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

Overview

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

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: January 18, 2023

Interventions

  • 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.

Arms, Groups and Cohorts

  • 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
  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS at Week 52
    • Time Frame: 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.

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Hoffmann-La Roche
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Clinical Trials, Study Director, Hoffmann-La Roche
  • Overall Contact(s)
    • Reference Study ID Number: GR41675 www.roche.com/about_roche/roche_worldwide.htm, 888-662-6728 (U.S., global.rochegenentechtrials@roche.com

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.