Study of the Efficacy and Safety of the Ranibizumab Port Delivery System for Sustained Delivery of Ranibizumab in Patients With Subfoveal Neovascular Age-Related Macular Degeneration
- Registration Number
- NCT02510794
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This is a Phase II multicenter, dose-ranging, randomized, active treatment (monthly ITV injection)-controlled study to evaluate the efficacy, safety, and pharmacokinetics of ranibizumab delivered through the Implant using three ranibizumab formulation arms (10 mg/mL, 40 mg/mL, and 100 mg/mL) compared with the control arm (0.5-mg monthly ITV injections of 10-mg/mL formulation) in participants with subfoveal neovascular age-related macular degeneration (nAMD).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 225
- Newly diagnosed with wet AMD within 9 months of screening visit
- Participant must have received at least 2 prior ITV anti-vascular endothelial growth factor (VEGF) injections. However, the most recent anti-VEGF injection must have been ranibizumab and must have occurred at least 7 days prior to the screening visit
- Demonstrated response to prior ITV anti-VEGF treatment
- Best Corrected Visual Acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) charts of 20/20-20/200 Snellen equivalent
- Treatment with ITV anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit in either eye
- Study eye treatment with ITV anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit
- History of laser photocoagulation, Visudyne®, ITV corticosteroid injection, vitrectomy surgery, submacular surgery, device implantation, or other surgical intervention for AMD in the study eye
- Prior participation in a clinical trial involving anti-angiogenic drugs, other than ranibizumab, in either eye within 2 months of the randomization visit
- Subretinal hemorrhage in the study eye that involves the center of the fovea
- Subfoveal fibrosis, or atrophy in the study eye
- Choroidal neovascularization (CNV) in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
- Uncontrolled ocular hypertension or glaucoma in the study eye
- History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery in the study eye
- Uncontrolled blood pressure
- Uncontrolled atrial fibrillation within 3 months of informed consent
- History of myocardial infarction or stroke within the last 3 months prior to informed consent
- History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the Implant, that might affect interpretation of the results of the study or renders the participant at high risk of treatment complications
- Use of oral corticosteroids
- Current treatment for any active systemic infection
- Use of anticoagulants, anti-platelets (other than aspirin), or medications known to exert similar effects
- Active malignancy within 12 months of randomization
- History of allergy to fluorescein
- Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent (excluding vitamins and minerals)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Port Delivery System with Ranibizumab 10mg/mL Ranibizumab Participants had the Implant (prefilled with approximately 20 μL of 10-mg/mL ,approximately 0.2 mg dose, of ranibizumab) surgically inserted in the study eye at the Day 1 visit following their randomization visit. Starting at the Month 1 visit, participants were evaluated monthly for the need for Implant refill with the 10-mg/mL formulation of ranibizumab according to their randomization as per protocol-specified refill criteria. Port Delivery System with Ranibizumab 40mg/mL Ranibizumab Participants had the Implant (prefilled with approximately 20 μL of 40-mg/mL, approximately 0.8 mg dose, of ranibizumab) surgically inserted in the study eye at the Day 1 visit following their randomization visit. Starting at the Month 1 visit, participants were evaluated monthly for the need for Implant refill with the 40-mg/mL formulation of ranibizumab according to their randomization as per protocol-specified refill criteria. Port Delivery System with Ranibizumab 100mg/mL Ranibizumab Participants had the Implant (prefilled with approximately 20 μL of 100-mg/mL, approximately 2 mg dose, of ranibizumab) surgically inserted in the study eye at the Day 1 visit following their randomization visit. Starting at the Month 1 visit, participants were evaluated monthly for the need for Implant refill with the 100-mg/mL formulation of ranibizumab according to their randomization as per protocol-specified refill criteria. Intravitreal Injection with Ranibizumab 0.5mg Ranibizumab Participants received ranibizumab 0.5 mg monthly ITV injections of 10 mg/mL formulation at Day 1 and every month thereafter.
- Primary Outcome Measures
Name Time Method Time Until a Participant First Requires the Implant Refill According to Protocol-Defined Refill Criteria Baseline up to approximately 38 months Protocol-Defined Refill Criteria
At 1 month after initial fill:
* Decrease of ≥ 10 letters in BCVA at the current visit compared with the baseline BCVA, due to nAMD disease activity OR
* Increase in CFT of ≥ 100 um at the current visit compared with the baseline CFT, due to nAMD disease activity OR
* Presence of new macular hemorrhage, due to nAMD disease activity
For subsequent assessments:
* Increase in CFT of ≥ 75 μm on SD-OCT at the current visit compared with the average CFT over the last 2 available measurements, due to nAMD disease activity OR
* Increase in CFT of ≥ 100 um from the lowest CFT measurement on study, due to nAMD disease activity OR
* Decrease of ≥ 5 letters in BCVA at the current visit compared with the average BCVA over the last 2 available measurements, due to nAMD disease activity OR
* Decrease of ≥ 10 letters from best recorded BCVA on study, due to nAMD disease activity OR
* Presence of new macular hemorrhage, due to nAMD disease activity
- Secondary Outcome Measures
Name Time Method Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged At Month 9 and 10 Baseline, Months 9, 10 Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. The minimum score possible is 0 and maximum possible is 100. A higher score represents better functioning.
Number of Implant Clogging at Month 9 Month 9 Removed implants identified as meeting serum PK criteria for possible clogging were assessed via lab-based investigation (in vitro drug release testing) to determine whether there was any implant clogging.
Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) Baseline up to Month 9 Central foveal thickness (CFT) is defined as the retinal thickness in the center of the fovea
Observed Steady-State Serum Concentration at the End of a Dosing Interval (Ctrough) of Ranibizumab Predose (0 hour) on Day 1 up to 38 months Time to Maximum Concentration (Tmax) of Ranibizumab Predose (0 hour) on Day 1 up to 38 months The serum pharmacokinetics of ranibizumab were characterized by estimating Tmax between dose intervals. Estimates for these parameters were tabulated and summarized by descriptive statistics.
Change From Baseline in BCVA Over Time Baseline up to Month 10 Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. The minimum score possible is 0 and maximum possible is 100. A higher score represents better functioning.
Adjusted Average Change From Baseline in BCVA Over Time (MMRM Analysis) Baseline up to Month 10 Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. The minimum score possible is 0 and maximum possible is 100. A higher score represents better functioning. Here, the adjusted mean from MMRM analysis is presented).
Observed Maximum Serum Concentration (Cmax) of Ranibizumab Predose (0 hour) on Day 1 up to 38 months The serum pharmacokinetics of ranibizumab were characterized by estimating Cmax between dose intervals. Estimates for these parameters were tabulated and summarized by descriptive statistics.
Area Under the Concentration-Time Curve From Dosing to Last Observation (AUClast) of Ranibizumab Predose (0 hour) on Day 1 up to approximately 38 months (detailed timeframe is provided in description field) AUCLast is defined as area under the concentration-time curve from dosing (implant or refill) to last observation before next refill or exiting the study. The serum pharmacokinetics of ranibizumab were characterized by estimating AUC between dose intervals. Estimates for these parameters were tabulated and summarized by descriptive statistics.
Terminal Half-Life (t1/2) of Ranibizumab Predose (0 hour) on Day 1 up to 38 months The serum pharmacokinetics of ranibizumab were characterized by estimating t1/2 between dose intervals. Estimates for these parameters were tabulated and summarized by descriptive statistics.
Percentage of Participants With Positive Serum Antibodies to Ranibizumab Baseline up to 38 months Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) Baseline up to approximately Month 38
Trial Locations
- Locations (50)
Barnet Dulaney Perkins Eye Center
🇺🇸Mesa, Arizona, United States
Retinal Research Institute, LLC
🇺🇸Phoenix, Arizona, United States
Associated Retina Consultants
🇺🇸Phoenix, Arizona, United States
The Retina Partners
🇺🇸Encino, California, United States
Jacobs Retina center at the Shiley eye Institute UCSD
🇺🇸La Jolla, California, United States
Jules Stein Eye Institute/ UCLA
🇺🇸Los Angeles, California, United States
N CA Retina Vitreous Assoc
🇺🇸Mountain View, California, United States
Retinal Consultants Med Group
🇺🇸Sacramento, California, United States
West Coast Retina Medical Group
🇺🇸San Francisco, California, United States
UCSF; Ophthalmology
🇺🇸San Francisco, California, United States
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