A Phase III Study to Evaluate the Port Delivery System Wi... | NCT03677934

NCT03677934

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
PDS Implant Arm	Experimental	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals	Drug: PDS Implant filled with 100 mg/mL Ranibizumab
Intravitreal Arm	Active Comparator	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.	Drug: Intravitreal Injections of 10 mg/mL Ranibizumab

Name	Type	Description	Arm Group Labels	Other Names
PDS Implant filled with 100 mg/mL Ranibizumab	Drug	Will be administered as per the schedule described in individual arm.	PDS Implant Arm

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score at the Average of Week 36 and Week 40, as Assessed Using the ETDRS Visual Acuity Chart at a Starting Distance of 4 Meters	The primary efficacy endpoint is the change in BCVA score from baseline averaged over Weeks 36 and 40 with BCVA assessed using the ETDRS chart at a starting distance of 4 meters. ETDRS = Early Treatment Diabetic Retinopathy Study. The primary objective is to determine the NI and equivalence between the two treatment groups, as measured by the primary efficacy endpoint with a NI margin of 4.5 letters and equivalence margins of ± 4.5 letters. A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.	Baseline, and the average of Week 36 and Week 40

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in BCVA Score Averaged Over Week 60 and Week 64		Baseline, Week60, Week 64
Change From Baseline in BCVA Score Over Time		Baseline up to Week 96

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age ≥50 years, at time of signing Informed Consent Form
Initial diagnosis of exudative neovascular age-related macular degeneration (nAMD) within 9 months prior to the screening visit
Previous treatment with at least three anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections for nAMD per standard of care within 6 months prior to the screening visit
Demonstrated response to prior anti-VEGF intravitreal treatment since diagnosis
Best-corrected visual acuity (BCVA) of 34 letters or better

Exclusion Criteria:

Subfoveal fibrosis or subfoveal atrophy in study eye
Subretinal hemorrhage that involves the center of the fovea in study eye
History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in study eye
Prior treatment with Visudyne®, external-beam radiation therapy, or transpupillary thermotherapy in study eye
Previous intraocular device implantation in study eye
Previous laser (any type) used for AMD treatment in study eye
Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit in either eye
Prior participation in a clinical trial involving anti-VEGF drugs within 6 months prior to the randomization visit, other than ranibizumab in either eye
CNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia in either eye
Uncontrolled blood pressure
History of stroke within the last 3 months prior to informed consent
Uncontrolled atrial fibrillation within 3 months of informed consent
History of myocardial infarction within the last 3 months prior to informed consent
History of other disease, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the Implant and that might affect interpretation of the results of the study or renders the participant at high risk of treatment complications in the opinion of the investigator
Current systemic treatment for a confirmed active systemic infection
Chronic use of oral corticosteroids
Active cancer within 12 months of randomization
Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent (excluding vitamins and minerals)

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Barnet Dulaney Perkins Eye Center		Mesa	Arizona	85206	United States
Associated Retina Consultants

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
39447871	Derived	Sheth VS, Holekamp NM, Khanani AM, Rachitskaya A, Blotner S, Gune S, Heinrich D, Maass KF, Chakravarthy U. Retinal Fluid and Thickness Fluctuations in Archway Trial for Port Delivery System with Ranibizumab versus Monthly Ranibizumab Injections. Ophthalmol Retina. 2025 Apr;9(4):330-342. doi: 10.1016/j.oret.2024.10.015. Epub 2024 Oct 22.
39209113

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
FG001	Intravitreal Arm

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 2, 2021	Nov 18, 2021

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00075.2± 8.11 BG00174.8± 7.63 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000145 BG001100 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0007 BG0018 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001 BG0012 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score at the Average of Week 36 and Week 40, as Assessed Using the ETDRS Visual Acuity Chart at a Starting Distance of 4 Meters

The primary efficacy endpoint is the change in BCVA score from baseline averaged over Weeks 36 and 40 with BCVA assessed using the ETDRS chart at a starting distance of 4 meters. ETDRS = Early Treatment Diabetic Retinopathy Study.

The primary objective is to determine the NI and equivalence between the two treatment groups, as measured by the primary efficacy endpoint with a NI margin of 4.5 letters and equivalence margins of ± 4.5 letters.

A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.

Posted

Mean

95.03% Confidence Interval

letters

Baseline, and the average of Week 36 and Week 40

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000248 OG001167

Title

Denominators

Categories

Title	Measurements
	OG0000.2(-0.7 to 1.1) OG0010.5(-0.6 to 1.6)

Secondary

Change From Baseline in BCVA Score Averaged Over Week 60 and Week 64

Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received

Posted

Mean

95.03% Confidence Interval

letters

Baseline, Week60, Week 64

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in BCVA Score Over Time

Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received

Posted

Mean

Standard Deviation

letters

Baseline up to Week 96

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse at the Average Over Week 36 and Week 40

Adult patients with nAMD diagnosed within 9 months and receiving at least 4 anti-VEGF intravitreal injections (with the last injection being ranibizumab), responsive to prior anti-VEGF treatment

Posted

Number

95.03% Confidence Interval

Percentage of participants

Baseline, and the average of Week 36 and Week 40

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Over Time

Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received

Posted

Number

Percentage of Participants

Baseline up to Week 96

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better at the Average Over Week 36 and Week 40

Adult patients with nAMD diagnosed within 9 months and receiving at least 4 anti-VEGF intravitreal injections (with the last injection being ranibizumab), responsive to prior anti-VEGF treatment

Posted

Number

95.03% Confidence Interval

Percentage of participants

Baseline, and the average of Week 36 and Week 40

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Over Time

Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received

Posted

Number

Percentage of participants

Baseline up to Week 96

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40

Adult patients with nAMD diagnosed within 9 months and receiving at least 4 anti-VEGF intravitreal injections (with the last injection being ranibizumab), responsive to prior anti-VEGF treatment

Posted

Number

95.03% Confidence Interval

Percentage of participants

Baseline, and the average of Week 36 and Week 40

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline Over Time

Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received

Posted

Number

Percentage of participants

Baseline up to Week 96

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40

Adult patients with nAMD diagnosed within 9 months and receiving at least 4 anti-VEGF intravitreal injections (with the last injection being ranibizumab), responsive to prior anti-VEGF treatment

Posted

Number

95.03% Confidence Interval

Percentage of participants

Baseline up to Week 40

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline Over Time

Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received

Posted

Number

Percentage of Participants

Baseline up to Week 96

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Center Point Thickness (CPT) at Week 36

Adult patients with nAMD diagnosed within 9 months and receiving at least 4 anti-VEGF intravitreal injections (with the last injection being ranibizumab), responsive to prior anti-VEGF treatment. 14 participants (7 participants in each arm) discontinued before Week 36 or the CPT value was missing (or not able to be measured on image) for the week 36 visit.

Posted

Mean

Standard Deviation

microns

Baseline to Week 36

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in CPT Over Time

Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received

Posted

Mean

Standard Deviation

microns

Baseline up to Week 96

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants in the PDS Implant Arm Who Undergo Supplemental Treatment With Intravitreal Ranibizumab 0.5 mg Before the First, Second, Third, and Fourth Fixed Refill-Exchange Intervals

Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received

Posted

Count of Participants

Participants

Day 1 to Week 24, Week 25 to Week 48, Week 49 to Week 72, Week73 to Week 96

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals

Units	Counts
Participants	OG000

Secondary

Percentage of Participants in the PDS Implant Arm Who Undergo a Supplemental Treatment That Requires Subsequent Additional Supplemental Treatments During the Study

Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received

Posted

Number

Percentage of Participants

Week 16 to Week 92

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs

Safety Population comprising all patients who receive the study treatment, with patients grouped according to treatment actually received.

Posted

Count of Participants

Participants

Randomization to Week 96

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Adverse Events of Special Interest

Percentage of Participants with Adverse Events of Special Interest

Safety Population comprising all patients who receive the study treatment, with patients grouped according to treatment actually received.

Posted

Count of Participants

Participants

Randomization to Week 96

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000

Secondary

Observed Serum Ranibizumab Concentrations at Specified Timepoints

PK Population

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Randomization to Week 96

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Units	Counts
Participants	OG000

Secondary

Estimated PK Parameter Values AUC0-6M

AUC0-6M = Area Under the Concentration-Time Curve From 0 to 6 Months

PK Population excluding patients receiving intravitreal injections of ranibizumab in the study eye post PDS implant (including supplemental treatment), patients with fellow eye ranibizumab or bevacizumab treatment, or prior bevacizumab treatment in either eye.

Posted

Mean

Standard Deviation

day.ng/mL

Randomization to Week 96

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals

Units	Counts
Participants	OG000

Secondary

Estimated PK Parameter Value t1/2 After PDS Implant Insertion

Apparent terminal half-life

Posted

Mean

Standard Deviation

day

Randomization to Week 96

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals

Units	Counts
Participants	OG000

Secondary

Estimated PK Parameter Value Cmin

Cmin = Minimum Serum Concentration

Posted

Mean

Standard Deviation

ng/mL

Randomization to Week 96

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals

Units	Counts
Participants	OG000

Secondary

Estimated PK Parameter Value Cmax

Cmax = Maximum Serum Concentration

Posted

Mean

Standard Deviation

ng/mL

Randomization to Week 96

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals

Units	Counts
Participants	OG000

Secondary

Baseline Prevalence and Incidence of Treatment-Emergent ADA

The Biomarker Analysis Population consists of patients who are in the Safety Population and have sufficient data to enable assessment of potential changes in biomarkers in response to treatment during the conduct of this study. The analysis will group patients according to treatment actually received

Posted

Number

Participants

Randomization to Week 96

ID	Title	Description
OG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
OG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.	5	167	39	167	58	167
EG001	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals	8	248	78	248	225	248

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vitreous haemorrhage	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0012 events2 affected248 at risk
Conjunctival erosion	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0014 events3 affected248 at risk
Retinal tear	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0011 events1 affected248 at risk
Visual acuity reduced	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0014 events1 affected248 at risk
Cataract cortical	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Conjunctival bleb	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Corneal disorder	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Retinal pigment epithelial tear	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Rhegmatogenous retinal detachment	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0013 events2 affected248 at risk
Choroidal detachment	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Necrotising retinitis	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Visual impairment	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Endophthalmitis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0015 events4 affected248 at risk
Conjunctival retraction	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0013 events3 affected248 at risk
Facial bones fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0011 events1 affected248 at risk
Pneumonia	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0017 events7 affected248 at risk
Sepsis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected167 at risk EG0013 events3 affected248 at risk
Urinary tract infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0016 events6 affected248 at risk
Diverticulitis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0012 events2 affected248 at risk
Cellulitis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected167 at risk EG0010 events0 affected248 at risk
Coronary artery disease	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0013 events3 affected248 at risk
Atrial fibrillation	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected167 at risk EG0011 events1 affected248 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0012 events2 affected248 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0013 events3 affected248 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0014 events4 affected248 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0014 events3 affected248 at risk
Syncope	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected167 at risk EG0010 events0 affected248 at risk
Disturbance in attention	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Dizziness	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Ischaemic stroke	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Parkinson's disease	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Temporal lobe epilepsy	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Acetabulum fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0012 events2 affected248 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Pancreatic carcinoma stage I	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Penile squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Skin cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Small intestine adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Squamous cell carcinoma of pharynx	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0011 events1 affected248 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0011 events1 affected248 at risk
Lactic acidosis	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0011 events1 affected248 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0012 events2 affected248 at risk
Renal embolism	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Renal infarct	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0013 events3 affected248 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Aortic stenosis	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Haematoma	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Hypertension	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Hypotension	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Portal vein thrombosis	Hepatobiliary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Prostatitis	Reproductive system and breast disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Prostatomegaly	Reproductive system and breast disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Vertigo positional	Ear and labyrinth disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Angina unstable	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Aortic valve incompetence	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Bradycardia	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Cardiac arrest	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0011 events1 affected248 at risk
Cardiac failure	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0011 events1 affected248 at risk
Cardiac failure acute	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Myocardial infarction	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Retinal artery occlusion	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Retinal haemorrhage	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Scleral thinning	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Hiatus hernia	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Mesenteric vein thrombosis	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Vomiting	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Asthenia	General disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Chest pain	General disorders	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected167 at risk EG0010 events0 affected248 at risk
Death	General disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Mucosal inflammation	General disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Non-cardiac chest pain	General disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Gallbladder rupture	Hepatobiliary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Arthritis infective	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Bacteraemia	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
COVID-19	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Influenza	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Kidney infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0002 events1 affected167 at risk EG0010 events0 affected248 at risk
Metapneumovirus pneumonia	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Pneumonia bacterial	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Post procedural infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Septic arthritis staphylococcal	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Septic shock	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Colon cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Endometrial adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Hepatic cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0012 events2 affected248 at risk
Device dislocation	Product Issues	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0013 events3 affected248 at risk
Hip arthroplasty	Surgical and medical procedures	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 events0 affected248 at risk
Aortic aneurysm	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Arteriosclerosis	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk
Thrombosis	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 events1 affected248 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Conjunctival haemorrhage	Eye disorders	MedDRA v23.0	Systematic Assessment	EG00014 events12 affected167 at risk EG001193 events178 affected248 at risk
Conjunctival hyperaemia	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0004 events3 affected167 at risk EG00171 events66 affected248 at risk
Iritis	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected167 at risk EG00155 events50 affected248 at risk
Eye pain	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0008 events8 affected167 at risk EG00128 events25 affected248 at risk
Vitreous floaters	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0004 events4 affected167 at risk EG00124 events23 affected248 at risk
Vitreous detachment	Eye disorders	MedDRA v23.0	Systematic Assessment	EG00011 events8 affected167 at risk EG00119 events17 affected248 at risk
Punctate keratitis	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0006 events4 affected167 at risk EG00125 events17 affected248 at risk
Vitreous haemorrhage	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0004 events3 affected167 at risk EG00114 events13 affected248 at risk
Neovascular age-related macular degeneration	Eye disorders	MedDRA v23.0	Systematic Assessment	EG00015 events15 affected167 at risk EG00120 events20 affected248 at risk
Foreign body sensation in eyes	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected167 at risk EG00120 events18 affected248 at risk
Hypotony of eye	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG00115 events15 affected248 at risk
Conjunctival bleb	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected167 at risk EG00116 events16 affected248 at risk
Nasopharyngitis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG00015 events14 affected167 at risk EG00114 events13 affected248 at risk
Headache	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0004 events4 affected167 at risk EG00114 events14 affected248 at risk

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description
BG000	PDS Implant Arm	Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
BG001	Intravitreal Arm	Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
BG002	Total	Total of all reporting groups