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 (Pagoda)

• ClinicalTrials.gov Identifier: NCT04108156
• Recruitment Status: Recruiting
• First Posted: September 30, 2019
• Last Update Posted: December 17, 2020
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: September 26, 2019
• First Posted Date: September 30, 2019
• Last Update Posted Date: December 17, 2020
• Actual Study Start Date: September 30, 2019
• Estimated Primary Completion Date: October 25, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 15, 2020)

Change in BCVA score from baseline averaged over Weeks 60 and 64 as measured using the ETDRS chart in the efficacy population [ Time Frame: Baseline to Week 64 ]

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.

Original Primary Outcome Measures (submitted: September 26, 2019)

Change in BCVA score from baseline averaged over Weeks 48 and 52 as measured using the ETDRS chart [ Time Frame: Baseline to Week 52 ]

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.

Current Secondary Outcome Measures (submitted: December 15, 2020)

• Change in BCVA score from baseline averaged over Weeks 60 and 64 as measured with use of the ETDRS chart in the per protocol population [ Time Frame: Baseline to Week 64 ]
  ETDRS-DRSS = ETDRS Diabetic Retinopathy Severity Scale
• Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS at Week 64 in the efficacy population [ Time Frame: Baseline to Week 64 ]
• Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS at Week 64 in the per protocol population [ Time Frame: Baseline to Week 64 ]
• Change from baseline in BCVA as measured on the ETDRS chart over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants who lose <10, and <5 letters in BCVA from baseline over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants who gain ≥15, ≥10, ≥5, ≥0 letters in BCVA from baseline over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants with a BCVA Snellen equivalent of 20/40 or better over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants with a BCVA Snellen equivalent of 20/200 or worse over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants with a ≥3-step improvement from baseline on the ETDRS-DRSS at Week 64 [ Time Frame: Baseline to Week 64 ]
• Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants with a ≥3-step improvement from baseline on the ETDRS-DRSS over time [ Time Frame: Baseline up to Week 120 ]
• Time to ≥2-step worsening from baseline on the ETDRS-DRSS [ Time Frame: Baseline up to Week 120 ]
• Time to ≥3-step worsening from baseline on the ETDRS-DRSS [ Time Frame: Baseline up to Week 120 ]
• Change from baseline in ETDRS-DRSS score over time [ Time Frame: Baseline up to Week 120 ]
• Change from baseline in CST as measured on SD-OCT at Week 64 [ Time Frame: Baseline to Week 64 ]
  CST = central subfield thickness SD-OCT = spectral domain optical coherence tomography
• Change from baseline in CST as measured on SD-OCT over time [ Time Frame: Baseline up to Week 120 ]
• Change from baseline in total macular volume as measured on SD-OCT over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants with DME (defined as CST ≥325 μm on SD-OCT) over time [ Time Frame: Baseline up to Week 120 ]
  DME = diabetic macular edema
• Time to PDR (defined as a score ≥60 on the ETDRS-DRSS) [ Time Frame: Baseline up to Week 120 ]
  PDR = proliferative diabetic retinopathy
• Percentage of participants who do not undergo supplemental treatment with intravitreal ranibizumab within each refill-exchange interval [ Time Frame: Baseline up to Week 120 ]
• 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 among participants in the PDS arm efficacy population [ Time Frame: Baseline to Week 64 ]
• 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 among participants in per protocol population [ Time Frame: Baseline to Week 64 ]
• 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 [ Time Frame: Baseline to 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
• Incidence and severity of ocular adverse events [ Time Frame: Baseline to Week 120 ]
• Incidence and severity of non-ocular adverse events [ Time Frame: Baseline up to Week 120 ]
• Incidence, severity, and duration of adverse events of special interest [ Time Frame: Baseline up to Week 120 ]
• Incidence, severity, and duration of PDS-associated 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) [ Time Frame: Baseline up to Week 120 ]
• Serum concentration of ranibizumab observed over time [ Time Frame: Baseline up to Week 120 ]
• PK parameter value area under the concentration- time curve over 24 weeks (AUC24W) [ Time Frame: Baseline to Week 24 ]
• Pharmacokinetic (PK) parameter maximum serum concentration (Cmax) [ Time Frame: Baseline up to Week 120 ]
• PK Parameter minimum serum concentration (Cmin) [ Time Frame: Baseline up to Week 120 ]
• PK parameter half-life (t1/2) after PDS implant insertion [ Time Frame: Baseline up to Week 120 ]
• Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study [ Time Frame: Baseline up to Week 120 ]

Original Secondary Outcome Measures (submitted: September 26, 2019)

• Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS at Week 52 [ Time Frame: Baseline to Week 52 ]
  ETDRS-DRSS = ETDRS Diabetic Retinopathy Severity Scale
• Change from baseline in BCVA as measured on the ETDRS chart over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants who lose <15, <10, and <5 letters in BCVA from baseline over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants who gain ≥15, ≥10, ≥5, ≥0 letters in BCVA from baseline over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants with a BCVA Snellen equivalent of 20/40 or better over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants with a BCVA Snellen equivalent of 20/200 or worse over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants with a ≥3-step improvement from baseline on the ETDRS-DRSS at Week 52 [ Time Frame: Baseline to Week 52 ]
• Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants with a ≥3-step improvement from baseline on the ETDRS-DRSS over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants with a ≥2-step worsening from baseline on the ETDRS-DRSS over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants with a ≥3-step worsening from baseline on the ETDRS-DRSS over time [ Time Frame: Baseline up to Week 120 ]
• Change from baseline in ETDRS-DRSS score over time [ Time Frame: Baseline up to Week 120 ]
• Change from baseline in CST as measured on SD-OCT at Week 52 [ Time Frame: Baseline to Week 52 ]
  CST = central subfield thickness SD-OCT = spectral domain optical coherence tomography
• Change from baseline in CST as measured on SD-OCT over time [ Time Frame: Baseline up to Week 120 ]
• Change from baseline in total macular volume as measured on SD-OCT over time [ Time Frame: Baseline up to Week 120 ]
• Percentage of participants with DME (defined as CST ≥325 μm on SD-OCT) over time [ Time Frame: Baseline up to Week 120 ]
  DME = diabetic macular edema
• Percentage of participants with PDR (defined as a score ≥60 on the ETDRS-DRSS) over time [ Time Frame: Baseline up to Week 120 ]
  PDR = proliferative diabetic retinopathy
• Incidence and severity of ocular adverse events [ Time Frame: Baseline to Week 120 ]
• Incidence and severity of non-ocular adverse events [ Time Frame: Baseline up to Week 120 ]
• Incidence, severity, and duration of adverse events of special interest [ Time Frame: Baseline up to Week 120 ]
• Incidence, severity, and duration of PDS-associated 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) [ Time Frame: Baseline up to Week 120 ]
• Serum concentration of ranibizumab observed over time [ Time Frame: Baseline up to Week 120 ]
• PK parameter value area under the concentration- time curve over 24 weeks (AUC24W) [ Time Frame: Baseline to Week 24 ]
• Pharmacokinetic (PK) parameter maximum serum concentration (Cmax) [ Time Frame: Baseline up to Week 120 ]
• PK Parameter minimum serum concentration (Cmin) [ Time Frame: Baseline up to Week 120 ]
• PK parameter half-life (t1/2) after PDS implant insertion [ Time Frame: Baseline up to Week 120 ]
• Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study [ Time Frame: Baseline up to Week 120 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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)
• Brief 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Diabetic Macular Edema

Intervention

• 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.

Study Arms

• Experimental: PDS Arm
  Participants randomized to the PDS arm will receive intravitreal ranibizumab injection every 4 weeks (loading phase) 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 24-weeks (Q24W) thereafter
  Intervention: Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab
• Active Comparator: Intravitreal Arm
  Participants randomized to the intravitreal arm will receive intravitreal ranibizumab injection every 4 weeks until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q24W thereafter.
  Intervention: Drug: Intravitreal Ranibizumab 0.5 mg Injection

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 26, 2019): 545
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 10, 2024
• Estimated Primary Completion Date: October 25, 2022 (Final data collection date for primary outcome measure)

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 ≤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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: GR40550 www.roche.com/about_roche/roche_worldwide.htm; 888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04108156
• Other Study ID Numbers: GR40550
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Responsible Party: Hoffmann-La Roche
• Study Sponsor: Hoffmann-La Roche
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: December 2020