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)

Roche

Status and phase: Active, not recruiting; Phase 3

Conditions: Diabetic Retinopathy

Treatments: Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab; Drug: Intravitreal Ranibizumab 0.5 mg Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT04503551

GR41675

Details and patient eligibility

About

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

Enrollment: 174 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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174 participants in 2 patient groups

PDS Arm

Experimental group

Description:

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

Treatment:

Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab

Drug: Intravitreal Ranibizumab 0.5 mg Injection

Comparator Arm

Other group

Description:

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.

Treatment:

Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab

Drug: Intravitreal Ranibizumab 0.5 mg Injection