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    Clinical Trial Results:
    A Phase II, Multicenter, Randomized, Double Masked, Active Comparator-Controlled Study to Investigate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7200220 in Combination With Ranibizumab Administered Intravitreally in Patients With Diabetic Macular Edema

    Summary
    EudraCT number
    		 2021-004390-31
    Trial protocol
    		 PL  
    Global end of trial date
    01 Oct 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Oct 2025
    First version publication date
    23 Oct 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    BP43464
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05151744
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4058
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Oct 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Oct 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main purpose of this study was to investigate the effect of RO7200220 in combination with ranibizumab on best corrected visual acuity (BCVA) in participants with diabetic macular edema (DME).
    Protection of trial subjects
    All study participants were required to read and sign an Informed Consent Form (ICF).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    17 Dec 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 29
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    Spain: 3
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    Israel: 20
    Country: Number of subjects enrolled
    Korea, Republic of: 10
    Country: Number of subjects enrolled
    Poland: 12
    Country: Number of subjects enrolled
    United States: 102
    Worldwide total number of subjects
    187
    EEA total number of subjects
    15
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    115
    From 65 to 84 years
    71
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 187 participants with 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.

    Pre-assignment
    Screening details
    		 Participants were randomized in 1:1 ratio to Vamikibart + Ranibizumab arm and Ranibizumab arm.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm A: Vamikibart + Ranibizumab
    Arm description
    		 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 type
    		 Experimental

    Investigational medicinal product name
    Ranibizumab
    Investigational medicinal product code
    RO4893594
    Other name
    Lucentis
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    Ranibizumab, 0.5 mg, as an IVT injection, Q4W up to Week 44.

    Investigational medicinal product name
    Vamikibart
    Investigational medicinal product code
    RO7200220
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    Vamikibart, 1 mg, as IVT injection, Q4W up to Week 44.

    Arm title
    		 Arm B: Ranibizumab
    Arm description
    		 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.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Sham
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    Sham is a procedure that mimics an IVT injection and involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye.

    Investigational medicinal product name
    Ranibizumab
    Investigational medicinal product code
    RO4893594
    Other name
    Lucentis
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    Ranibizumab, 0.5 mg, as an IVT injection, Q4W up to Week 44.

    Number of subjects in period 1
    		Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Started
    93
    94
    Previously-treated ITT Population
    32 [1]
    31 [2]
    Treatment-naive ITT Population
    61 [3]
    63 [4]
    Completed
    64
    81
    Not completed
    29
    13
         Physician decision
    2
    1
         Consent withdrawn by subject
    6
    3
         Non-compliance with Study Drug
    -
    1
         Adverse Event
    6
    2
         Death
    1
    2
         Lost to follow-up
    2
    2
         Reason not Specified
    10
    -
         Need for Rescue Treatment
    -
    1
         Lack of efficacy
    1
    1
         Protocol deviation
    1
    -
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: 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.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: 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.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: 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.
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: 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.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm A: Vamikibart + Ranibizumab
    Reporting group description
    		 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.

    Reporting group title
    Arm B: Ranibizumab
    Reporting group description
    		 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.

    Reporting group values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab Total
    Number of subjects
    		 93 94 187
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 61.7 ( 10.1 ) 62.1 ( 9.3 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 31 39 70
        Male
    		 62 55 117
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 6 14 20
        Not Hispanic or Latino
    		 56 56 112
        Unknown or Not Reported
    		 31 24 55
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 7 3 10
        White
    		 45 60 105
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 41 31 72

    End points

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    End points reporting groups
    Reporting group title
    Arm A: Vamikibart + Ranibizumab
    Reporting group description
    		 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.

    Reporting group title
    Arm B: Ranibizumab
    Reporting group description
    		 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.

    Primary: Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged Over Week 44 and Week 48 in Treatment-naïve Participants

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    End point title
    		 Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged Over Week 44 and Week 48 in Treatment-naïve Participants
    End point description
    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. 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. This analysis used a Mixed Model for Repeated Measurements (MMRM) model. Adjusted mean has been reported here.
    End point type
    Primary
    End point timeframe
    Baseline, Week 44 and Week 48
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    61
    63
    Units: letters
        arithmetic mean (standard error)
    12.8 ( 1.30 )
    9.4 ( 1.25 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0625
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    3.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 7

    Secondary: Number of Participants With Systemic and Ocular Adverse Events (AEs)

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    End point title
    		 Number of Participants With Systemic and Ocular Adverse Events (AEs)
    End point description
    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. 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.
    End point type
    Secondary
    End point timeframe
    Up to Week 72
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: participants
        Systemic AEs
    54
    60
        Ocular AEs in Study Eyes
    33
    28
        Ocular AEs in Fellow Eyes
    25
    27
    No statistical analyses for this end point

    Secondary: Change From Baseline in BCVA Averaged Over Week 44 and Week 48 in Previously Treated Participants

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    End point title
    		 Change From Baseline in BCVA Averaged Over Week 44 and Week 48 in Previously Treated Participants
    End point description
    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. 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. This analysis used a MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 44 and Week 48
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    32
    31
    Units: letters
        arithmetic mean (standard error)
    11.1 ( 1.50 )
    8.4 ( 1.49 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2052
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    2.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 7

    Secondary: Change From Baseline in BCVA Averaged Over Week 44 and Week 48 in Overall ITT Population

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    End point title
    		 Change From Baseline in BCVA Averaged Over Week 44 and Week 48 in Overall ITT Population
    End point description
    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. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. This analysis used a MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 44 and Week 48
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: letters
        arithmetic mean (standard error)
    12.4 ( 0.99 )
    9.1 ( 0.96 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0192
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    3.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 6

    Secondary: Change From Baseline in BCVA Averaged Over Week 32 and Week 36 in Treatment-naïve Participants

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    End point title
    		 Change From Baseline in BCVA Averaged Over Week 32 and Week 36 in Treatment-naïve Participants
    End point description
    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. 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. This analysis used a MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 32 and Week 36
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    61
    63
    Units: letters
        arithmetic mean (standard error)
    11.8 ( 0.97 )
    9.3 ( 0.94 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0637
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    2.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 5.2

    Secondary: Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Previously Treated Participants

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    End point title
    		 Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Previously Treated Participants
    End point description
    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. 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. This analysis used a MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 32 and Week 36
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    32
    31
    Units: letters
        arithmetic mean (standard error)
    8.3 ( 1.43 )
    7.5 ( 1.46 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7091
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.3
         upper limit
    		 4.9

    Secondary: Change From Baseline in BCVA Averaged Over Week 20 and Week 24 in Treatment-naïve Participants

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    End point title
    		 Change From Baseline in BCVA Averaged Over Week 20 and Week 24 in Treatment-naïve Participants
    End point description
    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. 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. This analysis used a MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 20 and Week 24
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    61
    63
    Units: letters
        arithmetic mean (standard error)
    10.6 ( 1.04 )
    8.5 ( 1.01 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1498
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 5

    Secondary: Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Overall ITT Population

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    End point title
    		 Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Overall ITT Population
    End point description
    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. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. This analysis used a MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 32 and Week 36
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: letters
        arithmetic mean (standard error)
    10.6 ( 0.81 )
    8.7 ( 0.80 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1107
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 4.1

    Secondary: Change From Baseline in BCVA Averaged Over Week 20 and Week 24, in Overall ITT Population

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    End point title
    		 Change From Baseline in BCVA Averaged Over Week 20 and Week 24, in Overall ITT Population
    End point description
    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. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. This analysis used a MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 20 and Week 24
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: letters
        arithmetic mean (standard error)
    9.7 ( 0.84 )
    7.8 ( 0.83 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1036
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 4.3

    Secondary: Change From Baseline in BCVA Averaged Over Week 20 and Week 24 in Previously Treated Participants

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    End point title
    		 Change From Baseline in BCVA Averaged Over Week 20 and Week 24 in Previously Treated Participants
    End point description
    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. 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. This analysis used a MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 20 and Week 24
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    32
    31
    Units: letters
        arithmetic mean (standard error)
    8.1 ( 1.46 )
    6.2 ( 1.47 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3783
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 6

    Secondary: Change from Baseline in BCVA Over Time in Overall ITT Population

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    End point title
    		 Change from Baseline in BCVA Over Time in Overall ITT Population
    End point description
    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. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. This analysis used a MMRM model. Adjusted mean has been reported here. n = number of participants with data available for analysis at the specified timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: letters
    arithmetic mean (standard error)
        Baseline (n=93,94)
    62.6 ( 1.02 )
    62.0 ( 1.01 )
        Change at Week 4 (n=92,90)
    6.7 ( 0.64 )
    4.2 ( 0.65 )
        Change at Week 8 (n=88,90)
    7.6 ( 0.76 )
    4.6 ( 0.76 )
        Change at Week 12 (n=89,92)
    8.9 ( 0.78 )
    6.4 ( 0.78 )
        Change at Week 16 (n=89,87)
    9.3 ( 0.83 )
    7.4 ( 0.83 )
        Change at Week 20 (n=83,91)
    9.7 ( 0.81 )
    7.6 ( 0.80 )
        Change at Week 24 (n=85,86)
    9.8 ( 1.03 )
    8.0 ( 1.02 )
        Change at Week 28 (n=85,87)
    10.1 ( 0.87 )
    8.5 ( 0.87 )
        Change at Week 32 (n=80,80)
    10.5 ( 0.88 )
    8.8 ( 0.87 )
        Change at Week 36 (n=73,83)
    10.6 ( 0.84 )
    8.6 ( 0.83 )
        Change at Week 40 (n=74,85)
    10.9 ( 0.95 )
    8.8 ( 0.93 )
        Change at Week 44 (n=67,79)
    12.2 ( 1.01 )
    8.7 ( 0.99 )
        Change at Week 48 (n=68,81)
    12.5 ( 1.03 )
    9.4 ( 1.00 )
        Change at Week 52 (n=70,81)
    11.1 ( 1.07 )
    8.0 ( 1.03 )
        Change at Week 56 (n=67,75)
    10.8 ( 1.13 )
    7.8 ( 1.09 )
        Change at Week 60 (n=61,64)
    10.4 ( 1.18 )
    7.7 ( 1.14 )
        Change at Week 64 (n=57,53)
    10.2 ( 1.12 )
    8.2 ( 1.10 )
        Change at Week 68 (n=53,49)
    9.9 ( 1.14 )
    7.6 ( 1.11 )
        Change at Week 72 (n=52,45)
    9.2 ( 1.12 )
    7.8 ( 1.11 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA Over Time in Overall ITT Population

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    End point title
    		 Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA Over Time in Overall ITT Population
    End point description
    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. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. Percentages have been rounded off.
    End point type
    Secondary
    End point timeframe
    Up to Week 72
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: percentage of participants
    number (not applicable)
        Participants Gaining ≥ 0 Letters
    98.9
    98.9
        Participants Gaining ≥ 5 Letters
    94.6
    90.4
        Participants Gaining ≥ 10 Letters
    76.3
    69.1
        Participants Gaining ≥ 15 Letters
    49.5
    44.7
    No statistical analyses for this end point

    Secondary: Percentage of Participants Losing ≥ 15, ≥ 10, or ≥ 5 Letters in BCVA Over Time in Overall ITT Population

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    End point title
    		 Percentage of Participants Losing ≥ 15, ≥ 10, or ≥ 5 Letters in BCVA Over Time in Overall ITT Population
    End point description
    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. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. Percentages have been rounded off.
    End point type
    Secondary
    End point timeframe
    Up to Week 72
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: percentage of participants
    number (not applicable)
        Participants Losing ≥ 5 Letters
    19.4
    27.7
        Participants Losing ≥ 10 Letters
    7.5
    11.7
        Participants Losing ≥ 15 Letters
    4.3
    6.4
    No statistical analyses for this end point

    Secondary: Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time

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    End point title
    		 Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time
    End point description
    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. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. n = number of participants with data available for analysis at the specified timepoint. Percentages have been rounded off.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: percentage of participants
    number (not applicable)
        Baseline (n=93,94)
    34.4
    31.9
        Week 1 (n=88,90)
    53.4
    48.9
        Week 4 (n=92,90)
    63.0
    53.3
        Week 8 (n=88,90)
    67.0
    48.9
        Week 12 (n=89,92))
    73.0
    56.5
        Week 16 (n=89,87)
    69.7
    57.5
        Week 20 (n=83,91)
    74.7
    67.0
        Week 24 (n=85,86)
    70.6
    61.6
        Week 28 (n=85,87)
    71.8
    63.2
        Week 32 (n=80,80)
    78.8
    62.5
        Week 36 (n=73,83)
    72.6
    62.7
        Week 40 (n=74,85)
    78.4
    70.6
        Week 44 (n=67,79)
    82.1
    67.1
        Week 48 (n=68,81)
    80.9
    70.4
        Week 52 (n=70,81)
    78.6
    64.2
        Week 56 (n=67,75)
    82.1
    58.7
        Week 60 (n=61,64)
    82.0
    68.8
        Week 64 (n=57,53)
    82.5
    69.8
        Week 68 (n=53,49)
    81.1
    71.4
        Week 72 (n=52,45)
    82.7
    71.1
    No statistical analyses for this end point

    Secondary: Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time

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    End point title
    		 Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time
    End point description
    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. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. n = number of participants with data available for analysis at the specified timepoint. Percentages have been rounded off.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: percentage of participants
    number (not applicable)
        Baseline (n=93,94)
    0
    0
        Week 1 (n=88,90)
    2.3
    0
        Week 4 (n=92,90)
    6.5
    2.2
        Week 8 (n=88,90)
    10.2
    5.6
        Week 12 (n=89,92)
    10.1
    8.7
        Week 16 (n=89,87)
    13.5
    6.9
        Week 20 (n=83,91)
    14.5
    8.8
        Week 24 (n=85,86)
    17.6
    8.1
        Week 28 (n=85,87)
    12.9
    11.5
        Week 32 (n=80,80)
    17.5
    13.8
        Week 36 (n=73,83)
    13.7
    12.0
        Week 40 (n=74,85)
    12.2
    11.8
        Week 44 (n=67,79)
    23.9
    8.9
        Week 48 (n=68,81)
    23.5
    14.8
        Week 52 (n=70,81)
    15.7
    7.4
        Week 56 (n=67,75)
    14.9
    9.3
        Week 60 (n=61,64)
    13.1
    9.4
        Week 64 (n=57,53)
    19.3
    11.3
        Week 68 (n=53,49)
    18.9
    10.2
        Week 72 (n=52,45)
    11.5
    11.1
    No statistical analyses for this end point

    Secondary: Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time

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    End point title
    		 Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time
    End point description
    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. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. n = number of participants with data available for analysis at the specified timepoint. Percentages have been rounded off.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: percentage of participants
    number (not applicable)
        Baseline (n=93,94)
    3.2
    4.3
        Week 1 (n=88,90)
    2.3
    2.2
        Week 4 (n=92,90)
    2.2
    3.3
        Week 8 (n=88,90)
    2.3
    3.3
        Week 12 (n=89,92)
    2.2
    2.2
        Week 16 (n=89,87)
    1.1
    1.1
        Week 20 (n=83,91)
    1.2
    2.2
        Week 24 (n=85,86)
    2.4
    1.2
        Week 28 (n=85,87)
    3.5
    2.3
        Week 32 (n=80,80)
    2.5
    1.3
        Week 36 (n=73,83)
    1.4
    1.2
        Week 40 (n=74,85)
    2.7
    2.4
        Week 44 (n=67,79)
    1.5
    1.3
        Week 48 (n=68,81)
    0
    1.2
        Week 52 (n=70,81)
    1.4
    0
        Week 56 (n=67,75)
    3.0
    0
        Week 60 (n=61,64)
    1.6
    1.6
        Week 64 (n=57,53)
    1.8
    0
        Week 68 (n=53,49)
    1.9
    0
        Week 72 (n=52,45)
    0
    0
    No statistical analyses for this end point

    Secondary: Change From Baseline in CST Averaged Over Week 44 and Week 48 in Previously Treated Participants

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    End point title
    		 Change From Baseline in CST Averaged Over Week 44 and Week 48 in Previously Treated Participants
    End point description
    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. 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. This analysis used a MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 44 and Week 48
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    32
    31
    Units: micrometre (μm)
        arithmetic mean (standard error)
    -194.4 ( 19.58 )
    -171.2 ( 18.79 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3951
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    -23.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -76.8
         upper limit
    		 30.5

    Secondary: Change From Baseline in Central Subfield Thickness (CST) Averaged Over Week 44 and Week 48 in Treatment-naïve Participants

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    End point title
    		 Change From Baseline in Central Subfield Thickness (CST) Averaged Over Week 44 and Week 48 in Treatment-naïve Participants
    End point description
    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. 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. This analysis used a MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 44 and Week 48
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    61
    63
    Units: μm
        arithmetic mean (standard error)
    -202.4 ( 10.63 )
    -192.4 ( 10.11 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4968
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    -10
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -38.9
         upper limit
    		 18.9

    Secondary: Change From Baseline in CST Averaged Over Week 44 and Week 48 in Overall ITT Population

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    End point title
    		 Change From Baseline in CST Averaged Over Week 44 and Week 48 in Overall ITT Population
    End point description
    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. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. This analysis used an MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 44 and Week 48
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: μm
        arithmetic mean (standard error)
    -201.6 ( 8.33 )
    -178.8 ( 8.15 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0521
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    -22.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -45.8
         upper limit
    		 0.2

    Secondary: Change From Baseline in CST Averaged Over Week 32 and Week 36 in Previously Treated Participants

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    End point title
    		 Change From Baseline in CST Averaged Over Week 32 and Week 36 in Previously Treated Participants
    End point description
    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. 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. This analysis used an MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 32 and Week 36
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    32
    31
    Units: μm
        arithmetic mean (standard error)
    -177.2 ( 18.38 )
    -150.0 ( 18.38 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2972
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    -27.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -78.6
         upper limit
    		 24.2

    Secondary: Change From Baseline in CST Averaged Over Week 32 and Week 36 in Treatment-naïve Participants

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    End point title
    		 Change From Baseline in CST Averaged Over Week 32 and Week 36 in Treatment-naïve Participants
    End point description
    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. 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. This analysis used an MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 32 and Week 36
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    61
    63
    Units: μm
        arithmetic mean (standard error)
    -197.9 ( 10.26 )
    -180.3 ( 9.97 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2227
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    -17.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -45.7
         upper limit
    		 10.7

    Secondary: Change From Baseline in CST Averaged Over Week 20 and Week 24 in Treatment-naïve Participants

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    End point title
    		 Change From Baseline in CST Averaged Over Week 20 and Week 24 in Treatment-naïve Participants
    End point description
    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. 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. This analysis used an MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 20 and Week 24
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    61
    63
    Units: μm
        arithmetic mean (standard error)
    -184.3 ( 10.05 )
    -169.7 ( 9.89 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.303
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    -14.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -42.4
         upper limit
    		 13.2

    Secondary: Change From Baseline Averaged Over Week 32 and Week 36 in Overall ITT Population

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    End point title
    		 Change From Baseline Averaged Over Week 32 and Week 36 in Overall ITT Population
    End point description
    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. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. This analysis used an MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 32 and Week 36
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: μm
        arithmetic mean (standard error)
    -191.4 ( 8.51 )
    -172.1 ( 8.38 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1071
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    -19.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -42.9
         upper limit
    		 4.2

    Secondary: Change From Baseline in CST Averaged Over Week 20 and Week 24 in Previously Treated Participants

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    End point title
    		 Change From Baseline in CST Averaged Over Week 20 and Week 24 in Previously Treated Participants
    End point description
    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. 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. This analysis used an MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 20 and Week 24
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    32
    31
    Units: μm
        arithmetic mean (standard error)
    -163.2 ( 17.75 )
    -120.2 ( 17.65 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0878
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    -43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -92.4
         upper limit
    		 6.4

    Secondary: Change From Baseline in CST Averaged Over Week 20 and Week 24 in Overall ITT Population

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    End point title
    		 Change From Baseline in CST Averaged Over Week 20 and Week 24 in Overall ITT Population
    End point description
    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. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. This analysis used an MMRM model. Adjusted mean has been reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 20 and Week 24
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: μm
        arithmetic mean (standard error)
    -176.1 ( 9.89 )
    -153.9 ( 9.80 )
    Statistical analysis title
    		 Arm A vs Arm B
    Comparison groups
    Arm A: Vamikibart + Ranibizumab v Arm B: Ranibizumab
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1111
    Method
    		 MMRM
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    -22.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -49.8
         upper limit
    		 5.2

    Secondary: Change From Baseline in CST Over Time in Overall ITT Population

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    End point title
    		 Change From Baseline in CST Over Time in Overall ITT Population
    End point description
    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. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. This analysis used an MMRM model. Adjusted mean has been reported here. n = number of participants with data available for analysis at the specified timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: μm
    arithmetic mean (standard error)
        Baseline (n=92,94)
    493.0 ( 11.55 )
    498.4 ( 14.10 )
        Change at Week 4 (n=90,89)
    -121.0 ( 9.82 )
    -92.2 ( 9.77 )
        Change at Week 8 (n=86,90)
    -138.9 ( 9.67 )
    -108.2 ( 9.59 )
        Change at Week 12 (n=87,91)
    -147.9 ( 9.63 )
    -125.3 ( 9.54 )
        Change at Week 16 (n=87,87)
    -158.6 ( 10.28 )
    -138.3 ( 10.19 )
        Change at Week 20 (n=81,89)
    -172.8 ( 10.11 )
    -149.8 ( 10.00 )
        Change at Week 24 (n=85,86)
    -174.1 ( 10.12 )
    -152.9 ( 10.02 )
        Change at Week 28 (n=82,87)
    -181.1 ( 10.53 )
    -154.1 ( 10.38 )
        Change at Week 32 (n=77,79)
    -186.4 ( 8.87 )
    -165.6 ( 8.77 )
        Change at Week 36 (n=73,82)
    -191.1 ( 9.58 )
    -174.9 ( 9.33 )
        Change at Week 40 (n=75,84)
    -193.4 ( 8.92 )
    -166.7 ( 8.76 )
        Change at Week 44 (n=67,79)
    -197.3 ( 8.95 )
    -172.7 ( 8.73 )
        Change at Week 48 (n=68,80)
    -200.1 ( 9.04 )
    -179.2 ( 8.84 )
        Change at Week 52 (n=68,81)
    -172.7 ( 12.92 )
    -136.9 ( 12.25 )
        Change at Week 56 (n=68,75)
    -173.8 ( 11.43 )
    -129.2 ( 10.99 )
        Change at Week 60 (n=61,64)
    -155.5 ( 13.18 )
    -130.6 ( 12.65 )
        Change at Week 64 (n=57,53)
    -161.4 ( 13.65 )
    -163.0 ( 13.44 )
        Change at Week 68 (n=53,49)
    -160.1 ( 11.26 )
    -136.6 ( 10.96 )
        Change at Week 72 (n=52,45)
    -159.5 ( 11.62 )
    -154.3 ( 11.55 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Absence of DME Over Time in Overall ITT Population

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    End point title
    		 Percentage of Participants With Absence of DME Over Time in Overall ITT Population
    End point description
    Absence of DME was defined as CST < 325 μm for Spectralis SD-OCT, or < 315 μm for Cirrus SD-OCT or Topcon SD-OCT. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. Percentages have been rounded off. n = number of participants with data available for analysis at the specified timepoint. -0.999 & 9999 = The 95% CI was not estimable due to an insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12, 16, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: percentage of participants
    number (confidence interval 95%)
        Baseline (n=92,94)
    0 (-0.999 to 9999)
    2.1 (0.0 to 5.0)
        Week 4 (n=90,89)
    31.1 (21.5 to 40.7)
    25.8 (16.7 to 34.9)
        Week 8 (n=86,90)
    45.3 (34.8 to 55.9)
    37.8 (27.8 to 47.8)
        Week 12 (n=87,91)
    47.1 (36.6 to 57.6)
    46.2 (35.9 to 56.4)
        Week 16 (n=87,87)
    57.5 (47.1 to 67.9)
    49.4 (38.9 to 59.9)
        Week 20 (n=81,89)
    64.2 (53.8 to 74.6)
    60.7 (50.5 to 70.8)
        Week 24 (n=85,86)
    65.9 (55.8 to 76.0)
    66.3 (56.3 to 76.3)
        Week 28 (n=82,87)
    75.6 (66.3 to 84.9)
    66.7 (56.8 to 76.6)
        Week 32 (n=77,79)
    75.3 (65.7 to 85.0)
    67.1 (56.7 to 77.5)
        Week 36 (n=73,82)
    75.3 (65.5 to 85.2)
    73.2 (63.6 to 82.8)
        Week 40 (n=75,84)
    77.3 (67.9 to 86.8)
    70.2 (60.5 to 80.0)
        Week 44 (n=67,79)
    80.6 (71.1 to 90.1)
    75.9 (66.5 to 85.4)
        Week 48 (n=68,80)
    79.4 (69.8 to 89.0)
    72.5 (62.7 to 82.3)
        Week 52 (n=68,81)
    70.6 (59.8 to 81.4)
    55.6 (44.7 to 66.4)
        Week 56 (n=68,75)
    67.6 (56.5 to 78.8)
    57.3 (46.1 to 68.5)
        Week 60 (n=61,64)
    62.3 (50.1 to 74.5)
    62.5 (50.6 to 74.4)
        Week 64 (n=57,53)
    59.6 (46.9 to 72.4)
    62.3 (49.2 to 75.3)
        Week 68 (n=53,49)
    58.5 (45.2 to 71.8)
    61.2 (47.6 to 74.9)
        Week 72 (n=52,45)
    61.5 (48.3 to 74.8)
    62.2 (48.1 to 76.4)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Absence of Intraretinal Fluid (IRF) Over Time in Overall ITT Population

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    End point title
    		 Percentage of Participants With Absence of Intraretinal Fluid (IRF) Over Time in Overall ITT Population
    End point description
    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. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. Percentages have been rounded off. n = number of participants with data available for analysis at the specified timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 12, 24, 36, 48, and 72
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: percentage of participants
    number (not applicable)
        Baseline (n=92,94)
    19.6
    22.3
        Week 4 (n=89,90)
    53.9
    47.8
        Week 12 (n=86,92)
    60.5
    51.1
        Week 24 (n=82,86)
    69.5
    69.8
        Week 36 (n=71,83)
    70.4
    71.1
        Week 48 (n=66,78)
    78.8
    78.2
        Week 72 (n=52,45)
    71.2
    75.6
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Absence of Subretinal Fluid (SRF) Over Time in Overall ITT Population

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    End point title
    		 Percentage of Participants With Absence of Subretinal Fluid (SRF) Over Time in Overall ITT Population
    End point description
    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 foveal center are reported. Overall ITT population included all randomized participants grouped according to the treatment assigned at randomization. Percentages have been rounded off. n = number of participants with data available for analysis at the specified timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 12, 24, 36, 48, and 72
    End point values
    		 Arm A: Vamikibart + Ranibizumab Arm B: Ranibizumab
    Number of subjects analysed
    93
    94
    Units: percentage of participants
    number (not applicable)
        Baseline (n=91,94)
    60.4
    63.8
        Week 4 (n= 89,90)
    89.9
    82.2
        Week 12 (n=87,91)
    98.9
    93.4
        Week 24 (n=82,86)
    98.8
    96.5
        Week 36 (n=72,83)
    100
    96.4
        Week 48 (n=66,78)
    98.5
    97.4
        Week 72 (n=52,45)
    98.1
    100
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to Week 72
    Adverse event reporting additional description
    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.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.1
    Reporting groups
    Reporting group title
    Arm B: Ranibizumab
    Reporting group description
    		 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.

    Reporting group title
    Arm A: Vamikibart + Ranibizumab
    Reporting group description
    		 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.

    Serious adverse events
    		 Arm B: Ranibizumab Arm A: Vamikibart + Ranibizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    17 / 94 (18.09%)
    22 / 93 (23.66%)
         number of deaths (all causes)
    2
    1
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    2 / 94 (2.13%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    2 / 94 (2.13%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Peripheral swelling
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain death
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Reproductive system and breast disorders
    Erectile dysfunction
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    2 / 94 (2.13%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Back injury
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture displacement
         subjects affected / exposed
    2 / 94 (2.13%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 94 (0.00%)
    2 / 93 (2.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Coronary artery disease
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nervous system disorders
    Ischaemic stroke
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 94 (0.00%)
    3 / 93 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    2 / 94 (2.13%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Vitritis
         subjects affected / exposed
    0 / 94 (0.00%)
    2 / 93 (2.15%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal occlusive vasculitis
         subjects affected / exposed
    0 / 94 (0.00%)
    2 / 93 (2.15%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ocular hypertension
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iritis
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye inflammation
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cataract subcapsular
         subjects affected / exposed
    1 / 94 (1.06%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic retinal oedema
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diabetic gastropathy
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephropathy
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    0 / 94 (0.00%)
    2 / 93 (2.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Soft tissue infection
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes ophthalmic
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endophthalmitis
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 93 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis acute
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypoglycaemia
         subjects affected / exposed
    2 / 94 (2.13%)
    0 / 93 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Arm B: Ranibizumab Arm A: Vamikibart + Ranibizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    48 / 94 (51.06%)
    38 / 93 (40.86%)
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    5 / 94 (5.32%)
    1 / 93 (1.08%)
         occurrences all number
    6
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    9 / 94 (9.57%)
    7 / 93 (7.53%)
         occurrences all number
    9
    8
    Eye disorders
    Cataract
         subjects affected / exposed
    3 / 94 (3.19%)
    5 / 93 (5.38%)
         occurrences all number
    3
    7
    Conjunctival haemorrhage
         subjects affected / exposed
    8 / 94 (8.51%)
    8 / 93 (8.60%)
         occurrences all number
    8
    12
    Diabetic retinal oedema
         subjects affected / exposed
    16 / 94 (17.02%)
    9 / 93 (9.68%)
         occurrences all number
    16
    10
    Infections and infestations
    COVID-19
         subjects affected / exposed
    2 / 94 (2.13%)
    9 / 93 (9.68%)
         occurrences all number
    2
    10
    Urinary tract infection
         subjects affected / exposed
    8 / 94 (8.51%)
    3 / 93 (3.23%)
         occurrences all number
    10
    3
    Nasopharyngitis
         subjects affected / exposed
    7 / 94 (7.45%)
    2 / 93 (2.15%)
         occurrences all number
    7
    2
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    6 / 94 (6.38%)
    4 / 93 (4.30%)
         occurrences all number
    6
    4

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Jul 2022
    1. Vamikibart administration was extended from Week 24 to Week 48, supported by the availability of new toxicology data (the 24-week off-treatment observation period was maintained). The objectives and endpoints (including the primary endpoint), schedule of activities, and anticipated study duration were updated to reflect the extended dosing. 2. The role of masked assessors was clarified 3. Participants previously treated with faricimab could now be enrolled after an appropriate washout period.
    23 Apr 2023
    The protocol was amended to update the information on clinical studies on RO7200220, benefit/risk assessment, exclusion criteria and safety assessment.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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