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Susvimo

Phase 3

Diabetic Macular Edema | Small molecule | Ophthalmology |Roche Holding AG|Last Updated: Aug 31, 2026

Target and mechanism

ModalitySmall molecule

Also known as Ranibizumab refill exchange

Success Probability

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Market & Valuation

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Trial Design

RandomizedACTIVE_CONTROLLED
Total Trials1
Total Enrollment672

FDA Designations

No designations recorded

Clinical trial landscape

Susvimo · 3 trials · 3 indications

Phase 3 3
NCT04503551A Multicenter, Randomized Study in Participants With Diabetic Retinopathy Without Center-involved Diabetic Macular Edema To Evaluate the Efficacy, Safety, and Pharmacokinetics of Ranibizumab Delivered Via the Port Delivery System Relative to the Comparator ArmDiabetic Retinopathy
COMPLETED174 Analytics
NCT04108156A Study to Evaluate Efficacy, Safety & Pharmacokinetics of the Port Delivery System (PDS) With Ranibizumab in Participants With Diabetic Macular Edema (DME) Compared With Intravitreal Ranibizumab; A Substudy to Evaluate the Safety of Re-implanting the PDS With Ranibizumab in Participants With DMEDiabetic Macular Edema
ACTIVE NOT_RECRUITING672 Analytics
NCT03683251Extension Study for the Port Delivery System With Ranibizumab (Portal)Neovascular Age-Related Macular Degeneration
RECRUITING1,000 Analytics
PHASE3COMPLETED
A Multicenter, Randomized Study in Participants With Diabetic Retinopathy Without Center-involved Diabetic Macular Edema To Evaluate the Efficacy, Safety, and Pharmacokinetics of Ranibizumab Delivered Via the Port Delivery System Relative to the Comparator Arm
Diabetic RetinopathyUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
A Study to Evaluate Efficacy, Safety & Pharmacokinetics of the Port Delivery System (PDS) With Ranibizumab in Participants With Diabetic Macular Edema (DME) Compared With Intravitreal Ranibizumab; A Substudy to Evaluate the Safety of Re-implanting the PDS With Ranibizumab in Participants With DME
Diabetic Macular EdemaUnlock trial analytics
PHASE3RECRUITING
Extension Study for the Port Delivery System With Ranibizumab (Portal)
Neovascular Age-Related Macular DegenerationUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage of Participants With a ≥2-Step Improvement From Baseline on the Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale (ETDRS-DRSS) at Week 52
Baseline, Week 52

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

Change in BCVA Score From Baseline Averaged Over Weeks 60 and 64 as Measured Using the ETDRS Chart in the Efficacy Population Using a Treatment Policy Strategy for all Intercurrent Events
Baseline to Week 64

BCVA = Best-Corrected Visual Acuity ETDRS = Early Treatment Diabetic Retinopathy Study A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.

Substudy: Number of Participants With Ocular and Systemic (Non-ocular) Adverse Events (AEs) and Severity of Ocular and Systemic AEs
Baseline to Week 72
Substudy: Number of Participants With Adverse Events of Special Interests (AESIs) and Severity of AESIs
Baseline to Week 72
Substudy: Duration of AESIs
Baseline to Week 72
Substudy: Number of Participants With Ocular AESIs and Severity of Ocular AESIs During the Post-operative Period
Up to Day 37 post re-implantation
Substudy: Number of Participants With Ocular AESIs and Severity of Ocular AESIs During the Follow-up Period
> 37 days post-implantation (up to approximately 72 weeks)
Substudy: Duration of Ocular AESIs During the Post-operative Period
Up to Day 37 post re-implantation
Substudy: Duration of Ocular AESIs During the Follow-up Period
> 37 days post-implantation (up to approximately 72 weeks)
Substudy: Number of Participants With Adverse Device Effects (ADEs) and Severity of ADEs
Baseline to Week 72
Substudy: Number of Participants With Anticipated Serious ADEs
Baseline to Week 72
Substudy: Duration of Serious ADEs
Baseline to Week 72
Substudy: Number of Device Deficiencies
Baseline to Week 72
Incidence and Severity of Ocular and Systemic (Non-Ocular) Adverse Events (AEs)
Baseline up to Week 240
Incidence, Severity, and Duration of Adverse Event of Special Interest (AESIs)
Baseline up to Week 240
Incidence, Severity, and Duration of PDS-Associated Ocular AESIs During the Postoperative Period (Up to 37 days of Initial Implantation) and Follow-Up Period (>37 days After Implantation Surgery) for Participants who Receive the PDS Implant in the Study
Baseline up to Week 240
Incidence and Severity of Adverse Device Effects
Baseline up to Week 240
Incidence, Causality, Severity, And Duration Of Anticipated Serious Adverse Device Effects
Baseline up to Week 240
Sub-study 1: Rate of Vitreous Hemorrhage Secondary to Choroidal Bleeding That Does not Resolve by the Week 4 Visit After Implant Insertion Surgery.
Baseline to Week 4
Sub-study 2: Number of Participants with Ocular and Systemic (Non-ocular) Adverse Events (AEs) and Severity of These AEs
Baseline to Week 72
Sub-study 2: Number of Participants with Adverse Events of Special Interests (AESIs) and Severity of AESIs
Baseline to Week 72
Sub-study 2: Duration of AESIs
Baseline to Week 72
Sub-study 2: Number of participants with Ocular AESIs and Severity of Ocular AESIs During the Post-operative Period
Up to Day 37 post re-implantation
Sub-study 2: Number of participants with Ocular AESIs and Severity of Ocular AESIs During the Follow-up Period
> 37 days post re-implantation (up to approximately Week 72)
Sub-study 2: Duration of Ocular AESIs During the Post-operative Period
Up to Day 37 post re-implantation
Sub-study 2: Duration of Ocular AESIs During the Follow-up Period
> 37 days post re-implantation (up to approximately Week 72)
Sub-study 2: Number of Participants with Adverse Device Effects (ADEs) and Severity of ADEs
Baseline to Week 72
Sub-study 2: Number of Participants with Anticipated Serious ADEs and Severity of Anticipated Serious ADEs
Baseline to Week 72
Sub-study 2: Duration of Anticipated Serious ADEs
Baseline to Week 72
Sub-study 2: Number of Device Deficiencies
Baseline to Week 72

Secondary Endpoints

Rate of Participants Developing a Vision-Threatening Complication or Center-involved Diabetic Macular Edema (CI-DME) Through Week 52
From Baseline through Week 52
Rate of Participants Developing PDR or ASNV Through Week 52
From Baseline through Week 52
Rate of Participants Developing CI-DME Through Week 52
From Baseline through Week 52
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Study Design & Arms

AllocationRANDOMIZED
MaskingSINGLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
PDS ArmEXPERIMENTALParticipants randomized to the PDS arm will receive two intravitreal ranibizumab injections and will then have the PDS implant (pre-filled with ranibizumab) surgically inserted. PDS implant refill-exchange procedures will be performed on a fixed interval every 36-weeks (Q36W) thereafter
Comparator ArmOTHERParticipants randomized to the comparator arm will undergo study visits every 4 weeks (Q4W) for comprehensive clinical monitoring until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q36W thereafter. Participants will be eligible to receive intravitreal ranibizumab 0.5 mg injections if treatment eligibility criteria are met.
Intravitreal ArmACTIVE_COMPARATORParticipants randomized to the intravitreal arm will receive IVT ranibizumab injection Q4W until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q24W thereafter.
Substudy: Cohort 1EXPERIMENTALParticipants will undergo re-implantation with the updated PDS implant (pre-filled with ranibizumab 100 milligrams per milliliter \[mg/mL\]) on Day 1 (or enrollment visit) and then will have two refill-exchanges (ranibizumab 100 mg/mL) Q24W up to 48 weeks.
Substudy: Cohort 2aEXPERIMENTALParticipants who received an updated PDS implant, have \< 24 weeks post-re-implantation follow-up and no scheduled refill-exchange visit in the main study, will undergo two refill-exchange procedures (ranibizumab 100 mg/mL) Q24W, post main study re-implantation visit.
Substudy: Cohort 2bEXPERIMENTALParticipants who received an updated PDS implant, have \< 48 weeks post-re-implantation follow-up and one refill exchange visit in the main study, regardless of whether the refill exchange was administered or the visit was missed, will undergo one refill-exchange procedure (ranibizumab 100 mg/mL) Q24W, post main study re-implantation visit.
PDS Implant Cohort 1 (US only)EXPERIMENTALParticipants with PDS implant from Study GX28228 treated with refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 168 to Week 240. Eligible participants from Study GX28228 will be enrolled upon completion of their final visit.
PDS Implant Cohort 2 (US only)EXPERIMENTALParticipants with PDS implant from Study GR40548 treated with refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 144 to Week 240. Eligible participants from Study GR40548 will be enrolled upon completion of their final visit.
PDS Implant Cohort 3 (US only)EXPERIMENTALParticipants in the intravitreal ranibizumab arm of Study GX28228 who will receive the PDS implant upon study entry and refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 168 to Week 240. Eligible participants from Study GX28228 will be enrolled upon completion of their final visit.
PDS Implant Cohort 4 (US only)EXPERIMENTALParticipants in the intravitreal ranibizumab arm of Study GR40548 who will receive the PDS implant upon study entry and refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 144 to Week 240. Eligible participants from Study GR40548 will be enrolled upon completion of their final visit.
PDS Implant Cohort 5 (ex-US only)EXPERIMENTALParticipants from Study WR42221 who completed Week 24 but were not eligible to be randomized within WR42221 and who will be treated with refill-exchanges of ranibizumab 100 mg/mL Q24W. Participants will be in the study for a minimum of 144 weeks and may continue after Week 144 until the PDS has received Health Authority approval (or non-approval) in their respective country and/or until the decision to close the study has been made by the sponsor.
PDS Implant Cohort 6 (ex-US only)EXPERIMENTALParticipants from Study WR42221 randomized to the Q24W arm, who will continue to be treated with refill-exchanges of ranibizumab 100 mg/mL Q24W. Participants will be in the study for a minimum of 144 weeks and may continue after Week 144 until the PDS has received Health Authority approval (or non-approval) in their respective country and/or until the decision to close the study has been made by the sponsor.
PDS Implant Cohort 7 (ex-US only)EXPERIMENTALParticipants from Study WR42221 randomized to the Q36W arm, who will continue to be treated with refill-exchanges of ranibizumab 100 mg/mL Q36W. Participants will be in the study for a minimum of 144 weeks and may continue after Week 144 until the PDS has received Health Authority approval (or non-approval) in their respective country and/or until the decision to close the study has been made by the sponsor.
Sub-study 1: PDS ImplantEXPERIMENTALParticipants will receive PDS implant using TPC on Day 1 followed by refill-exchanges of ranibizumab 100 mg/mL via the PDS Q24W.
Sub-study 2: Cohort 1EXPERIMENTALParticipants will undergo re-implantation with the updated PDS implant and receive 2 refill-exchanges of ranibizumab 100 mg/mL Q24W.
Sub-study 2: Cohort 2aEXPERIMENTALParticipants who received an updated PDS implant, have \< 24 weeks post-re-implantation follow-up and no refill exchange visit in the main study, will undergo two refill-exchange procedures with ranibizumab 100 mg/mL Q24W post main study re-implantation visit.
Sub-study 2: Cohort 2bEXPERIMENTALParticipants who received an updated PDS implant, have \< 48 weeks post-re-implantation follow-up and one refill exchange visit in the main study, will undergo one refill-exchange procedure with ranibizumab 100 mg/mL Q24W post main study re-implantation visit.

Interventions

NameTypeDescription
PDS Implant Pre-Filled with 100 mg/mL RanibizumabDRUGWill be administered as per the schedule described in individual arm.
Intravitreal Ranibizumab 0.5 mg InjectionDRUGWill be administered as per the schedule described in individual arm.
Ranibizumab refill exchangeDRUGWill be administered as per the schedule described in individual arm.
PDS Implant with Ranibizumab 100 mg/mLDRUGWill be administered as per the schedule described in individual arm
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites65

Inclusion Criteria: * Age ≥18 years at time of signing Informed Consent Form * Documented diagnosis of diabetes mellitus (Type 1 or Type 2) * HbA1c level of ≤12% within 2 months prior to screening or at screening Inclusion Criteria for Study Eye * Moderately severe or severe NPDR (ETDRS-DRSS leve...

Countries:United StatesPuerto RicoArgentinaAustraliaAustriaBelgiumBrazilFranceGermanyIsraelItalySpainSwitzerlandTaiwanTurkey (Türkiye)United Kingdom
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Recent Changes (Last 90 Days)

LOWAug 31, 2026NCT03683251lastUpdatePostDate: changed
LOWAug 31, 2026NCT03683251lastUpdatePostDate: changed
LOWAug 1, 2026NCT03683251lastUpdatePostDate: changed
LOWAug 1, 2026NCT03683251lastUpdatePostDate: changed
LOWAug 1, 2026NCT03683251lastUpdatePostDate: changed