Trial Outcomes & Findings for A Phase III Study to Evaluate the Port Delivery System With Ranibizumab Compared With Monthly Ranibizumab Injections in Participants With Wet Age-Related Macular Degeneration (NCT NCT03677934)
NCT ID: NCT03677934
Last Updated: 2022-10-04
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
415 participants
Primary outcome timeframe
Baseline, and the average of Week 36 and Week 40
Results posted on
2022-10-04
Participant Flow
Participant milestones
| Measure |
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
|
Intravitreal Arm
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Overall Study
STARTED
|
248
|
167
|
|
Overall Study
COMPLETED
|
234
|
154
|
|
Overall Study
NOT COMPLETED
|
14
|
13
|
Reasons for withdrawal
| Measure |
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
|
Intravitreal Arm
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Death
|
8
|
4
|
|
Overall Study
Lost to Follow-up
|
3
|
0
|
|
Overall Study
Non-Compliance With Study Drug
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
7
|
Baseline Characteristics
A Phase III Study to Evaluate the Port Delivery System With Ranibizumab Compared With Monthly Ranibizumab Injections in Participants With Wet Age-Related Macular Degeneration
Baseline characteristics by cohort
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
Total
n=415 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
26 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
43 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
222 Participants
n=99 Participants
|
150 Participants
n=107 Participants
|
372 Participants
n=206 Participants
|
|
Age, Continuous
|
75.2 Years
STANDARD_DEVIATION 8.11 • n=99 Participants
|
74.8 Years
STANDARD_DEVIATION 7.63 • n=107 Participants
|
75.0 Years
STANDARD_DEVIATION 7.91 • n=206 Participants
|
|
Sex: Female, Male
Female
|
145 Participants
n=99 Participants
|
100 Participants
n=107 Participants
|
245 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
103 Participants
n=99 Participants
|
67 Participants
n=107 Participants
|
170 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
240 Participants
n=99 Participants
|
159 Participants
n=107 Participants
|
399 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
240 Participants
n=99 Participants
|
161 Participants
n=107 Participants
|
401 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, and the average of Week 36 and Week 40The 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.
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
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
|
0.2 letters
Interval -0.7 to 1.1
|
0.5 letters
Interval -0.6 to 1.6
|
SECONDARY outcome
Timeframe: Baseline, Week60, Week 64Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Change From Baseline in BCVA Score Averaged Over Week 60 and Week 64
|
-0.4 letters
Interval -1.5 to 0.7
|
-0.8 letters
Interval -2.2 to 0.6
|
SECONDARY outcome
Timeframe: Baseline up to Week 96Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Change From Baseline in BCVA Score Over Time
Week 84
|
-0.8 letters
Standard Deviation 0.62
|
0.3 letters
Standard Deviation 0.77
|
|
Change From Baseline in BCVA Score Over Time
Week 4
|
-4.3 letters
Standard Deviation 0.47
|
-0.4 letters
Standard Deviation 0.58
|
|
Change From Baseline in BCVA Score Over Time
Week 8
|
-1.7 letters
Standard Deviation 0.41
|
0.1 letters
Standard Deviation 0.51
|
|
Change From Baseline in BCVA Score Over Time
Week 12
|
-0.4 letters
Standard Deviation 0.39
|
0.6 letters
Standard Deviation 0.48
|
|
Change From Baseline in BCVA Score Over Time
Week 16
|
-0.6 letters
Standard Deviation 0.41
|
0.2 letters
Standard Deviation 0.5
|
|
Change From Baseline in BCVA Score Over Time
Week 20
|
-0.3 letters
Standard Deviation 0.42
|
0.1 letters
Standard Deviation 0.52
|
|
Change From Baseline in BCVA Score Over Time
Week 24
|
-0.6 letters
Standard Deviation 0.47
|
0.8 letters
Standard Deviation 0.57
|
|
Change From Baseline in BCVA Score Over Time
Week 28
|
-0.1 letters
Standard Deviation 0.47
|
0.5 letters
Standard Deviation 0.57
|
|
Change From Baseline in BCVA Score Over Time
Week 32
|
0.2 letters
Standard Deviation 0.49
|
0.9 letters
Standard Deviation 0.60
|
|
Change From Baseline in BCVA Score Over Time
Week 36
|
0.2 letters
Standard Deviation 0.47
|
0.3 letters
Standard Deviation 0.58
|
|
Change From Baseline in BCVA Score Over Time
Week 40
|
0.2 letters
Standard Deviation 0.51
|
0.7 letters
Standard Deviation 0.63
|
|
Change From Baseline in BCVA Score Over Time
Week 44
|
-0.1 letters
Standard Deviation 0.53
|
0.6 letters
Standard Deviation 0.65
|
|
Change From Baseline in BCVA Score Over Time
Week 48
|
0.0 letters
Standard Deviation 0.53
|
-0.2 letters
Standard Deviation 0.65
|
|
Change From Baseline in BCVA Score Over Time
Week 52
|
0.1 letters
Standard Deviation 0.54
|
-0.8 letters
Standard Deviation 0.67
|
|
Change From Baseline in BCVA Score Over Time
Week 56
|
0.1 letters
Standard Deviation 0.56
|
-0.5 letters
Standard Deviation 0.67
|
|
Change From Baseline in BCVA Score Over Time
Week 60
|
-0.5 letters
Standard Deviation 0.58
|
-0.8 letters
Standard Deviation 0.71
|
|
Change From Baseline in BCVA Score Over Time
Week 64
|
-0.3 letters
Standard Deviation 0.59
|
-0.7 letters
Standard Deviation 0.72
|
|
Change From Baseline in BCVA Score Over Time
Week 68
|
-0.5 letters
Standard Deviation 0.64
|
-0.3 letters
Standard Deviation 0.79
|
|
Change From Baseline in BCVA Score Over Time
Week 72
|
-0.3 letters
Standard Deviation 0.64
|
0.1 letters
Standard Deviation 0.79
|
|
Change From Baseline in BCVA Score Over Time
Week 76
|
-1.0 letters
Standard Deviation 0.68
|
0.2 letters
Standard Deviation 0.83
|
|
Change From Baseline in BCVA Score Over Time
Week 80
|
-0.7 letters
Standard Deviation 0.64
|
-0.2 letters
Standard Deviation 0.79
|
|
Change From Baseline in BCVA Score Over Time
Week 88
|
-1.3 letters
Standard Deviation 0.62
|
0.0 letters
Standard Deviation 0.76
|
|
Change From Baseline in BCVA Score Over Time
Week 92
|
-0.9 letters
Standard Deviation 0.63
|
-1.0 letters
Standard Deviation 0.78
|
|
Change From Baseline in BCVA Score Over Time
Week 96
|
-1.1 letters
Standard Deviation 0.68
|
-1.3 letters
Standard Deviation 0.84
|
SECONDARY outcome
Timeframe: Baseline, and the average of Week 36 and Week 40Population: 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
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
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
|
1.2 Percentage of participants
Interval 0.0 to 2.6
|
1.8 Percentage of participants
Interval 0.0 to 3.9
|
SECONDARY outcome
Timeframe: Baseline up to Week 96Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Percentage of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Over Time
|
2.7 Percentage of Participants
|
5.3 Percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline, and the average of Week 36 and Week 40Population: 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
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
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
|
80.7 Percentage of participants
Interval 76.9 to 84.5
|
82.1 Percentage of participants
Interval 77.5 to 86.7
|
SECONDARY outcome
Timeframe: Baseline up to Week 96Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Over Time
|
75.6 Percentage of participants
|
78.1 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, and the average of Week 36 and Week 40Population: 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
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40
Loss of Visual Function <10 letters
|
95.1 Percentage of participants
Interval 92.4 to 97.8
|
95.1 Percentage of participants
Interval 91.8 to 98.4
|
|
Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40
Loss of Visual Function <5 letters
|
85.0 Percentage of participants
Interval 80.5 to 89.4
|
88.3 Percentage of participants
Interval 83.4 to 93.3
|
SECONDARY outcome
Timeframe: Baseline up to Week 96Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline Over Time
<10 letters
|
88.9 Percentage of participants
|
84.1 Percentage of participants
|
|
Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline Over Time
< 5 letters
|
75.1 Percentage of participants
|
73.5 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 40Population: 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
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40
|
57.8 Percentage of participants
Interval 51.8 to 63.7
|
58.9 Percentage of participants
Interval 51.4 to 66.4
|
SECONDARY outcome
Timeframe: Baseline up to Week 96Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline Over Time
|
52.4 Percentage of Participants
|
55.6 Percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline to Week 36Population: 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.
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Change From Baseline in Center Point Thickness (CPT) at Week 36
Baseline Value
|
176.9 microns
Standard Deviation 3.48
|
177.4 microns
Standard Deviation 3.84
|
|
Change From Baseline in Center Point Thickness (CPT) at Week 36
Week 36
|
5.4 microns
Standard Deviation 2.91
|
2.6 microns
Standard Deviation 3.56
|
SECONDARY outcome
Timeframe: Baseline up to Week 96Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Change From Baseline in CPT Over Time
Baseline Value
|
176.9 microns
Standard Deviation 3.48
|
177.4 microns
Standard Deviation 3.84
|
|
Change From Baseline in CPT Over Time
Week 4
|
0.2 microns
Standard Deviation 2.05
|
2.1 microns
Standard Deviation 2.51
|
|
Change From Baseline in CPT Over Time
Week 8
|
0.3 microns
Standard Deviation 2.17
|
3.0 microns
Standard Deviation 2.66
|
|
Change From Baseline in CPT Over Time
Week 12
|
5.3 microns
Standard Deviation 2.87
|
0.3 microns
Standard Deviation 3.52
|
|
Change From Baseline in CPT Over Time
Week 16
|
6.0 microns
Standard Deviation 3.45
|
7.3 microns
Standard Deviation 4.23
|
|
Change From Baseline in CPT Over Time
Week 20
|
6.5 microns
Standard Deviation 2.7
|
1.3 microns
Standard Deviation 3.31
|
|
Change From Baseline in CPT Over Time
Week 24
|
6.7 microns
Standard Deviation 2.5
|
-0.8 microns
Standard Deviation 3.06
|
|
Change From Baseline in CPT Over Time
Week 28
|
-0.4 microns
Standard Deviation 2.5
|
1.6 microns
Standard Deviation 3.07
|
|
Change From Baseline in CPT Over Time
Week 32
|
4.5 microns
Standard Deviation 2.69
|
2.3 microns
Standard Deviation 3.29
|
|
Change From Baseline in CPT Over Time
Week 36
|
5.4 microns
Standard Deviation 2.91
|
2.7 microns
Standard Deviation 3.56
|
|
Change From Baseline in CPT Over Time
Week 40
|
9.0 microns
Standard Deviation 3.37
|
5.1 microns
Standard Deviation 4.13
|
|
Change From Baseline in CPT Over Time
Week 44
|
7.3 microns
Standard Deviation 3.13
|
3.4 microns
Standard Deviation 3.84
|
|
Change From Baseline in CPT Over Time
Week 48
|
8.9 microns
Standard Deviation 3.55
|
6.4 microns
Standard Deviation 4.36
|
|
Change From Baseline in CPT Over Time
Week 52
|
3.2 microns
Standard Deviation 3.43
|
6.6 microns
Standard Deviation 4.2
|
|
Change From Baseline in CPT Over Time
Week 56
|
2.7 microns
Standard Deviation 3.36
|
3.3 microns
Standard Deviation 4.10
|
|
Change From Baseline in CPT Over Time
Week 60
|
3.9 microns
Standard Deviation 3.39
|
2.5 microns
Standard Deviation 4.12
|
|
Change From Baseline in CPT Over Time
Week 64
|
5.5 microns
Standard Deviation 3.54
|
3.6 microns
Standard Deviation 4.34
|
|
Change From Baseline in CPT Over Time
Week 68
|
8.4 microns
Standard Deviation 3.48
|
2.1 microns
Standard Deviation 4.27
|
|
Change From Baseline in CPT Over Time
Week 72
|
8.1 microns
Standard Deviation 3.35
|
0.9 microns
Standard Deviation 4.14
|
|
Change From Baseline in CPT Over Time
Week 76
|
3.4 microns
Standard Deviation 3.61
|
0.1 microns
Standard Deviation 4.44
|
|
Change From Baseline in CPT Over Time
Week 80
|
6.1 microns
Standard Deviation 3.56
|
-2.7 microns
Standard Deviation 4.38
|
|
Change From Baseline in CPT Over Time
Week 84
|
8.4 microns
Standard Deviation 3.87
|
-2.0 microns
Standard Deviation 4.76
|
|
Change From Baseline in CPT Over Time
Week 88
|
9.8 microns
Standard Deviation 3.88
|
-0.6 microns
Standard Deviation 4.77
|
|
Change From Baseline in CPT Over Time
Week 92
|
10.3 microns
Standard Deviation 3.57
|
-1.3 microns
Standard Deviation 4.39
|
|
Change From Baseline in CPT Over Time
Week 96
|
9.9 microns
Standard Deviation 3.64
|
-1.3 microns
Standard Deviation 4.48
|
SECONDARY outcome
Timeframe: Day 1 to Week 24, Week 25 to Week 48, Week 49 to Week 72, Week73 to Week 96Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Outcome measures
| Measure |
PDS Implant Arm
n=246 Participants
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
|
Intravitreal Arm
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
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
Day 1 to Week 24 · Need for supplemental treatment
|
4 Participants
|
—
|
|
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
Day 1 to Week 24 · No need for supplemental treatment
|
242 Participants
|
—
|
|
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
Week 25 to Week 48 · Need for supplemental treatment
|
13 Participants
|
—
|
|
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
Week 25 to Week 48 · No need for supplemental treatment
|
228 Participants
|
—
|
|
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
Week 49 to Week 72 · Need for supplemental treatment
|
12 Participants
|
—
|
|
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
Week 49 to Week 72 · No need for supplemental treatment
|
219 Participants
|
—
|
|
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
Week 73 to Week 96 · Need for supplemental treatment
|
12 Participants
|
—
|
|
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
Week 73 to Week 96 · No need for supplemental treatment
|
213 Participants
|
—
|
SECONDARY outcome
Timeframe: Week 16 to Week 92Population: Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Outcome measures
| Measure |
PDS Implant Arm
n=246 Participants
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
|
Intravitreal Arm
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Percentage of Participants in the PDS Implant Arm Who Undergo a Supplemental Treatment That Requires Subsequent Additional Supplemental Treatments During the Study
2 supplemental treatments
|
4.1 Percentage of Participants
|
—
|
|
Percentage of Participants in the PDS Implant Arm Who Undergo a Supplemental Treatment That Requires Subsequent Additional Supplemental Treatments During the Study
3 supplemental treatments
|
0.8 Percentage of Participants
|
—
|
|
Percentage of Participants in the PDS Implant Arm Who Undergo a Supplemental Treatment That Requires Subsequent Additional Supplemental Treatments During the Study
5 supplemental treatments
|
0.4 Percentage of Participants
|
—
|
SECONDARY outcome
Timeframe: Randomization to Week 96Population: Safety Population comprising all patients who receive the study treatment, with patients grouped according to treatment actually received.
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs
Non-Ocular Events
|
213 Participants
|
121 Participants
|
|
Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs
Ocular Events: Study Eye
|
242 Participants
|
87 Participants
|
|
Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs
Ocular Events: Fellow Eye
|
124 Participants
|
65 Participants
|
SECONDARY outcome
Timeframe: Randomization to Week 96Population: Safety Population comprising all patients who receive the study treatment, with patients grouped according to treatment actually received.
Percentage of Participants with Adverse Events of Special Interest
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Percentage of Participants With Adverse Events of Special Interest
Adverse Events of Special Interest in Study Eye
|
64 Participants
|
18 Participants
|
|
Percentage of Participants With Adverse Events of Special Interest
Adverse Events of Special Interest in Fellow Eye
|
21 Participants
|
6 Participants
|
|
Percentage of Participants With Adverse Events of Special Interest
Non-Ocular Adverse Events of Special Interest
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Randomization to Week 96Population: PK Population
Outcome measures
| Measure |
PDS Implant Arm
n=39 Participants
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
|
Intravitreal Arm
n=46 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Observed Serum Ranibizumab Concentrations at Specified Timepoints
Week 76
|
0.291 ng/mL
Geometric Coefficient of Variation 247
|
0.0500 ng/mL
Geometric Coefficient of Variation 127
|
|
Observed Serum Ranibizumab Concentrations at Specified Timepoints
Randomization
|
0.125 ng/mL
Geometric Coefficient of Variation 115
|
0.117 ng/mL
Geometric Coefficient of Variation 78.5
|
|
Observed Serum Ranibizumab Concentrations at Specified Timepoints
Week 24 prerefill-exchange
|
0.397 ng/mL
Geometric Coefficient of Variation 71.1
|
0.0592 ng/mL
Geometric Coefficient of Variation 180
|
|
Observed Serum Ranibizumab Concentrations at Specified Timepoints
Week 28
|
0.564 ng/mL
Geometric Coefficient of Variation 40.7
|
0.0581 ng/mL
Geometric Coefficient of Variation 178
|
|
Observed Serum Ranibizumab Concentrations at Specified Timepoints
Week 48 prerefill-exchange
|
0.289 ng/mL
Geometric Coefficient of Variation 90.6
|
0.0594 ng/mL
Geometric Coefficient of Variation 146
|
|
Observed Serum Ranibizumab Concentrations at Specified Timepoints
Week 52
|
0.499 ng/mL
Geometric Coefficient of Variation 41.7
|
0.0531 ng/mL
Geometric Coefficient of Variation 123
|
|
Observed Serum Ranibizumab Concentrations at Specified Timepoints
Week 72 prerefill-exchange
|
0.257 ng/mL
Geometric Coefficient of Variation 73.7
|
0.0376 ng/mL
Geometric Coefficient of Variation 152
|
|
Observed Serum Ranibizumab Concentrations at Specified Timepoints
Week 96
|
0.191 ng/mL
Geometric Coefficient of Variation 154
|
0.0680 ng/mL
Geometric Coefficient of Variation 157
|
SECONDARY outcome
Timeframe: Randomization to Week 96Population: 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.
AUC0-6M = Area Under the Concentration-Time Curve From 0 to 6 Months
Outcome measures
| Measure |
PDS Implant Arm
n=33 Participants
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
|
Intravitreal Arm
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Estimated PK Parameter Values AUC0-6M
|
59.42 day.ng/mL
Standard Deviation 21.11
|
—
|
SECONDARY outcome
Timeframe: Randomization to Week 96Population: 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.
Apparent terminal half-life
Outcome measures
| Measure |
PDS Implant Arm
n=7 Participants
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
|
Intravitreal Arm
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Estimated PK Parameter Value t1/2 After PDS Implant Insertion
|
442.29 day
Standard Deviation 276.92
|
—
|
SECONDARY outcome
Timeframe: Randomization to Week 96Population: 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.
Cmin = Minimum Serum Concentration
Outcome measures
| Measure |
PDS Implant Arm
n=33 Participants
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
|
Intravitreal Arm
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Estimated PK Parameter Value Cmin
|
0.31 ng/mL
Standard Deviation 0.08
|
—
|
SECONDARY outcome
Timeframe: Randomization to Week 96Population: 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.
Cmax = Maximum Serum Concentration
Outcome measures
| Measure |
PDS Implant Arm
n=33 Participants
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
|
Intravitreal Arm
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Estimated PK Parameter Value Cmax
|
0.47 ng/mL
Standard Deviation 0.16
|
—
|
SECONDARY outcome
Timeframe: Randomization to Week 96Population: 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
Outcome measures
| Measure |
PDS Implant Arm
n=248 Participants
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
|
Intravitreal Arm
n=167 Participants
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
|---|---|---|
|
Baseline Prevalence and Incidence of Treatment-Emergent ADA
Patients with a positive sample at time of entry into the study
|
5 Participants
|
8 Participants
|
|
Baseline Prevalence and Incidence of Treatment-Emergent ADA
Patients with no positive samples at time of entry into the study
|
238 Participants
|
154 Participants
|
|
Baseline Prevalence and Incidence of Treatment-Emergent ADA
Post-baseline Patients Positive for ADA
|
38 Participants
|
21 Participants
|
|
Baseline Prevalence and Incidence of Treatment-Emergent ADA
Treatment-induced ADA
|
33 Participants
|
15 Participants
|
|
Baseline Prevalence and Incidence of Treatment-Emergent ADA
Treatment-enhanced ADA
|
0 Participants
|
2 Participants
|
|
Baseline Prevalence and Incidence of Treatment-Emergent ADA
Treatment unaffected or reduced
|
5 Participants
|
6 Participants
|
|
Baseline Prevalence and Incidence of Treatment-Emergent ADA
Patients negative for ADA at all times in the study
|
209 Participants
|
144 Participants
|
Adverse Events
Intravitreal Arm
Serious events: 39 serious events
Other events: 58 other events
Deaths: 5 deaths
PDS Implant Arm
Serious events: 78 serious events
Other events: 225 other events
Deaths: 8 deaths
Serious adverse events
| Measure |
Intravitreal Arm
n=167 participants at risk
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
PDS Implant Arm
n=248 participants at risk
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
|
|---|---|---|
|
Eye disorders
Vitreous haemorrhage
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.81%
2/248 • Number of events 2 • Baseline up to 2 years
|
|
Eye disorders
Conjunctival erosion
|
0.00%
0/167 • Baseline up to 2 years
|
1.2%
3/248 • Number of events 4 • Baseline up to 2 years
|
|
Eye disorders
Retinal tear
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Eye disorders
Visual acuity reduced
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 4 • Baseline up to 2 years
|
|
Eye disorders
Cataract cortical
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Eye disorders
Conjunctival bleb
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Eye disorders
Corneal disorder
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Eye disorders
Retinal pigment epithelial tear
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Eye disorders
Rhegmatogenous retinal detachment
|
0.00%
0/167 • Baseline up to 2 years
|
0.81%
2/248 • Number of events 3 • Baseline up to 2 years
|
|
Eye disorders
Choroidal detachment
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Eye disorders
Necrotising retinitis
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Eye disorders
Visual impairment
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Infections and infestations
Endophthalmitis
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
1.6%
4/248 • Number of events 5 • Baseline up to 2 years
|
|
Injury, poisoning and procedural complications
Conjunctival retraction
|
0.00%
0/167 • Baseline up to 2 years
|
1.2%
3/248 • Number of events 3 • Baseline up to 2 years
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Infections and infestations
Pneumonia
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
2.8%
7/248 • Number of events 7 • Baseline up to 2 years
|
|
Infections and infestations
Sepsis
|
1.2%
2/167 • Number of events 2 • Baseline up to 2 years
|
1.2%
3/248 • Number of events 3 • Baseline up to 2 years
|
|
Infections and infestations
Urinary tract infection
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
2.4%
6/248 • Number of events 6 • Baseline up to 2 years
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/167 • Baseline up to 2 years
|
0.81%
2/248 • Number of events 2 • Baseline up to 2 years
|
|
Infections and infestations
Cellulitis
|
1.2%
2/167 • Number of events 2 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Cardiac disorders
Coronary artery disease
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
1.2%
3/248 • Number of events 3 • Baseline up to 2 years
|
|
Cardiac disorders
Atrial fibrillation
|
1.2%
2/167 • Number of events 2 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.81%
2/248 • Number of events 2 • Baseline up to 2 years
|
|
Gastrointestinal disorders
Pancreatitis
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
1.2%
3/248 • Number of events 3 • Baseline up to 2 years
|
|
Nervous system disorders
Cerebrovascular accident
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
1.6%
4/248 • Number of events 4 • Baseline up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/167 • Baseline up to 2 years
|
1.2%
3/248 • Number of events 4 • Baseline up to 2 years
|
|
Nervous system disorders
Syncope
|
1.8%
3/167 • Number of events 3 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Nervous system disorders
Disturbance in attention
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Nervous system disorders
Dizziness
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Nervous system disorders
Parkinson's disease
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Nervous system disorders
Temporal lobe epilepsy
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Injury, poisoning and procedural complications
Acetabulum fracture
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Injury, poisoning and procedural complications
Contusion
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/167 • Baseline up to 2 years
|
0.81%
2/248 • Number of events 2 • Baseline up to 2 years
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma stage I
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Penile squamous cell carcinoma
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin cancer
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small intestine adenocarcinoma
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of pharynx
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Metabolism and nutrition disorders
Dehydration
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Metabolism and nutrition disorders
Lactic acidosis
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Renal and urinary disorders
Acute kidney injury
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/167 • Baseline up to 2 years
|
0.81%
2/248 • Number of events 2 • Baseline up to 2 years
|
|
Renal and urinary disorders
Renal embolism
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Renal and urinary disorders
Renal infarct
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Renal and urinary disorders
Ureterolithiasis
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
1.2%
3/248 • Number of events 3 • Baseline up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Vascular disorders
Aortic stenosis
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Vascular disorders
Haematoma
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Vascular disorders
Hypertension
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Vascular disorders
Hypotension
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Reproductive system and breast disorders
Prostatitis
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Reproductive system and breast disorders
Prostatomegaly
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Blood and lymphatic system disorders
Anaemia
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Ear and labyrinth disorders
Vertigo positional
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Cardiac disorders
Acute myocardial infarction
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Cardiac disorders
Aortic valve incompetence
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Cardiac disorders
Cardiac arrest
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Cardiac disorders
Cardiac failure
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Cardiac disorders
Cardiac failure acute
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Cardiac disorders
Cardiac failure congestive
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Cardiac disorders
Myocardial infarction
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Eye disorders
Retinal artery occlusion
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Eye disorders
Retinal haemorrhage
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Eye disorders
Scleral thinning
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Gastrointestinal disorders
Mesenteric vein thrombosis
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
General disorders
Asthenia
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
General disorders
Chest pain
|
1.8%
3/167 • Number of events 3 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
General disorders
Death
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
General disorders
Mucosal inflammation
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
General disorders
Systemic inflammatory response syndrome
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Hepatobiliary disorders
Gallbladder rupture
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Infections and infestations
Arthritis infective
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Infections and infestations
Bacteraemia
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Infections and infestations
COVID-19
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Infections and infestations
COVID-19 pneumonia
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Infections and infestations
Influenza
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Infections and infestations
Kidney infection
|
0.60%
1/167 • Number of events 2 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Infections and infestations
Metapneumovirus pneumonia
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Infections and infestations
Pneumonia bacterial
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Infections and infestations
Post procedural infection
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Infections and infestations
Septic arthritis staphylococcal
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Infections and infestations
Septic shock
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer metastatic
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial adenocarcinoma
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/167 • Baseline up to 2 years
|
0.81%
2/248 • Number of events 2 • Baseline up to 2 years
|
|
Product Issues
Device dislocation
|
0.00%
0/167 • Baseline up to 2 years
|
1.2%
3/248 • Number of events 3 • Baseline up to 2 years
|
|
Surgical and medical procedures
Hip arthroplasty
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
0.00%
0/248 • Baseline up to 2 years
|
|
Vascular disorders
Aortic aneurysm
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Vascular disorders
Arteriosclerosis
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
|
Vascular disorders
Thrombosis
|
0.00%
0/167 • Baseline up to 2 years
|
0.40%
1/248 • Number of events 1 • Baseline up to 2 years
|
Other adverse events
| Measure |
Intravitreal Arm
n=167 participants at risk
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
PDS Implant Arm
n=248 participants at risk
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
|
|---|---|---|
|
Eye disorders
Conjunctival haemorrhage
|
7.2%
12/167 • Number of events 14 • Baseline up to 2 years
|
71.8%
178/248 • Number of events 193 • Baseline up to 2 years
|
|
Eye disorders
Conjunctival hyperaemia
|
1.8%
3/167 • Number of events 4 • Baseline up to 2 years
|
26.6%
66/248 • Number of events 71 • Baseline up to 2 years
|
|
Eye disorders
Iritis
|
0.60%
1/167 • Number of events 1 • Baseline up to 2 years
|
20.2%
50/248 • Number of events 55 • Baseline up to 2 years
|
|
Eye disorders
Eye pain
|
4.8%
8/167 • Number of events 8 • Baseline up to 2 years
|
10.1%
25/248 • Number of events 28 • Baseline up to 2 years
|
|
Eye disorders
Vitreous floaters
|
2.4%
4/167 • Number of events 4 • Baseline up to 2 years
|
9.3%
23/248 • Number of events 24 • Baseline up to 2 years
|
|
Eye disorders
Vitreous detachment
|
4.8%
8/167 • Number of events 11 • Baseline up to 2 years
|
6.9%
17/248 • Number of events 19 • Baseline up to 2 years
|
|
Eye disorders
Punctate keratitis
|
2.4%
4/167 • Number of events 6 • Baseline up to 2 years
|
6.9%
17/248 • Number of events 25 • Baseline up to 2 years
|
|
Eye disorders
Vitreous haemorrhage
|
1.8%
3/167 • Number of events 4 • Baseline up to 2 years
|
5.2%
13/248 • Number of events 14 • Baseline up to 2 years
|
|
Eye disorders
Neovascular age-related macular degeneration
|
9.0%
15/167 • Number of events 15 • Baseline up to 2 years
|
8.1%
20/248 • Number of events 20 • Baseline up to 2 years
|
|
Eye disorders
Foreign body sensation in eyes
|
1.2%
2/167 • Number of events 2 • Baseline up to 2 years
|
7.3%
18/248 • Number of events 20 • Baseline up to 2 years
|
|
Eye disorders
Hypotony of eye
|
0.00%
0/167 • Baseline up to 2 years
|
6.0%
15/248 • Number of events 15 • Baseline up to 2 years
|
|
Eye disorders
Conjunctival bleb
|
0.00%
0/167 • Baseline up to 2 years
|
6.5%
16/248 • Number of events 16 • Baseline up to 2 years
|
|
Infections and infestations
Nasopharyngitis
|
8.4%
14/167 • Number of events 15 • Baseline up to 2 years
|
5.2%
13/248 • Number of events 14 • Baseline up to 2 years
|
|
Nervous system disorders
Headache
|
2.4%
4/167 • Number of events 4 • Baseline up to 2 years
|
5.6%
14/248 • Number of events 14 • Baseline up to 2 years
|
Additional Information
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