Trial Outcomes & Findings for A Study to Investigate Vamikibart (RO7200220) in Combination With Ranibizumab in Diabetic Macular Edema (NCT NCT05151744)

Last Updated: 2025-10-16

Results Overview

BCVA was measured via Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters using a set of three Precision vision\^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity (VA) examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores and gain in BCVA from baseline indicate improvement in VA. This analysis used a Mixed Model for Repeated Measurements (MMRM) model.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

187 participants

Primary outcome timeframe

Baseline, Week 44 and Week 48

Results posted on

2025-10-16

Participant Flow

A total of 187 participants with diabetic macular edema (DME) took part in the study at 37 investigative sites across the United States, Argentina, Israel, South Korea, Poland, Canada, Spain, and the United Kingdom from 17 December 2021 to 1 October 2024.

Participants were randomized in 1:1 ratio to Vamikibart + Ranibizumab arm and Ranibizumab arm.

Participant milestones

Participant milestones
Measure	Arm A: Vamikibart + Ranibizumab Participants received vamikibart, 1 milligrams (mg) as intravitreal (IVT) injection, every 4 weeks (Q4W) in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Overall Study STARTED	93	94
Overall Study Previously-treated Intent-to-treat (ITT) Population	32	31
Overall Study Treatment-naive ITT Population	61	63
Overall Study COMPLETED	64	81
Overall Study NOT COMPLETED	29	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: Vamikibart + Ranibizumab Participants received vamikibart, 1 milligrams (mg) as intravitreal (IVT) injection, every 4 weeks (Q4W) in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Overall Study Adverse Event	6	2
Overall Study Death	1	2
Overall Study Lack of Efficacy	1	1
Overall Study Lost to Follow-up	2	2
Overall Study Need for Rescue Treatment	0	1
Overall Study Non-compliance with Study Drug	0	1
Overall Study Reason not Specified	10	0
Overall Study Physician Decision	2	1
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	6	3

Baseline Characteristics

A Study to Investigate Vamikibart (RO7200220) in Combination With Ranibizumab in Diabetic Macular Edema

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.	Total n=187 Participants Total of all reporting groups
Age, Continuous	61.7 years STANDARD_DEVIATION 10.1 • n=99 Participants	62.1 years STANDARD_DEVIATION 9.3 • n=107 Participants	61.9 years STANDARD_DEVIATION 9.7 • n=206 Participants
Sex: Female, Male Female	31 Participants n=99 Participants	39 Participants n=107 Participants	70 Participants n=206 Participants
Sex: Female, Male Male	62 Participants n=99 Participants	55 Participants n=107 Participants	117 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=99 Participants	14 Participants n=107 Participants	20 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	56 Participants n=99 Participants	56 Participants n=107 Participants	112 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	31 Participants n=99 Participants	24 Participants n=107 Participants	55 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 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	7 Participants n=99 Participants	3 Participants n=107 Participants	10 Participants n=206 Participants
Race (NIH/OMB) White	45 Participants n=99 Participants	60 Participants n=107 Participants	105 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	41 Participants n=99 Participants	31 Participants n=107 Participants	72 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline, Week 44 and Week 48

Population: Treatment naïve ITT population included all randomized participants who were IVT anti-vascular endothelial growth factor (anti-VEGF) or periocular/IVT corticosteroids treatment-naïve as defined in the exclusion criteria 9 and 10 in the protocol.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=61 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=63 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged Over Week 44 and Week 48 in Treatment-naïve Participants	12.8 letters Standard Error 1.30	9.4 letters Standard Error 1.25

SECONDARY outcome

Timeframe: Up to Week 72

Population: Safety Population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not.

An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Systemic AEs include all non-ocular AEs.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Number of Participants With Systemic and Ocular Adverse Events (AEs) Systemic AEs	54 Participants	60 Participants
Number of Participants With Systemic and Ocular Adverse Events (AEs) Ocular AEs in Study Eyes	33 Participants	28 Participants
Number of Participants With Systemic and Ocular Adverse Events (AEs) Ocular AEs in Fellow Eyes	25 Participants	27 Participants

SECONDARY outcome

Timeframe: Baseline, Week 44 and Week 48

Population: Previously treated ITT population included all randomized participants who were IVT anti-VEGF or periocular/IVT corticosteroids previously treated participants as defined in the exclusion criteria 9 and 10 in the protocol.

BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision\^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores and gain in BCVA from baseline indicate improvement in VA. This analysis used a MMRM model.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=32 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=31 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in BCVA Averaged Over Week 44 and Week 48 in Previously Treated Participants	11.1 letters Standard Error 1.50	8.4 letters Standard Error 1.49

SECONDARY outcome

Timeframe: Baseline, Week 44 and Week 48

Population: Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in BCVA Averaged Over Week 44 and Week 48 in Overall ITT Population	12.4 letters Standard Error 0.99	9.1 letters Standard Error 0.96

SECONDARY outcome

Timeframe: Baseline, Week 32 and Week 36

Population: Treatment-naïve ITT population included all randomized participants who were IVT anti-VEGF or periocular/IVT corticosteroids treatment-naïve as defined in the exclusion criteria 9 and 10 in the protocol.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=61 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=63 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Treatment-naïve Participants	11.8 letters Standard Error 0.97	9.3 letters Standard Error 0.94

SECONDARY outcome

Timeframe: Baseline, Week 32 and Week 36

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=32 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=31 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Previously Treated Participants	8.3 letters Standard Error 1.43	7.5 letters Standard Error 1.46

SECONDARY outcome

Timeframe: Baseline, Week 32 and Week 36

Population: Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Overall ITT Population	10.6 letters Standard Error 0.81	8.7 letters Standard Error 0.80

SECONDARY outcome

Timeframe: Baseline, Week 20 and Week 24

Population: Treatment naïve ITT population included all randomized participants who were IVT anti-VEGF or periocular/IVT corticosteroids treatment-naïve as defined in the exclusion criteria 9 and 10 in the protocol.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=61 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=63 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in BCVA Averaged Over Week 20 and Week 24 in Treatment-naïve Participants	10.6 letters Standard Error 1.04	8.5 letters Standard Error 1.01

SECONDARY outcome

Timeframe: Baseline, Week 20 and Week 24

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=32 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=31 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in BCVA Averaged Over Week 20 and Week 24 in Previously Treated Participants	8.1 letters Standard Error 1.46	6.2 letters Standard Error 1.47

SECONDARY outcome

Timeframe: Baseline, Week 20 and Week 24

Population: Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in BCVA Averaged Over Week 20 and Week 24, in Overall ITT Population	9.7 letters Standard Error 0.84	7.8 letters Standard Error 0.83

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

Population: Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in BCVA Over Time in Overall ITT Population Baseline	62.6 letters Standard Error 1.02	62.0 letters Standard Error 1.01
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 4	6.7 letters Standard Error 0.64	4.2 letters Standard Error 0.65
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 8	7.6 letters Standard Error 0.76	4.6 letters Standard Error 0.76
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 12	8.9 letters Standard Error 0.78	6.4 letters Standard Error 0.78
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 16	9.3 letters Standard Error 0.83	7.4 letters Standard Error 0.83
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 20	9.7 letters Standard Error 0.81	7.6 letters Standard Error 0.80
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 24	9.8 letters Standard Error 1.03	8.0 letters Standard Error 1.02
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 28	10.1 letters Standard Error 0.87	8.5 letters Standard Error 0.87
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 32	10.5 letters Standard Error 0.88	8.8 letters Standard Error 0.87
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 36	10.6 letters Standard Error 0.84	8.6 letters Standard Error 0.83
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 40	10.9 letters Standard Error 0.95	8.8 letters Standard Error 0.93
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 44	12.2 letters Standard Error 1.01	8.7 letters Standard Error 0.99
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 48	12.5 letters Standard Error 1.03	9.4 letters Standard Error 1.00
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 52	11.1 letters Standard Error 1.07	8.0 letters Standard Error 1.03
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 56	10.8 letters Standard Error 1.13	7.8 letters Standard Error 1.09
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 60	10.4 letters Standard Error 1.18	7.7 letters Standard Error 1.14
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 64	10.2 letters Standard Error 1.12	8.2 letters Standard Error 1.10
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 68	9.9 letters Standard Error 1.14	7.6 letters Standard Error 1.11
Change From Baseline in BCVA Over Time in Overall ITT Population Change at Week 72	9.2 letters Standard Error 1.12	7.8 letters Standard Error 1.11

SECONDARY outcome

Timeframe: Up to Week 72

Population: Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization.

BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision\^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores indicate improvement in VA. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA Over Time in Overall ITT Population Participants Gaining ≥ 0 Letters	98.9 percentage of participants	98.9 percentage of participants
Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA Over Time in Overall ITT Population Participants Gaining ≥ 5 Letters	94.6 percentage of participants	90.4 percentage of participants
Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA Over Time in Overall ITT Population Participants Gaining ≥ 10 Letters	76.3 percentage of participants	69.1 percentage of participants
Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA Over Time in Overall ITT Population Participants Gaining ≥ 15 Letters	49.5 percentage of participants	44.7 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 72

Population: Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization.

BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision\^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores indicate improvement in VA. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Percentage of Participants Losing ≥ 15, ≥ 10, or ≥ 5 Letters in BCVA Over Time in Overall ITT Population Participants Losing ≥ 5 Letters	19.4 percentage of participants	27.7 percentage of participants
Percentage of Participants Losing ≥ 15, ≥ 10, or ≥ 5 Letters in BCVA Over Time in Overall ITT Population Participants Losing ≥ 10 Letters	7.5 percentage of participants	11.7 percentage of participants
Percentage of Participants Losing ≥ 15, ≥ 10, or ≥ 5 Letters in BCVA Over Time in Overall ITT Population Participants Losing ≥ 15 Letters	4.3 percentage of participants	6.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision\^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 (Snellen equivalent \<20/800) to 100 (Snellen equivalent of 20/10) letters. Higher scores indicate improvement in VA. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Baseline	34.4 percentage of participants	31.9 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 1	53.4 percentage of participants	48.9 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 4	63.0 percentage of participants	53.3 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 8	67.0 percentage of participants	48.9 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 12	73.0 percentage of participants	56.5 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 16	69.7 percentage of participants	57.5 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 20	74.7 percentage of participants	67.0 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 24	70.6 percentage of participants	61.6 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 28	71.8 percentage of participants	63.2 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 32	78.8 percentage of participants	62.5 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 36	72.6 percentage of participants	62.7 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 40	78.4 percentage of participants	70.6 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 44	82.1 percentage of participants	67.1 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 48	80.9 percentage of participants	70.4 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 52	78.6 percentage of participants	64.2 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 56	82.1 percentage of participants	58.7 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 60	82.0 percentage of participants	68.8 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 64	82.5 percentage of participants	69.8 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 68	81.1 percentage of participants	71.4 percentage of participants
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time Week 72	82.7 percentage of participants	71.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision\^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 (Snellen equivalent \<20/800) to 100 (Snellen equivalent of 20/10) letters. Higher scores indicate improvement in VA. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 24	17.6 percentage of participants	8.1 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Baseline	0 percentage of participants	0 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 1	2.3 percentage of participants	0 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 4	6.5 percentage of participants	2.2 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 8	10.2 percentage of participants	5.6 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 12	10.1 percentage of participants	8.7 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 16	13.5 percentage of participants	6.9 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 20	14.5 percentage of participants	8.8 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 28	12.9 percentage of participants	11.5 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 32	17.5 percentage of participants	13.8 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 36	13.7 percentage of participants	12.0 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 40	12.2 percentage of participants	11.8 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 44	23.9 percentage of participants	8.9 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 48	23.5 percentage of participants	14.8 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 52	15.7 percentage of participants	7.4 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 56	14.9 percentage of participants	9.3 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 60	13.1 percentage of participants	9.4 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 64	19.3 percentage of participants	11.3 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 68	18.9 percentage of participants	10.2 percentage of participants
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time Week 72	11.5 percentage of participants	11.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision\^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 (Snellen equivalent \<20/800) to 100 (Snellen equivalent of 20/10) letters. Higher scores indicate improvement in VA. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Baseline	3.2 percentage of participants	4.3 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 1	2.3 percentage of participants	2.2 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 4	2.2 percentage of participants	3.3 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 8	2.3 percentage of participants	3.3 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 12	2.2 percentage of participants	2.2 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 16	1.1 percentage of participants	1.1 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 20	1.2 percentage of participants	2.2 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 24	2.4 percentage of participants	1.2 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 28	3.5 percentage of participants	2.3 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 32	2.5 percentage of participants	1.3 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 36	1.4 percentage of participants	1.2 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 40	2.7 percentage of participants	2.4 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 44	1.5 percentage of participants	1.3 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 48	0 percentage of participants	1.2 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 52	1.4 percentage of participants	0 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 56	3.0 percentage of participants	0 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 60	1.6 percentage of participants	1.6 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 64	1.8 percentage of participants	0 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 68	1.9 percentage of participants	0 percentage of participants
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time Week 72	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 44 and Week 48

CST was defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 millimetre (mm) central subfield. CST was measured using spectral domain optical coherence tomography (SD-OCT). Negative change from baseline values denotes improvement. This analysis used a MMRM model.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=61 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=63 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in Central Subfield Thickness (CST) Averaged Over Week 44 and Week 48 in Treatment-naïve Participants	-202.4 μm Standard Error 10.63	-192.4 μm Standard Error 10.11

SECONDARY outcome

Timeframe: Baseline, Week 44 and Week 48

CST was defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 mm central subfield. CST was measured using SD-OCT. Negative change from baseline values denotes improvement. This analysis used a MMRM model.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=32 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=31 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in CST Averaged Over Week 44 and Week 48 in Previously Treated Participants	-194.4 micrometre (μm) Standard Error 19.58	-171.2 micrometre (μm) Standard Error 18.79

SECONDARY outcome

Timeframe: Baseline, Week 44 and Week 48

Population: Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in CST Averaged Over Week 44 and Week 48 in Overall ITT Population	-201.6 μm Standard Error 8.33	-178.8 μm Standard Error 8.15

SECONDARY outcome

Timeframe: Baseline, Week 32 and Week 36

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=61 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=63 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in CST Averaged Over Week 32 and Week 36 in Treatment-naïve Participants	-197.9 μm Standard Error 10.26	-180.3 μm Standard Error 9.97

SECONDARY outcome

Timeframe: Baseline, Week 32 and Week 36

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=32 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=31 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in CST Averaged Over Week 32 and Week 36 in Previously Treated Participants	-177.2 μm Standard Error 18.38	-150.0 μm Standard Error 18.38

SECONDARY outcome

Timeframe: Baseline, Week 32 and Week 36

Population: Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline Averaged Over Week 32 and Week 36 in Overall ITT Population	-191.4 μm Standard Error 8.51	-172.1 μm Standard Error 8.38

SECONDARY outcome

Timeframe: Baseline, Week 20 and Week 24

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=61 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=63 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in CST Averaged Over Week 20 and Week 24 in Treatment-naïve Participants	-184.3 μm Standard Error 10.05	-169.7 μm Standard Error 9.89

SECONDARY outcome

Timeframe: Baseline, Week 20 and Week 24

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=32 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=31 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in CST Averaged Over Week 20 and Week 24 in Previously Treated Participants	-163.2 μm Standard Error 17.75	-120.2 μm Standard Error 17.65

SECONDARY outcome

Timeframe: Baseline, Week 20 and Week 24

Population: Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in CST Averaged Over Week 20 and Week 24 in Overall ITT Population	-176.1 μm Standard Error 9.89	-153.9 μm Standard Error 9.80

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 52	-172.7 μm Standard Error 12.92	-136.9 μm Standard Error 12.25
Change From Baseline in CST Over Time in Overall ITT Population Baseline	493.0 μm Standard Error 11.55	498.4 μm Standard Error 14.10
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 4	-121.0 μm Standard Error 9.82	-92.2 μm Standard Error 9.77
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 8	-138.9 μm Standard Error 9.67	-108.2 μm Standard Error 9.59
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 12	-147.9 μm Standard Error 9.63	-125.3 μm Standard Error 9.54
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 16	-158.6 μm Standard Error 10.28	-138.3 μm Standard Error 10.19
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 20	-172.8 μm Standard Error 10.11	-149.8 μm Standard Error 10.00
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 24	-174.1 μm Standard Error 10.12	-152.9 μm Standard Error 10.02
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 28	-181.1 μm Standard Error 10.53	-154.1 μm Standard Error 10.38
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 32	-186.4 μm Standard Error 8.87	-165.6 μm Standard Error 8.77
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 36	-191.1 μm Standard Error 9.58	-174.9 μm Standard Error 9.33
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 40	-193.4 μm Standard Error 8.92	-166.7 μm Standard Error 8.76
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 44	-197.3 μm Standard Error 8.95	-172.7 μm Standard Error 8.73
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 48	-200.1 μm Standard Error 9.04	-179.2 μm Standard Error 8.84
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 56	-173.8 μm Standard Error 11.43	-129.2 μm Standard Error 10.99
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 60	-155.5 μm Standard Error 13.18	-130.6 μm Standard Error 12.65
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 64	-161.4 μm Standard Error 13.65	-163.0 μm Standard Error 13.44
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 68	-160.1 μm Standard Error 11.26	-136.6 μm Standard Error 10.96
Change From Baseline in CST Over Time in Overall ITT Population Change at Week 72	-159.5 μm Standard Error 11.62	-154.3 μm Standard Error 11.55

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72

Absence of DME was defined as CST \< 325 μm for Spectralis SD-OCT, or \< 315 μm for Cirrus SD-OCT or Topcon SD-OCT. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Baseline	0 percentage of participants The 95% CI was not estimable due to an insufficient number of participants with events.	2.1 percentage of participants Interval 0.0 to 5.0
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 4	31.1 percentage of participants Interval 21.5 to 40.7	25.8 percentage of participants Interval 16.7 to 34.9
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 8	45.3 percentage of participants Interval 34.8 to 55.9	37.8 percentage of participants Interval 27.8 to 47.8
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 12	47.1 percentage of participants Interval 36.6 to 57.6	46.2 percentage of participants Interval 35.9 to 56.4
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 16	57.5 percentage of participants Interval 47.1 to 67.9	49.4 percentage of participants Interval 38.9 to 59.9
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 20	64.2 percentage of participants Interval 53.8 to 74.6	60.7 percentage of participants Interval 50.5 to 70.8
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 24	65.9 percentage of participants Interval 55.8 to 76.0	66.3 percentage of participants Interval 56.3 to 76.3
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 28	75.6 percentage of participants Interval 66.3 to 84.9	66.7 percentage of participants Interval 56.8 to 76.6
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 32	75.3 percentage of participants Interval 65.7 to 85.0	67.1 percentage of participants Interval 56.7 to 77.5
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 36	75.3 percentage of participants Interval 65.5 to 85.2	73.2 percentage of participants Interval 63.6 to 82.8
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 40	77.3 percentage of participants Interval 67.9 to 86.8	70.2 percentage of participants Interval 60.5 to 80.0
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 44	80.6 percentage of participants Interval 71.1 to 90.1	75.9 percentage of participants Interval 66.5 to 85.4
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 48	79.4 percentage of participants Interval 69.8 to 89.0	72.5 percentage of participants Interval 62.7 to 82.3
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 52	70.6 percentage of participants Interval 59.8 to 81.4	55.6 percentage of participants Interval 44.7 to 66.4
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 56	67.6 percentage of participants Interval 56.5 to 78.8	57.3 percentage of participants Interval 46.1 to 68.5
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 60	62.3 percentage of participants Interval 50.1 to 74.5	62.5 percentage of participants Interval 50.6 to 74.4
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 64	59.6 percentage of participants Interval 46.9 to 72.4	62.3 percentage of participants Interval 49.2 to 75.3
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 68	58.5 percentage of participants Interval 45.2 to 71.8	61.2 percentage of participants Interval 47.6 to 74.9
Percentage of Participants With Absence of DME Over Time in Overall ITT Population Week 72	61.5 percentage of participants Interval 48.3 to 74.8	62.2 percentage of participants Interval 48.1 to 76.4

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 12, 24, 36, 48, and 72

The absence of IRF in the study eye (defined as IRF absent or definite outside center subfield only) was assessed by the central reading center using SD-OCT. The percentage of participants with absence of IRF at foveal center are reported. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Percentage of Participants With Absence of Intraretinal Fluid (IRF) Over Time in Overall ITT Population Baseline	19.6 percentage of participants	22.3 percentage of participants
Percentage of Participants With Absence of Intraretinal Fluid (IRF) Over Time in Overall ITT Population Week 4	53.9 percentage of participants	47.8 percentage of participants
Percentage of Participants With Absence of Intraretinal Fluid (IRF) Over Time in Overall ITT Population Week 12	60.5 percentage of participants	51.1 percentage of participants
Percentage of Participants With Absence of Intraretinal Fluid (IRF) Over Time in Overall ITT Population Week 24	69.5 percentage of participants	69.8 percentage of participants
Percentage of Participants With Absence of Intraretinal Fluid (IRF) Over Time in Overall ITT Population Week 36	70.4 percentage of participants	71.1 percentage of participants
Percentage of Participants With Absence of Intraretinal Fluid (IRF) Over Time in Overall ITT Population Week 48	78.8 percentage of participants	78.2 percentage of participants
Percentage of Participants With Absence of Intraretinal Fluid (IRF) Over Time in Overall ITT Population Week 72	71.2 percentage of participants	75.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 12, 24, 36, 48, and 72

The absence of SRF in the study eye (defined as SRF absent or definite outside center subfield only) was assessed by the central reading center using SD-OCT. The percentage of participants with absence of SRF at the foveal center are reported. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Arm A: Vamikibart + Ranibizumab n=93 Participants Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 Participants Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Percentage of Participants With Absence of Subretinal Fluid (SRF) Over Time in Overall ITT Population Week 24	98.8 percentage of participants	96.5 percentage of participants
Percentage of Participants With Absence of Subretinal Fluid (SRF) Over Time in Overall ITT Population Baseline	60.4 percentage of participants	63.8 percentage of participants
Percentage of Participants With Absence of Subretinal Fluid (SRF) Over Time in Overall ITT Population Week 4	89.9 percentage of participants	82.2 percentage of participants
Percentage of Participants With Absence of Subretinal Fluid (SRF) Over Time in Overall ITT Population Week 12	98.9 percentage of participants	93.4 percentage of participants
Percentage of Participants With Absence of Subretinal Fluid (SRF) Over Time in Overall ITT Population Week 36	100 percentage of participants	96.4 percentage of participants
Percentage of Participants With Absence of Subretinal Fluid (SRF) Over Time in Overall ITT Population Week 48	98.5 percentage of participants	97.4 percentage of participants
Percentage of Participants With Absence of Subretinal Fluid (SRF) Over Time in Overall ITT Population Week 72	98.1 percentage of participants	100 percentage of participants

Adverse Events

Arm A: Vamikibart + Ranibizumab

Serious events: 22 serious events

Other events: 38 other events

Deaths: 1 deaths

Arm B: Ranibizumab

Serious events: 17 serious events

Other events: 48 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Arm A: Vamikibart + Ranibizumab n=93 participants at risk Participants received vamikibart, 1 mg as IVT injection, Q4W in combination with ranibizumab, 0.5 mg as IVT injection, Q4W up to Week 44 followed by an observational period up to Week 72.	Arm B: Ranibizumab n=94 participants at risk Participants received ranibizumab, 0.5 mg as an IVT injection, Q4W in combination with sham treatment up to Week 44 followed by an observational period up to Week 72.
Injury, poisoning and procedural complications Fall	1.1% 1/93 • Number of events 1 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.	5.3% 5/94 • Number of events 6 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.
Metabolism and nutrition disorders Diabetes mellitus	4.3% 4/93 • Number of events 4 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.	6.4% 6/94 • Number of events 6 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.
Vascular disorders Hypertension	7.5% 7/93 • Number of events 8 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.	9.6% 9/94 • Number of events 9 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.
Eye disorders Cataract	5.4% 5/93 • Number of events 7 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.	3.2% 3/94 • Number of events 3 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.
Eye disorders Conjunctival haemorrhage	8.6% 8/93 • Number of events 12 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.	8.5% 8/94 • Number of events 8 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.
Eye disorders Diabetic retinal oedema	9.7% 9/93 • Number of events 10 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.	17.0% 16/94 • Number of events 16 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.
Infections and infestations COVID-19	9.7% 9/93 • Number of events 10 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.	2.1% 2/94 • Number of events 2 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.
Infections and infestations Nasopharyngitis	2.2% 2/93 • Number of events 2 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.	7.4% 7/94 • Number of events 7 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.
Infections and infestations Urinary tract infection	3.2% 3/93 • Number of events 3 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.	8.5% 8/94 • Number of events 10 • Up to Week 72 Safety population included all participants randomized to study treatment and received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Ocular AEs displayed include both study eye and fellow eye.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

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