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

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

Study BP43464 is a phase II, multicenter, randomized, double-masked active comparator-controlled study designed to assess the efficacy, safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of vamikibart in combination with, anti-vascular endothelial growth factor (VEGF) inhibitor, ranibizumab compared with ranibizumab alone in participants with diabetic macular edema. Only one eye will be chosen as the study eye. The duration of the study will be 76 weeks.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: Ranibizumab; Other: Sham Procedure; Drug: Vamikibart

• Study Type: Interventional
• Enrollment (Actual): 187
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1015ABO
    • Organización Médica de Investigación
  • Capital Federal, Argentina, C1120AAN
    • Oftalmos
  • Capital Federal, Argentina, C1116
    • Centro Oftalmologico Dr. Charles S.A.
  • Ciudad Autonoma Buenos Aires, Argentina, C1061AAE
    • Buenos Aires Mácula
  • Rosario, Argentina, S2000DLA
    • Grupo Laser Vision
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K2B 7E9
      • Retina Institute of Ottawa
    • Toronto, Ontario, Canada, M3C 0G9
      • Toronto Retina Institute
  • Quebec
    • Boisbriand, Quebec, Canada, J7H 0E8
      • Institut De L'Oeil Des Laurentides
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah MC
  • Petah Tikva, Israel, 4941492
    • Rabin MC
  • Rehovot, Israel, 7660101
    • Kaplan Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky MC
• Poland
  • Gliwice, Poland, 44-100
    • Niepubliczny Zak?ad Opieki Zdrowotnej PRYZMAT-OKULISTYKA
  • Krakow, Poland, 31-070
    • Centrum Medyczne UNO-MED
  • Olsztyn, Poland, 10-424
    • Centrum Diagnostyki i Mikrochirurgii Oka LENS
  • Tarnowskie Góry, Poland, 42-600
    • Caminomed
• Puerto Rico
  • Arecibo, Puerto Rico, 00613
    • Emanuelli Research and Development Center LLC
• South Korea
  • Busan, South Korea, 49241
    • Pusan National University Hospital
  • Daegu, South Korea, 42415
    • Yeungnam University Medical Center
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 07301
    • Kim's Eye Hospital
• Spain
  • Madrid, Spain, 28027
    • Clinica Universitaria De Navarra
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universitaria De Navarra
• United Kingdom
  • Gloucestershire, United Kingdom, GL1 3NN
    • Gloucestershire Hospitals NHS Foundation Trust
  • Guildford, United Kingdom, GU2 7XX
    • Royal Surrey County Hospital
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital NHS Foundation Trust
• United States
  • California
    • Arcadia, California, United States, 91006
      • Win Retina
    • Torrance, California, United States, 90502
      • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
    • Walnut Creek, California, United States, 94598
      • Bay Area Retina Associates
  • Florida
    • Melbourne, Florida, United States, 30394-7344
      • Florida Eye Associates
    • Tampa, Florida, United States, 33617
      • Retina Vitreous Associates of Florida
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants
  • Mississippi
    • Southaven, Mississippi, United States, 38671
      • Deep Blue Retina PLLC
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Verum Research LLC
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Retina Associates
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of diabetes mellitus (Type 1 or Type 2)
• Macular thickening secondary to diabetic macular edema (DME) involving the center of the macula
• Decreased visual acuity attributable primarily to DME
• Ability and willingness to provide written informed consent and to comply with the study protocol
• Willingness to allow Aqueous Humor collection
• For women of childbearing potential: agreement to remain abstinent or use at least one highly effective contraceptive method that results in a failure rate of <1% per year during the treatment period and for at least 12 weeks after the final dose of study treatment

Exclusion Criteria:

• Hemoglobin A1c (HbA1c) of greater than (>) 12%
• Uncontrolled blood pressure, defined as a systolic value greater than (>)180 millimeters of mercury (mmHg) and/or a diastolic value >100 mmHg while a patient is at rest
• Currently pregnant or breastfeeding, or intend to become pregnant during the study
• Prior treatment with panretinal photocoagulation or macular laser to the study eye
• Any intraocular or periocular corticosteroid treatment within the past 16 weeks prior to Day 1 to the study eye
• Prior Iluvien or Retisert implants within 3 years prior to Day 1 to the study eye
• Prior or concomitant treatment with anti-VEGF therapy within 8 weeks prior to Day 1 to the study eye; Vabysmo^TM within 16 weeks prior to Day 1, prior Beovu® is not permitted
• Prior administration of IVT brolucizumab (Beovu®): ever; vamikibart: </=24 weeks prior to Day 1) in either eye
• Any proliferative diabetic retinopathy
• Active intraocular or periocular infection or active intraocular inflammation in the study eye
• Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision in the study eye
• Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than DME in the study eye
• Other protocol-specified inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm B: Ranibizumab; Participants will receive ranibizumab, 0.5 mg IVT, from Day 1 and Q4W in combination with sham up to Week 44, for a total of 12 injections, followed by an observational period up to Week 72.	Drug: Ranibizumab; Ranibizumab will be administered by IVT injection in the study eye.; Other Names: Lucentis; Other: Sham Procedure; 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.
Experimental: Arm A: Vamikibart + Ranibizumab; Participants will receive vamikibart, 1 milligram (mg) administered as intravitreal (IVT) injection in combination with ranibizumab, 0.5 mg IVT, on Day 1 and every fourth week (Q4W) up to Week 44, for a total of 12 injections, followed by an observational period up to Week 72.	Drug: Ranibizumab; Ranibizumab will be administered by IVT injection in the study eye.; Other Names: Lucentis; Drug: Vamikibart; Vamikibart will be administered by IVT injection in the study eye.; Other Names: RO7200220

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged Over Week 44 and Week 48 in Treatment-naïve Participants	BCVA was measured via Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters using a set of three Precision vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity (VA) examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores and gain in BCVA from baseline indicate improvement in VA. This analysis used a Mixed Model for Repeated Measurements (MMRM) model.	Baseline, Week 44 and Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Systemic and Ocular Adverse Events (AEs)	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.	Up to Week 72
Change From Baseline in BCVA Averaged Over Week 44 and Week 48 in Previously Treated Participants	BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores and gain in BCVA from baseline indicate improvement in VA. This analysis used a MMRM model.	Baseline, Week 44 and Week 48
Change From Baseline in BCVA Averaged Over Week 44 and Week 48 in Overall ITT Population	BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores and gain in BCVA from baseline indicate improvement in VA. This analysis used a MMRM model.	Baseline, Week 44 and Week 48
Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Treatment-naïve Participants	BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores and gain in BCVA from baseline indicate improvement in VA. This analysis used a MMRM model.	Baseline, Week 32 and Week 36
Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Previously Treated Participants	BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores and gain in BCVA from baseline indicate improvement in VA. This analysis used a MMRM model.	Baseline, Week 32 and Week 36
Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Overall ITT Population	BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores and gain in BCVA from baseline indicate improvement in VA. This analysis used a MMRM model.	Baseline, Week 32 and Week 36
Change From Baseline in BCVA Averaged Over Week 20 and Week 24 in Treatment-naïve Participants	BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores and gain in BCVA from baseline indicate improvement in VA. This analysis used a MMRM model.	Baseline, Week 20 and Week 24
Change From Baseline in BCVA Averaged Over Week 20 and Week 24 in Previously Treated Participants	BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores and gain in BCVA from baseline indicate improvement in VA. This analysis used a MMRM model.	Baseline, Week 20 and Week 24
Change From Baseline in BCVA Averaged Over Week 20 and Week 24, in Overall ITT Population	BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores and gain in BCVA from baseline indicate improvement in VA. This analysis used a MMRM model.	Baseline, Week 20 and Week 24
Change From Baseline in BCVA Over Time in Overall ITT Population	BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores and gain in BCVA from baseline indicate improvement in VA. This analysis used a MMRM model.	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA Over Time in Overall ITT Population	BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores indicate improvement in VA. Percentages have been rounded off.	Up to Week 72
Percentage of Participants Losing ≥ 15, ≥ 10, or ≥ 5 Letters in BCVA Over Time in Overall ITT Population	BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 to 100 letters. Higher scores indicate improvement in VA. Percentages have been rounded off.	Up to Week 72
Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time	BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 (Snellen equivalent <20/800) to 100 (Snellen equivalent of 20/10) letters. Higher scores indicate improvement in VA. Percentages have been rounded off.	Baseline, Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time	BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 (Snellen equivalent <20/800) to 100 (Snellen equivalent of 20/10) letters. Higher scores indicate improvement in VA. Percentages have been rounded off.	Baseline, Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Percentage of Participants With BCVA ≤ 38 Letters (20/200 Snellen Equivalent) Over Time	BCVA was measured via ETDRS chart at a starting distance of 4 meters using a set of three Precision vision^TM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified VA examiner. The BCVA letter score ranges from 0 (Snellen equivalent <20/800) to 100 (Snellen equivalent of 20/10) letters. Higher scores indicate improvement in VA. Percentages have been rounded off.	Baseline, Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Change From Baseline in Central Subfield Thickness (CST) Averaged Over Week 44 and Week 48 in Treatment-naïve Participants	CST was defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 millimetre (mm) central subfield. CST was measured using spectral domain optical coherence tomography (SD-OCT). Negative change from baseline values denotes improvement. This analysis used a MMRM model.	Baseline, Week 44 and Week 48
Change From Baseline in CST Averaged Over Week 44 and Week 48 in Previously Treated Participants	CST was defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 mm central subfield. CST was measured using SD-OCT. Negative change from baseline values denotes improvement. This analysis used a MMRM model.	Baseline, Week 44 and Week 48
Change From Baseline in CST Averaged Over Week 44 and Week 48 in Overall ITT Population	CST was defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 mm central subfield. CST was measured using SD-OCT. Negative change from baseline values denotes improvement. This analysis used an MMRM model.	Baseline, Week 44 and Week 48
Change From Baseline in CST Averaged Over Week 32 and Week 36 in Treatment-naïve Participants	CST was defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 mm central subfield. CST was measured using SD-OCT. Negative change from baseline values denotes improvement. This analysis used an MMRM model.	Baseline, Week 32 and Week 36
Change From Baseline in CST Averaged Over Week 32 and Week 36 in Previously Treated Participants	CST was defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 mm central subfield. CST was measured using SD-OCT. Negative change from baseline values denotes improvement. This analysis used an MMRM model.	Baseline, Week 32 and Week 36
Change From Baseline Averaged Over Week 32 and Week 36 in Overall ITT Population	CST was defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 mm central subfield. CST was measured using SD-OCT. Negative change from baseline values denotes improvement. This analysis used an MMRM model.	Baseline, Week 32 and Week 36
Change From Baseline in CST Averaged Over Week 20 and Week 24 in Treatment-naïve Participants	CST was defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 mm central subfield. CST was measured using SD-OCT. Negative change from baseline values denotes improvement. This analysis used an MMRM model.	Baseline, Week 20 and Week 24
Change From Baseline in CST Averaged Over Week 20 and Week 24 in Previously Treated Participants	CST was defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 mm central subfield. CST was measured using SD-OCT. Negative change from baseline values denotes improvement. This analysis used an MMRM model.	Baseline, Week 20 and Week 24
Change From Baseline in CST Averaged Over Week 20 and Week 24 in Overall ITT Population	CST was defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 mm central subfield. CST was measured using SD-OCT. Negative change from baseline values denotes improvement. This analysis used an MMRM model.	Baseline, Week 20 and Week 24
Change From Baseline in CST Over Time in Overall ITT Population	CST was defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 mm central subfield. CST was measured using SD-OCT. Negative change from baseline values denotes improvement. This analysis used an MMRM model.	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Percentage of Participants With Absence of DME Over Time in Overall ITT Population	Absence of DME was defined as CST < 325 μm for Spectralis SD-OCT, or < 315 μm for Cirrus SD-OCT or Topcon SD-OCT. Percentages have been rounded off.	Baseline, Weeks 4, 8, 12, 16, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Percentage of Participants With Absence of Intraretinal Fluid (IRF) Over Time in Overall ITT Population	The absence of IRF in the study eye (defined as IRF absent or definite outside center subfield only) was assessed by the central reading center using SD-OCT. The percentage of participants with absence of IRF at foveal center are reported. Percentages have been rounded off.	Baseline, Weeks 4, 12, 24, 36, 48, and 72
Percentage of Participants With Absence of Subretinal Fluid (SRF) Over Time in Overall ITT Population	The absence of SRF in the study eye (defined as SRF absent or definite outside center subfield only) was assessed by the central reading center using SD-OCT. The percentage of participants with absence of SRF at the foveal center are reported. Percentages have been rounded off.	Baseline, Weeks 4, 12, 24, 36, 48, and 72

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2021
• Primary Completion (Actual): April 17, 2024
• Study Completion (Actual): October 1, 2024

Study Registration Dates

• First Submitted: December 8, 2021
• First Submitted That Met QC Criteria: December 8, 2021
• First Posted (Actual): December 9, 2021

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Edema; Macular Edema; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Ranibizumab
• Other Study ID Numbers: BP43464; 2021-004390-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No