Trial Outcomes & Findings for 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 (NCT NCT04503551)

NCT ID: NCT04503551

Last Updated: 2025-11-25

Results Overview

ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy. The Cochran-Mantel Haenszel (CMH) method was used for analysis and weighted percentage of participants are estimated and reported in this outcome measure. Participants receiving supplemental treatments, prohibited therapy, or panretinal photocoagulation (PRP) were considered non-responders. Missing values not preceded by these intercurrent events were imputed using the last observation carried forward method. SD OCT= spectral-domain optical coherence tomography.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE3
• Target enrollment: 174 participants
• Primary outcome timeframe: Baseline, Week 52
• Results posted on: 2025-11-25

Participant Flow

Participants were enrolled in this study at 50 investigative sites in the United States from 10 August 2020. The study is ongoing. The analyses presented in this results summary are based on a primary completion date (clinical cut-off) of 03 October 2022.

A total of 174 participants with moderately severe or severe non-proliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) were randomized in a 5:3 ratio to either port delivery system (PDS) arm or comparator arm.

Participant milestones

Measure	PDS With Ranibizumab 100 mg/mL Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm Participants underwent study visits every 4 weeks (Q4W) for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Overall Study STARTED	106	68
Overall Study Safety Evaluable Population	105	68
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	106	68

Reasons for withdrawal

Measure	PDS With Ranibizumab 100 mg/mL Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm Participants underwent study visits every 4 weeks (Q4W) for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Overall Study Withdrawal by Subject	5	3
Overall Study Physician Decision	1	0
Overall Study Death	0	1
Overall Study Lost to Follow-up	1	2
Overall Study Ongoing at Week 52	99	62

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	PDS With Ranibizumab 100 mg/mL n=106 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm n=68 Participants Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Total n=174 Participants Total of all reporting groups
Age, Continuous	53.7 years STANDARD_DEVIATION 11.32 • n=45 Participants	54.1 years STANDARD_DEVIATION 12.30 • n=12929 Participants	53.9 years STANDARD_DEVIATION 11.68 • n=6349 Participants
Sex: Female, Male Female	47 Participants n=45 Participants	27 Participants n=12929 Participants	74 Participants n=6349 Participants
Sex: Female, Male Male	59 Participants n=45 Participants	41 Participants n=12929 Participants	100 Participants n=6349 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	43 Participants n=45 Participants	29 Participants n=12929 Participants	72 Participants n=6349 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	63 Participants n=45 Participants	39 Participants n=12929 Participants	102 Participants n=6349 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=45 Participants	0 Participants n=12929 Participants	0 Participants n=6349 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=45 Participants	0 Participants n=12929 Participants	4 Participants n=6349 Participants
Race (NIH/OMB) Asian	9 Participants n=45 Participants	8 Participants n=12929 Participants	17 Participants n=6349 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=45 Participants	0 Participants n=12929 Participants	2 Participants n=6349 Participants
Race (NIH/OMB) Black or African American	14 Participants n=45 Participants	4 Participants n=12929 Participants	18 Participants n=6349 Participants
Race (NIH/OMB) White	73 Participants n=45 Participants	52 Participants n=12929 Participants	125 Participants n=6349 Participants
Race (NIH/OMB) More than one race	0 Participants n=45 Participants	0 Participants n=12929 Participants	0 Participants n=6349 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=45 Participants	4 Participants n=12929 Participants	8 Participants n=6349 Participants

PRIMARY outcome

Timeframe: Baseline, Week 52

Population: ITT Population included all participants who were randomized. Participants were grouped according to treatment assigned at randomization.

ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy. The Cochran-Mantel Haenszel (CMH) method was used for analysis and weighted percentage of participants are estimated and reported in this outcome measure. Participants receiving supplemental treatments, prohibited therapy, or panretinal photocoagulation (PRP) were considered non-responders. Missing values not preceded by these intercurrent events were imputed using the last observation carried forward method. SD OCT= spectral-domain optical coherence tomography.

Outcome measures

Measure	PDS With Ranibizumab 100 mg/mL n=106 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm n=68 Participants Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Percentage of Participants With a ≥2-Step Improvement From Baseline on the Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale (ETDRS-DRSS) at Week 52	80.1 percentage of participants	9.0 percentage of participants

SECONDARY outcome

Timeframe: From Baseline through Week 52

Population: ITT Population included all participants who were randomized. Participants were grouped according to treatment assigned at randomization.

A vision threatening complication is defined as proliferative DR (PDR) or anterior segment neovascularization (ASNV) or center-involved diabetic macular edema (CI-DME). CI-DME is defined as central foveal thickness (CST) ≥325 micrometres (μm) on spectral-domain optical coherence tomography (SD-OCT). Composite strategy (i.e., considered to be an event) was applied to participants who received supplemental or prohibited therapy or PRP in the study eye. The rate of participants was calculated using the Kaplan-Meier (KM) method.

Outcome measures

Measure	PDS With Ranibizumab 100 mg/mL n=106 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm n=68 Participants Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Rate of Participants Developing a Vision-Threatening Complication or Center-involved Diabetic Macular Edema (CI-DME) Through Week 52	7.1 percentage of participants	47.0 percentage of participants

SECONDARY outcome

Timeframe: From Baseline through Week 52

Population: ITT Population included all participants who were randomized. Participants were grouped according to treatment assigned at randomization.

The KM method was used for analysis, and estimates are in terms of event rate. Composite strategy (i.e., considered to be an event) was applied to participants who received supplemental or prohibited therapy or PRP in the study eye.

Outcome measures

Measure	PDS With Ranibizumab 100 mg/mL n=106 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm n=68 Participants Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Rate of Participants Developing PDR or ASNV Through Week 52	1.0 percentage of participants	42.4 percentage of participants

SECONDARY outcome

Timeframe: From Baseline through Week 52

Population: ITT Population included all participants who were randomized. Participants were grouped according to treatment assigned at randomization.

CI-DME is defined as CST ≥325 μm on SD-OCT. The KM method was used for analysis, and estimated in terms of event rate. Composite strategy (i.e., considered to be an event) was applied to participants who received supplemental or prohibited therapy or PRP in the study eye.

Outcome measures

Measure	PDS With Ranibizumab 100 mg/mL n=106 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm n=68 Participants Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Rate of Participants Developing CI-DME Through Week 52	7.1 percentage of participants	47.0 percentage of participants

SECONDARY outcome

Timeframe: From Baseline through Week 52

Population: ITT Population included all participants who were randomized. Participants were grouped according to treatment assigned at randomization.

ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR ), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy. Composite strategy (i.e., considered to be an event) was applied to participants who received supplemental or prohibited therapy or PRP in the study eye. The rate of participants developing ≥ 2-step worsening on the ETDRS-DRSS was calculated using the KM method.

Outcome measures

Measure	PDS With Ranibizumab 100 mg/mL n=106 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm n=68 Participants Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Rate of Participants Developing a ≥ 2-Step Worsening From Baseline on the ETDRS-DRSS Through Week 52	3.0 percentage of participants	46.4 percentage of participants

SECONDARY outcome

Timeframe: Week 52

Population: ITT Population included all participants who were randomized. Participants were grouped according to treatment assigned at randomization.

ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR ), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy. Participants receiving supplemental treatments, prohibited therapy, or panretinal photocoagulation (PRP) were considered non-responders. Missing values not preceded by these intercurrent events were imputed using the last observation carried forward method. Percentages are rounded off to the nearest decimal point.

Outcome measures

Measure	PDS With Ranibizumab 100 mg/mL n=106 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm n=68 Participants Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Percentage of Participants With a ≥ 3-Step Improvement From Baseline on the ETDRS-DRSS at Week 52	15.1 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: From Baseline through Week 52

Population: ITT Population included all participants who were randomized. Participants were grouped according to treatment assigned at randomization.

ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR ), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy. Composite strategy (i.e., considered to be an event) was applied to participants who received supplemental or prohibited therapy or PRP in the study eye. The rate of participants developing ≥ 3-step worsening on the ETDRS-DRSS was calculated using the KM method.

Outcome measures

Measure	PDS With Ranibizumab 100 mg/mL n=106 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm n=68 Participants Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Rate of Participants Developing a ≥ 3-Step Worsening From Baseline on the ETDRS-DRSS Through Week 52	3.0 percentage of participants	45.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Week 112

ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale , from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 112

ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR ), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale , from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 112

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 112

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 112

CI-DME is defined as CST ≥325 μm on SD-OCT.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 112

ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 112

ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 112

BCVA was measured at a starting test distance of 4 meters using a set of three Precision Vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R). The BCVA letter score ranges from 0 to 100 (best score attainable), and a higher score indicates better visual acuity.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 112

BCVA was measured at a starting test distance of 4 meters using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R). The BCVA letter score ranges from 0 to 100 (best score attainable), and a higher score indicates better visual acuity.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 112

BCVA is measured using the ETDRS visual acuity chart starting at a test distance of 4 meters. The number of letters read correctly, Snellen fraction are converted to a decimal scale. There are 11 lines on a standard Snellen chart ranging from 0.1 (20/200) at worst to 2.0 (20/10) at best. 20/20 on the decimal scale is equal to 1.0. The higher the number of letters read correctly (higher number on the decimal scale), the better the vision (or visual acuity). The Snellen equivalent of 20/40 or better is 69 or more letters correctly read in the ETDRS chart.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 112

CST is defined as the average thickness of the central 1 millimeter (mm) circle of the ETDRS grid centered on the fovea measured between the internal limiting membrane and the Bruch's membrane. CST is measured using spectral domain optical coherence tomography (SD-OCT). A central reading center graded the SD-OCT digital images. A negative change from baseline value represents a reduction in macular edema.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 112

Total macular volume in cubic millimeter (mm^3), is the calculated volume from the layers of the retina based off OCT imaging. TMV is measured using SD-OCT.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug through Week 52

Population: Safety Evaluable Population in the PDS arm included all participants randomized to PDS receiving at least one loading dose, or any participant who received the PDS implant prior to Week 52.

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product,regardless of causal attribution.An adverse event can therefore be any unfavourable & unintended sign,symptom,or disease temporally associated with the use of a pharmaceutical product,whether considered related to the pharmaceutical product.Preexisting conditions which worsen during a study are also considered as adverse events.Ocular AEs are the events which are localized in the ocular region,graded according to the AE Severity Grading Scale as Mild:discomfort noticed,but no disruption of normal daily activity;Moderate:Discomfort sufficient to reduce or affect normal daily activity;Severe incapacitating with inability to work or to perform normal daily activity.Number of participants with ocular AEs in the study eye are reported in this outcome measure.As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only.

Outcome measures

Measure	PDS With Ranibizumab 100 mg/mL n=105 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Number of Participants With Ocular Adverse Events (AEs) and Severity of Ocular AEs in the PDS Arm Ocular AEs	84 Participants	—
Number of Participants With Ocular Adverse Events (AEs) and Severity of Ocular AEs in the PDS Arm Ocular AEs: Mild	55 Participants	—
Number of Participants With Ocular Adverse Events (AEs) and Severity of Ocular AEs in the PDS Arm Ocular AEs: Moderate	21 Participants	—
Number of Participants With Ocular Adverse Events (AEs) and Severity of Ocular AEs in the PDS Arm Ocular AEs: Severe	8 Participants	—

SECONDARY outcome

Timeframe: From first dose of study drug through Week 52

Population: Safety Evaluable (SE) Population in the PDS arm included all participants randomized to PDS receiving at least one loading dose, or any participant who received the PDS implant prior to Week 52.

An adverse event is any untoward medical occurrence in a clinical investigation participant subject administered a pharmaceutical product, regardless of causal attribution. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only.

Outcome measures

Measure	PDS With Ranibizumab 100 mg/mL n=105 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Number of Participants With Non-ocular AEs in the PDS Arm	59 Participants	—

SECONDARY outcome

Timeframe: From first dose of study drug through Week 52

Population: SE Population in the PDS arm included all participants randomized to PDS receiving at least one loading dose, or any participant who received the PDS implant prior to Week 52.

An AE is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Ocular AESI include vitreous hemorrhage; endophthalmitis; retinal detachment; conjunctival retraction; conjunctival erosion; conjunctival bleb or conjunctival filtering bleb leak; hyphema; cataract; device dislocation. As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only.

Outcome measures

Measure	PDS With Ranibizumab 100 mg/mL n=105 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Number of Participants With At Least One Ocular Adverse Events of Special Interest (AESI) in the PDS Arm	17 Participants	—

SECONDARY outcome

Timeframe: From Day 1 to Day 37 Postoperative Period

Population: SE Population in the PDS arm included all participants randomized to PDS receiving at least one loading dose, or any participant who received the PDS implant prior to Week 52.

An AE is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Ocular AESI include vitreous hemorrhage; endophthalmitis; retinal detachment; conjunctival retraction; conjunctival erosion; conjunctival bleb or conjunctival filtering bleb leak; hyphema; cataract; device dislocation. The ocular AESIs in the study eye were categorized based on onset as, Postoperative Period: onset within 37 days post initial implantation. As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only.

Outcome measures

Measure	PDS With Ranibizumab 100 mg/mL n=105 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Number of Participants With At Least One Ocular AESI During the Postoperative Period in the PDS Arm Postoperative Period	10 Participants	—
Number of Participants With At Least One Ocular AESI During the Postoperative Period in the PDS Arm Follow-up Period	9 Participants	—

SECONDARY outcome

Timeframe: Baseline up to week 112

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Baseline and multiple time points up to week 112

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to week 112

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 112

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 112

The numbers of ADA-positive participants at baseline and after drug administration were to be summarized for participants exposed to Ranibizumab. PDS patients who were ADA positive at the reference visit and ADA titer increased after implant; in this case, the titer of one or more samples collected after implant must be at least 4-fold greater than the titer of the reference visit sample. These patients are considered to have treatment-enhanced ADA responses.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 112

The numbers of neutralizing antibodies positive participants at baseline and after drug administration were to be summarized for participants exposed to Ranibizumab.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 112

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug through Week 52

Population: SE Population in the PDS arm included all participants randomized to PDS receiving at least one loading dose, or any participant who received the PDS implant prior to Week 52.

An AE related to study device or procedure is defined as any adverse event related to the use of an investigational medical device. This includes any adverse events resulting from insufficient or inadequate instructions for use, deployment, implantation, installation, operation, or any malfunction of the investigational medical device and any adverse event resulting from use error or from intentional misuse of the investigational medical device. PDS Device refers to the implant, insertion tool, initial fill needle, refill needle, and explant tool. PDS Procedure refers to the initial fill, implant insertion, refill-exchange, and explantation. As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only. Percentages are rounded off to the nearest decimal point.

Outcome measures

Measure	PDS With Ranibizumab 100 mg/mL n=105 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Percentage of Participants With At Least One AE Related to Study Device or Procedure in the PDS Arm	70.5 percentage of participants	—

SECONDARY outcome

Timeframe: From Day 1 up to Week 52

Population: SE Population in the PDS arm included all participants randomized to PDS receiving at least one loading dose, or any participant who received the PDS implant prior to Week 52.

An AE related to study device or procedure is defined as any AE related to the use of an investigational medical device & includes any AE resulting from insufficient or inadequate instructions for use, deployment, implantation, installation, operation, or any malfunction of the investigational medical device & any AE resulting from use error or from intentional misuse of the investigational medical device. PDS refers to the implant, insertion tool, initial fill needle, refill needle & explant tool. PDS procedure refers to the initial fill, implant insertion, refill-exchange, & explantation. Any AE related to study device or procedure that resulted in any of a serious AE such as death, life-threatening illness or injury or permanent impairment of a body structure or a body function was considered serious. As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only. Percentages are rounded off to the nearest decimal point.

Outcome measures

Measure	PDS With Ranibizumab 100 mg/mL n=105 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Percentage of Participants With Serious Adverse Effects Related to Study Device or Procedure in the PDS Arm	1.0 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline up to Week 112

Absence of intraretinal fluid and subretinal fluid are measured in the central 1 mm subfield on SD-OCT. Percentages are rounded off to the nearest decimal point.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 52

Population: ITT Population included all participants who were randomized. Overall number analyzed is the number of participants who completed the questionnaire.

The PPPQ is a 3-item questionnaire that captures a participant's preference for treatment (PDS or intravitreal injections), the strength of their preference (very strong, fairly strong, and not very strong) and the reasons for their preference (less worry or nervousness, requires less time for treatment, less discomfort, fewer treatments and other reason). As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only. Percentages are rounded off to the nearest decimal point.

Outcome measures

Measure	PDS With Ranibizumab 100 mg/mL n=94 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Percentage of Participants Who Report Preferring PDS Treatment to Intravitreal Ranibizumab Treatment, as Measured by the PDS Patient Preference Questionnaire (PPPQ) at Week 52	76.6 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: SE Population in the PDS arm included all participants randomized to PDS receiving at least one loading dose, or any participant who received the PDS implant prior to Week 52. Overall number analyzed is the number of participants implanted after 14 June 2021.

A device deficiency is defined as any inadequacy with respect to labeling, identity, quality, durability, reliability, usability, safety, or performance of an investigational device, including malfunctions, use errors, or inadequacy in information supplied by the manufacturer. As prespecified in the protocol, this outcome measure was applicable to participants in the PDS arm only and device deficiencies were to be recorded in the electronic capture system (EDC) after implementation of protocol Version 2 (i.e., for participants implanted after 14 June 2021).

Outcome measures

Measure	PDS With Ranibizumab 100 mg/mL n=47 Participants Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.	Comparator Arm Participants underwent study visits Q4W for observation and comprehensive clinical monitoring for the first 60 weeks. Thereafter, participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was scheduled at Week 60 followed by the second dose at Week 64. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Number of Participants With Device Deficiencies	9 Participants	—

Adverse Events

PDS With Ranibizumab 100 mg/mL

Serious events: 17 serious events

Other events: 89 other events

Deaths: 0 deaths

Serious adverse events

Measure	PDS With Ranibizumab 100 mg/mL n=105 participants at risk Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Cardiac disorders Acute myocardial infarction	0.00% 0/105 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Cardiac disorders Angina unstable	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Cardiac disorders Atrial fibrillation	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Cardiac disorders Cardiac failure congestive	2.9% 3/105 • Number of events 3 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Cardiac disorders Coronary artery disease	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Cataract	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Diabetic retinopathy	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Ocular hypertension	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Retinal artery occlusion	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Retinal detachment	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Vitreous haemorrhage	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Gastrointestinal disorders Constipation	0.00% 0/105 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Infections and infestations COVID-19	0.00% 0/105 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Infections and infestations Cellulitis	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Infections and infestations Osteomyelitis	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Infections and infestations Sepsis	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Metabolism and nutrition disorders Dehydration	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/105 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Musculoskeletal and connective tissue disorders Pain in extremity	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer stage I	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Nervous system disorders Cerebrovascular accident	0.00% 0/105 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Nervous system disorders Presyncope	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Nervous system disorders Syncope	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Nervous system disorders Transient ischaemic attack	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Renal and urinary disorders Acute kidney injury	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Renal and urinary disorders End stage renal disease	0.00% 0/105 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Reproductive system and breast disorders Prostatitis	0.00% 0/105 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Skin and subcutaneous tissue disorders Skin ulcer	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Vascular disorders Hypertension	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Vascular disorders Peripheral artery occlusion	0.95% 1/105 • Number of events 1 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.

Other adverse events

Measure	PDS With Ranibizumab 100 mg/mL n=105 participants at risk Participants received two loading doses of ranibizumab, 0.5 mg, as IVT before the PDS implant procedure. The first loading dose was on Day 1 followed by the second dose at Week 4. The PDS implant (pre-filled with ranibizumab 100 mg/mL) was surgically inserted 1 to 14 days after the second loading dose. Participants underwent PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) Q36W thereafter until the end of study.
Eye disorders Cataract	5.7% 6/105 • Number of events 8 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Conjunctival haemorrhage	75.2% 79/105 • Number of events 93 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Conjunctival hyperaemia	11.4% 12/105 • Number of events 12 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Conjunctival oedema	9.5% 10/105 • Number of events 10 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Diabetic retinal oedema	5.7% 6/105 • Number of events 7 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Diabetic retinopathy	6.7% 7/105 • Number of events 8 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Eye pain	8.6% 9/105 • Number of events 15 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Foreign body sensation in eyes	8.6% 9/105 • Number of events 9 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Iritis	9.5% 10/105 • Number of events 10 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Ocular hypertension	6.7% 7/105 • Number of events 9 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Punctate keratitis	9.5% 10/105 • Number of events 14 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Vitreous detachment	8.6% 9/105 • Number of events 10 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Eye disorders Vitreous haemorrhage	13.3% 14/105 • Number of events 14 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Infections and infestations COVID-19	15.2% 16/105 • Number of events 16 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Infections and infestations Sinusitis	6.7% 7/105 • Number of events 7 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Nervous system disorders Headache	8.6% 9/105 • Number of events 11 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.
Vascular disorders Hypertension	7.6% 8/105 • Number of events 8 • From study start through primary completion date (up to Week 52) All-cause mortality:ITT.Serious \& other AEs:SE Population.Per-protocol,AE collection began after 1st study treatment(ST) besides limited key exceptions;ST was mandatory for PDS arm.In Comparator arm (CA),27of 68 participants received ST \& reported all AEs; safety follow-up for them varied through Week 52(8-356 days). The remaining 41 participants in CA were not required to report all AEs, precluding a complete AE analysis.AEs for all implanted participants will be provided at the final analysis.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER