Macular Degeneration
Conditions
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).
Interventions
DRUGRanibizumab
Ranibizumab will be administered at dose of 0.5 mg monthly ITV injections of 10-mg/mL formulation or delivered through the implant with three different formulations.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 | — |
| Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Baseline up to approximately Month 38 | — |
| Percentage of Participants With Positive Serum Antibodies to Ranibizumab | Baseline up to 38 months | — |
| 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. |
Countries
United States
Participant flow
Recruitment details
Participants with subfoveal neovascularization secondary to AMD diagnosed within 9 months and treated with ITV anti-VEGF agents were enrolled in the study. Written informed consent was obtained before initiation of any study-related procedures. A participant's screening occurred no sooner than 7 days following administration of the last ITV ranibizumab treatment to the study eye. The screening visit was followed by the randomization visit.
Participants by arm
| Arm | Count |
|---|---|
| Port Delivery System With Ranibizumab 10mg/mL 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. | 59 |
| Port Delivery System With Ranibizumab 40mg/mL 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. | 62 |
| Port Delivery System With Ranibizumab 100mg/mL 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. | 63 |
| Intravitreal Injection With Ranibizumab 0.5mg Participants received ranibizumab 0.5 mg monthly ITV injections of 10 mg/mL formulation at Day 1 and every month thereafter. | 41 |
| Total | 225 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 |
| Overall Study | Death | 1 | 2 | 1 | 1 |
| Overall Study | Lack of Efficacy | 3 | 1 | 1 | 0 |
| Overall Study | Participant moved out of the area | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 3 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 4 | 3 |
Baseline characteristics
| Characteristic | Port Delivery System With Ranibizumab 10mg/mL | Port Delivery System With Ranibizumab 40mg/mL | Port Delivery System With Ranibizumab 100mg/mL | Intravitreal Injection With Ranibizumab 0.5mg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 51 Participants | 55 Participants | 54 Participants | 34 Participants | 194 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 7 Participants | 9 Participants | 7 Participants | 31 Participants |
| Age, Continuous | 74.6 Years STANDARD_DEVIATION 8.4 | 75.0 Years STANDARD_DEVIATION 8.5 | 73.8 Years STANDARD_DEVIATION 8.1 | 71.9 Years STANDARD_DEVIATION 8.8 | 74.0 Years STANDARD_DEVIATION 8.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 56 Participants | 60 Participants | 39 Participants | 211 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 58 Participants | 61 Participants | 60 Participants | 41 Participants | 220 Participants |
| Sex: Female, Male Female | 37 Participants | 39 Participants | 42 Participants | 28 Participants | 146 Participants |
| Sex: Female, Male Male | 22 Participants | 23 Participants | 21 Participants | 13 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 58 | 2 / 62 | 1 / 59 | 1 / 41 |
| other Total, other adverse events | 57 / 58 | 59 / 62 | 58 / 59 | 35 / 41 |
| serious Total, serious adverse events | 14 / 58 | 19 / 62 | 17 / 59 | 4 / 41 |
Outcome results
Primary
Time Until a Participant First Requires the Implant Refill According to Protocol-Defined Refill Criteria
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
Time frame: Baseline up to approximately 38 months
Population: Efficacy Population defined as all participants who were randomly assigned to study treatment and received at least one study treatment, excluding 5 participants who were given surgery.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Port Delivery System With Ranibizumab 10mg/mL | Time Until a Participant First Requires the Implant Refill According to Protocol-Defined Refill Criteria | 8.7 Months |
| Port Delivery System With Ranibizumab 40mg/mL | Time Until a Participant First Requires the Implant Refill According to Protocol-Defined Refill Criteria | 13.0 Months |
| Port Delivery System With Ranibizumab 100mg/mL | Time Until a Participant First Requires the Implant Refill According to Protocol-Defined Refill Criteria | 15.8 Months |
Secondary
Adjusted Average Change From Baseline in BCVA Over Time (MMRM Analysis)
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).
Time frame: Baseline up to Month 10
Population: Efficacy Population defined as all participants who were randomly assigned to study treatment and received at least one study treatment. Assessments are censored for PDS participants meeting the following situations:~* At the time of an ITV anti-VEGF injection in study eye prior to Month 10.~* Prohibited therapy other than oral corticosteroids more than 10 mg/day or any fellow eye treatment.~* At the time of explant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Port Delivery System With Ranibizumab 10mg/mL | Adjusted Average Change From Baseline in BCVA Over Time (MMRM Analysis) | -7.5 Units on scale | Standard Deviation 74 |
| Port Delivery System With Ranibizumab 40mg/mL | Adjusted Average Change From Baseline in BCVA Over Time (MMRM Analysis) | -8.5 Units on scale | Standard Deviation 59.1 |
| Port Delivery System With Ranibizumab 100mg/mL | Adjusted Average Change From Baseline in BCVA Over Time (MMRM Analysis) | 29.7 Units on scale | Standard Deviation 54.7 |
| Intravitreal Injection With Ranibizumab 0.5mg | Adjusted Average Change From Baseline in BCVA Over Time (MMRM Analysis) | 21.3 Units on scale | Standard Deviation 65.1 |
Secondary
Area Under the Concentration-Time Curve From Dosing to Last Observation (AUClast) of Ranibizumab
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.
Time frame: Predose (0 hour) on Day 1 up to approximately 38 months (detailed timeframe is provided in description field)
Population: PK Population with exclusion (randomized participants who had received at least one study drug administration and provided at least one serum and/or aqueous PK sample for determination of ranibizumab concentration excluding participants who had prior intravitreal bevacizumab, received fellow eye ranibizumab treatment, and/or received supplemental intravitreal ranibizumab)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Port Delivery System With Ranibizumab 10mg/mL | Area Under the Concentration-Time Curve From Dosing to Last Observation (AUClast) of Ranibizumab | Interval following implant insertion before first refill | 5.89 ng∙day/mL | Geometric Coefficient of Variation 225.1 |
| Port Delivery System With Ranibizumab 10mg/mL | Area Under the Concentration-Time Curve From Dosing to Last Observation (AUClast) of Ranibizumab | All Dose Intervals | 3.43 ng∙day/mL | Geometric Coefficient of Variation 176.8 |
| Port Delivery System With Ranibizumab 40mg/mL | Area Under the Concentration-Time Curve From Dosing to Last Observation (AUClast) of Ranibizumab | Interval following implant insertion before first refill | 28.39 ng∙day/mL | Geometric Coefficient of Variation 107.6 |
| Port Delivery System With Ranibizumab 40mg/mL | Area Under the Concentration-Time Curve From Dosing to Last Observation (AUClast) of Ranibizumab | All Dose Intervals | 22.93 ng∙day/mL | Geometric Coefficient of Variation 96.9 |
| Port Delivery System With Ranibizumab 100mg/mL | Area Under the Concentration-Time Curve From Dosing to Last Observation (AUClast) of Ranibizumab | All Dose Intervals | 66.12 ng∙day/mL | Geometric Coefficient of Variation 71.4 |
| Port Delivery System With Ranibizumab 100mg/mL | Area Under the Concentration-Time Curve From Dosing to Last Observation (AUClast) of Ranibizumab | Interval following implant insertion before first refill | 90.83 ng∙day/mL | Geometric Coefficient of Variation 64.7 |
Secondary
Change From Baseline in BCVA Over Time
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.
Time frame: Baseline up to Month 10
Population: Efficacy Population defined as all participants who were randomly assigned to study treatment and received at least one study treatment. Assessments are censored for PDS participants meeting the following situations:~* At the time of an ITV anti-VEGF injection in study eye prior to Month 10.~* Prohibited therapy other than oral corticosteroids more than 10 mg/day or any fellow eye treatment.~* At the time of explant.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in BCVA Over Time | Month 2 | -2.4 Units on scale |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in BCVA Over Time | Month 8 | -2.4 Units on scale |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in BCVA Over Time | Month 7 | -0.9 Units on scale |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in BCVA Over Time | Month 6 | -0.4 Units on scale |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in BCVA Over Time | Month 9 | -3.3 Units on scale |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in BCVA Over Time | Month 4 | -1.4 Units on scale |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in BCVA Over Time | Month 10 | -3.3 Units on scale |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in BCVA Over Time | Month 3 | -0.7 Units on scale |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in BCVA Over Time | Month 5 | -1.3 Units on scale |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in BCVA Over Time | Month 1 | -6.6 Units on scale |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in BCVA Over Time | Month 5 | -0.6 Units on scale |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in BCVA Over Time | Month 8 | -1.2 Units on scale |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in BCVA Over Time | Month 6 | -1.7 Units on scale |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in BCVA Over Time | Month 7 | -1.8 Units on scale |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in BCVA Over Time | Month 2 | -1.4 Units on scale |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in BCVA Over Time | Month 9 | -0.5 Units on scale |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in BCVA Over Time | Month 3 | -0.6 Units on scale |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in BCVA Over Time | Month 10 | -0.2 Units on scale |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in BCVA Over Time | Month 4 | -1.1 Units on scale |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in BCVA Over Time | Month 1 | -4.7 Units on scale |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in BCVA Over Time | Month 5 | 3.8 Units on scale |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in BCVA Over Time | Month 2 | 1.6 Units on scale |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in BCVA Over Time | Month 7 | 3.9 Units on scale |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in BCVA Over Time | Month 1 | -4.9 Units on scale |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in BCVA Over Time | Month 3 | 2.4 Units on scale |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in BCVA Over Time | Month 4 | 3.1 Units on scale |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in BCVA Over Time | Month 6 | 3.8 Units on scale |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in BCVA Over Time | Month 8 | 4.0 Units on scale |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in BCVA Over Time | Month 9 | 5.0 Units on scale |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in BCVA Over Time | Month 10 | 5.1 Units on scale |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in BCVA Over Time | Month 2 | 2.0 Units on scale |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in BCVA Over Time | Month 8 | 3.3 Units on scale |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in BCVA Over Time | Month 3 | 2.7 Units on scale |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in BCVA Over Time | Month 1 | 2.4 Units on scale |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in BCVA Over Time | Month 10 | 2.5 Units on scale |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in BCVA Over Time | Month 9 | 3.9 Units on scale |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in BCVA Over Time | Month 4 | 1.9 Units on scale |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in BCVA Over Time | Month 7 | 3.5 Units on scale |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in BCVA Over Time | Month 6 | 2.7 Units on scale |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in BCVA Over Time | Month 5 | 3.0 Units on scale |
Secondary
Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged At Month 9 and 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.
Time frame: Baseline, Months 9, 10
Population: Efficacy Population defined as all participants who were randomly assigned to study treatment and received at least one study treatment. Assessments are censored for PDS participants meeting the following situations:~* At the time of an ITV anti-VEGF injection in study eye prior to Month 10.~* Prohibited therapy other than oral corticosteroids more than 10 mg/day or any fellow eye treatment.~* At the time of explant.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged At Month 9 and 10 | -3.3 Units on scale |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged At Month 9 and 10 | -0.3 Units on scale |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged At Month 9 and 10 | 5.0 Units on scale |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged At Month 9 and 10 | 3.2 Units on scale |
Secondary
Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT)
Central foveal thickness (CFT) is defined as the retinal thickness in the center of the fovea
Time frame: Baseline up to Month 9
Population: Efficacy Population defined as all participants who received at least one study treatment. Here, Number of Participants analyzed indicates Number of Participants Included in MMRM Analysis. Assessments are censored for PDS participants meeting the following situations:~* At the time of an ITV anti-VEGF injection in study eye prior to Month 10.~* Prohibited therapy other than oral corticosteroids more than 10 mg/day or any fellow eye treatment.~* At the time of explant.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 5 | 30.9 microns |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 7 | 39.9 microns |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 9 | 54.8 microns |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 8 | 42.8 microns |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 1 | 16.5 microns |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 3 | 24.9 microns |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 6 | 31.9 microns |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 4 | 31.0 microns |
| Port Delivery System With Ranibizumab 10mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 2 | 19.8 microns |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 5 | 0.4 microns |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 6 | 2.1 microns |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 7 | 0.7 microns |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 8 | 3.1 microns |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 2 | 11.9 microns |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 9 | -0.7 microns |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 1 | 7.2 microns |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 3 | 7.3 microns |
| Port Delivery System With Ranibizumab 40mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 4 | 4.1 microns |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 2 | -1.8 microns |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 5 | 8.0 microns |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 3 | 6.4 microns |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 7 | -4.3 microns |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 8 | 5.1 microns |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 6 | 5.9 microns |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 9 | -1.7 microns |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 4 | 1.9 microns |
| Port Delivery System With Ranibizumab 100mg/mL | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 1 | -2.9 microns |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 8 | -2.4 microns |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 2 | 1.5 microns |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 4 | -1.7 microns |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 7 | -9.8 microns |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 9 | -6.3 microns |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 1 | 2.5 microns |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 3 | -7.3 microns |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 5 | 4.0 microns |
| Intravitreal Injection With Ranibizumab 0.5mg | Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Month 6 | -2.0 microns |
Secondary
Number of Implant Clogging at 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.
Time frame: Month 9
Population: Efficacy Population defined as all participants who were randomly assigned to study treatment and received at least one study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Port Delivery System With Ranibizumab 10mg/mL | Number of Implant Clogging at Month 9 | 0 Participants |
| Port Delivery System With Ranibizumab 40mg/mL | Number of Implant Clogging at Month 9 | 0 Participants |
| Port Delivery System With Ranibizumab 100mg/mL | Number of Implant Clogging at Month 9 | 0 Participants |
Secondary
Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs)
Time frame: Baseline up to approximately Month 38
Population: Safety analyses were based on the Safety Population which was composed of participants receiving at least one study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Port Delivery System With Ranibizumab 10mg/mL | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with non-ocular SAEs | 8 Participants |
| Port Delivery System With Ranibizumab 10mg/mL | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with ocular AEs in study eye | 56 Participants |
| Port Delivery System With Ranibizumab 10mg/mL | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with ocular SAEs in study eye | 7 Participants |
| Port Delivery System With Ranibizumab 10mg/mL | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with non-ocular AEs | 46 Participants |
| Port Delivery System With Ranibizumab 40mg/mL | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with ocular AEs in study eye | 58 Participants |
| Port Delivery System With Ranibizumab 40mg/mL | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with ocular SAEs in study eye | 6 Participants |
| Port Delivery System With Ranibizumab 40mg/mL | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with non-ocular SAEs | 16 Participants |
| Port Delivery System With Ranibizumab 40mg/mL | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with non-ocular AEs | 52 Participants |
| Port Delivery System With Ranibizumab 100mg/mL | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with non-ocular SAEs | 13 Participants |
| Port Delivery System With Ranibizumab 100mg/mL | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with ocular SAEs in study eye | 4 Participants |
| Port Delivery System With Ranibizumab 100mg/mL | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with ocular AEs in study eye | 52 Participants |
| Port Delivery System With Ranibizumab 100mg/mL | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with non-ocular AEs | 52 Participants |
| Intravitreal Injection With Ranibizumab 0.5mg | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with ocular AEs in study eye | 166 Participants |
| Intravitreal Injection With Ranibizumab 0.5mg | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with non-ocular AEs | 150 Participants |
| Intravitreal Injection With Ranibizumab 0.5mg | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with non-ocular SAEs | 37 Participants |
| Intravitreal Injection With Ranibizumab 0.5mg | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with ocular SAEs in study eye | 17 Participants |
| Intravitreal Injection With Ranibizumab 0.5mg | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with non-ocular AEs | 36 Participants |
| Intravitreal Injection With Ranibizumab 0.5mg | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with ocular AEs in study eye | 26 Participants |
| Intravitreal Injection With Ranibizumab 0.5mg | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with ocular SAEs in study eye | 0 Participants |
| Intravitreal Injection With Ranibizumab 0.5mg | Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) | Participants with non-ocular SAEs | 4 Participants |
Secondary
Observed Maximum Serum Concentration (Cmax) of Ranibizumab
The serum pharmacokinetics of ranibizumab were characterized by estimating Cmax between dose intervals. Estimates for these parameters were tabulated and summarized by descriptive statistics.
Time frame: Predose (0 hour) on Day 1 up to 38 months
Population: PK Population with exclusion (randomized participants who had received at least one study drug administration and provided at least one serum and/or aqueous PK sample for determination of ranibizumab concentration excluding participants who had prior intravitreal bevacizumab, received fellow eye ranibizumab treatment, and/or received supplemental intravitreal ranibizumab)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Port Delivery System With Ranibizumab 10mg/mL | Observed Maximum Serum Concentration (Cmax) of Ranibizumab | Interval following implant insertion before first refill | 105.52 pg/mL | Geometric Coefficient of Variation 258 |
| Port Delivery System With Ranibizumab 10mg/mL | Observed Maximum Serum Concentration (Cmax) of Ranibizumab | All Dose Intervals | 91.47 pg/mL | Geometric Coefficient of Variation 187.2 |
| Port Delivery System With Ranibizumab 40mg/mL | Observed Maximum Serum Concentration (Cmax) of Ranibizumab | Interval following implant insertion before first refill | 220.87 pg/mL | Geometric Coefficient of Variation 46.4 |
| Port Delivery System With Ranibizumab 40mg/mL | Observed Maximum Serum Concentration (Cmax) of Ranibizumab | All Dose Intervals | 297.61 pg/mL | Geometric Coefficient of Variation 115.2 |
| Port Delivery System With Ranibizumab 100mg/mL | Observed Maximum Serum Concentration (Cmax) of Ranibizumab | Interval following implant insertion before first refill | 1080.69 pg/mL | Geometric Coefficient of Variation 272.5 |
| Port Delivery System With Ranibizumab 100mg/mL | Observed Maximum Serum Concentration (Cmax) of Ranibizumab | All Dose Intervals | 1131.01 pg/mL | Geometric Coefficient of Variation 256.6 |
Secondary
Observed Steady-State Serum Concentration at the End of a Dosing Interval (Ctrough) of Ranibizumab
Time frame: Predose (0 hour) on Day 1 up to 38 months
Population: PK Population with exclusion (randomized participants who had received at least one study drug administration and provided at least one serum and/or aqueous PK sample for determination of ranibizumab concentration excluding participants who had prior intravitreal bevacizumab, received fellow eye ranibizumab treatment, and/or received supplemental intravitreal ranibizumab)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Port Delivery System With Ranibizumab 10mg/mL | Observed Steady-State Serum Concentration at the End of a Dosing Interval (Ctrough) of Ranibizumab | Interval following implant insertion before first refill | 14.96 pg/mL | Geometric Coefficient of Variation 76.4 |
| Port Delivery System With Ranibizumab 10mg/mL | Observed Steady-State Serum Concentration at the End of a Dosing Interval (Ctrough) of Ranibizumab | All Dose Intervals | 11.58 pg/mL | Geometric Coefficient of Variation 65.7 |
| Port Delivery System With Ranibizumab 40mg/mL | Observed Steady-State Serum Concentration at the End of a Dosing Interval (Ctrough) of Ranibizumab | Interval following implant insertion before first refill | 61.64 pg/mL | Geometric Coefficient of Variation 95.8 |
| Port Delivery System With Ranibizumab 40mg/mL | Observed Steady-State Serum Concentration at the End of a Dosing Interval (Ctrough) of Ranibizumab | All Dose Intervals | 105.07 pg/mL | Geometric Coefficient of Variation 77.4 |
| Port Delivery System With Ranibizumab 100mg/mL | Observed Steady-State Serum Concentration at the End of a Dosing Interval (Ctrough) of Ranibizumab | Interval following implant insertion before first refill | 129.63 pg/mL | Geometric Coefficient of Variation 149.2 |
| Port Delivery System With Ranibizumab 100mg/mL | Observed Steady-State Serum Concentration at the End of a Dosing Interval (Ctrough) of Ranibizumab | All Dose Intervals | 62.19 pg/mL | Geometric Coefficient of Variation 345.2 |
Secondary
Percentage of Participants With Positive Serum Antibodies to Ranibizumab
Time frame: Baseline up to 38 months
Population: Safety analyses were based on the Safety Population which was composed of participants receiving at least one study treatment. Here, number of analyzed participants represents number of participants from whom samples were collected and analyzed. Baseline evaluable participant is a participant with an ADA assay result from a baseline sample(s). Post-baseline evaluable participant is a participant with an ADA assay result from at least one post-baseline sample.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Port Delivery System With Ranibizumab 10mg/mL | Percentage of Participants With Positive Serum Antibodies to Ranibizumab | Participants with a positive sample at time of entry into the study (Baseline) | 10.3 Percentage of Participants |
| Port Delivery System With Ranibizumab 10mg/mL | Percentage of Participants With Positive Serum Antibodies to Ranibizumab | Participants positive for Treatment Emergent ADA (Post-baseline) | 6.9 Percentage of Participants |
| Port Delivery System With Ranibizumab 40mg/mL | Percentage of Participants With Positive Serum Antibodies to Ranibizumab | Participants with a positive sample at time of entry into the study (Baseline) | 5.0 Percentage of Participants |
| Port Delivery System With Ranibizumab 40mg/mL | Percentage of Participants With Positive Serum Antibodies to Ranibizumab | Participants positive for Treatment Emergent ADA (Post-baseline) | 14.5 Percentage of Participants |
| Port Delivery System With Ranibizumab 100mg/mL | Percentage of Participants With Positive Serum Antibodies to Ranibizumab | Participants with a positive sample at time of entry into the study (Baseline) | 5.1 Percentage of Participants |
| Port Delivery System With Ranibizumab 100mg/mL | Percentage of Participants With Positive Serum Antibodies to Ranibizumab | Participants positive for Treatment Emergent ADA (Post-baseline) | 15.3 Percentage of Participants |
| Intravitreal Injection With Ranibizumab 0.5mg | Percentage of Participants With Positive Serum Antibodies to Ranibizumab | Participants positive for Treatment Emergent ADA (Post-baseline) | 12.3 Percentage of Participants |
| Intravitreal Injection With Ranibizumab 0.5mg | Percentage of Participants With Positive Serum Antibodies to Ranibizumab | Participants with a positive sample at time of entry into the study (Baseline) | 6.8 Percentage of Participants |
| Intravitreal Injection With Ranibizumab 0.5mg | Percentage of Participants With Positive Serum Antibodies to Ranibizumab | Participants with a positive sample at time of entry into the study (Baseline) | 0 Percentage of Participants |
| Intravitreal Injection With Ranibizumab 0.5mg | Percentage of Participants With Positive Serum Antibodies to Ranibizumab | Participants positive for Treatment Emergent ADA (Post-baseline) | 14.6 Percentage of Participants |
Secondary
Terminal Half-Life (t1/2) of Ranibizumab
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.
Time frame: Predose (0 hour) on Day 1 up to 38 months
Population: PK Population with exclusion (randomized participants who had received at least one study drug administration and provided at least one serum and/or aqueous PK sample for determination of ranibizumab concentration excluding participants who had prior intravitreal bevacizumab, received fellow eye ranibizumab treatment, and/or received supplemental intravitreal ranibizumab)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Port Delivery System With Ranibizumab 10mg/mL | Terminal Half-Life (t1/2) of Ranibizumab | Interval following implant insertion before first refill | 168.20 days | Geometric Coefficient of Variation 163.3 |
| Port Delivery System With Ranibizumab 10mg/mL | Terminal Half-Life (t1/2) of Ranibizumab | All Dose Intervals | 162.36 days | Geometric Coefficient of Variation 129.3 |
| Port Delivery System With Ranibizumab 40mg/mL | Terminal Half-Life (t1/2) of Ranibizumab | Interval following implant insertion before first refill | 88.30 days | Geometric Coefficient of Variation 46.7 |
| Port Delivery System With Ranibizumab 40mg/mL | Terminal Half-Life (t1/2) of Ranibizumab | All Dose Intervals | 118.87 days | Geometric Coefficient of Variation 76.2 |
| Port Delivery System With Ranibizumab 100mg/mL | Terminal Half-Life (t1/2) of Ranibizumab | All Dose Intervals | 143.87 days | Geometric Coefficient of Variation 171.4 |
| Port Delivery System With Ranibizumab 100mg/mL | Terminal Half-Life (t1/2) of Ranibizumab | Interval following implant insertion before first refill | 119.07 days | Geometric Coefficient of Variation 128.4 |
Secondary
Time to Maximum Concentration (Tmax) of Ranibizumab
The serum pharmacokinetics of ranibizumab were characterized by estimating Tmax between dose intervals. Estimates for these parameters were tabulated and summarized by descriptive statistics.
Time frame: Predose (0 hour) on Day 1 up to 38 months
Population: PK Population with exclusion (randomized participants who had received at least one study drug administration and provided at least one serum and/or aqueous PK sample for determination of ranibizumab concentration excluding participants who had prior intravitreal bevacizumab, received fellow eye ranibizumab treatment, and/or received supplemental intravitreal ranibizumab)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Port Delivery System With Ranibizumab 10mg/mL | Time to Maximum Concentration (Tmax) of Ranibizumab | Interval following implant insertion before first refill | 11.45 days |
| Port Delivery System With Ranibizumab 10mg/mL | Time to Maximum Concentration (Tmax) of Ranibizumab | All Dose Intervals | 4.87 days |
| Port Delivery System With Ranibizumab 40mg/mL | Time to Maximum Concentration (Tmax) of Ranibizumab | Interval following implant insertion before first refill | 12.87 days |
| Port Delivery System With Ranibizumab 40mg/mL | Time to Maximum Concentration (Tmax) of Ranibizumab | All Dose Intervals | 6.71 days |
| Port Delivery System With Ranibizumab 100mg/mL | Time to Maximum Concentration (Tmax) of Ranibizumab | Interval following implant insertion before first refill | 29.01 days |
| Port Delivery System With Ranibizumab 100mg/mL | Time to Maximum Concentration (Tmax) of Ranibizumab | All Dose Intervals | 6.97 days |