQoL) among patients in both treatment arms, as measured by changes from baseline	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	, Baseline Week 48, Week 96
Secondary	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
Secondary	Incidence and severity of ocular adverse events		Baseline to Week 120
Secondary	Incidence and severity of non-ocular adverse events		Baseline up to Week 120
Secondary	Incidence, severity, and duration of adverse events of special interest		Baseline up to Week 120
Secondary	Serum concentration of ranibizumab observed over time		Baseline up to Week 120
Secondary	PK parameter value area under the concentration- time curve over 24 weeks (AUC24W)		Baseline to Week 24
Secondary	Pharmacokinetic (PK) parameter maximum serum concentration (Cmax)		Baseline up to Week 120
Secondary	PK Parameter minimum serum concentration (Cmin)		Baseline up to Week 120
Secondary	Time of maximum observed serum concentration (Tmax) after PDS implant insertion		Baseline up to Week 120
Secondary	Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study		Baseline up to Week 120
Secondary	Prevalence of neutralizing antibodies at baseline and incidence of neutralizing antibodies during the study		Baseline up to Week 120
Secondary	Reported incidence of device deficiencies		Baseline up to Week 120
Secondary	Incidence and severity of ocular adverse events		Baseline up to Week 120
Secondary	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
Secondary	Incidence and severity of adverse device effects		Baseline up to Week 120
Secondary	Incidence, causality, severity, and duration of anticipated serious adverse device effects		Baseline up to Week 120