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: Active, not recruiting
• 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
  • Capital Federal, Argentina, C1015ABO
    • Centro Oftalmológico Dr. Charles S.A.
  • Capital Federal, Argentina, C1120AAN
    • Oftalmos
  • Ciudad Autonoma Buenos Aires, Argentina, C1061AAE
    • Buenos Aires Mácula
  • Rosario, Argentina, S2000DLA
    • Grupo Laser Vision
  • San Nicolás, Argentina, C1015ABO
    • Organizacion Medica de Investigacion
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K2B 7E9
      • The Retina Centre 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; Opthalmology
  • Jerusalem, Israel, 9112001
    • Hadassah MC; Ophtalmology
  • Petach Tikva, Israel, 4941492
    • Rabin MC; Ophtalmology
  • Rehovot, Israel, 7660101
    • Kaplan Medical Center; Ophtalmology
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky MC; Ophtalmology
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Pusan National University Hospital
  • Daegu, Korea, Republic of, 42415
    • Yeungnam University Medical Center
  • Seongnam-si, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 07301
    • Kim's Eye Hospital
• Poland
  • Gda?sk, Poland, 80-402
    • Dobry Wzrok Sp Z O O
  • Gliwice, Poland, 44-100
    • Poradnia Okulistyczna i Salon Optyczny w Gliwicach- PRYZMAT
  • Katowice, Poland, 40-514
    • Uniwersyteckie Centrum Kliniczne; UCK im prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego
  • 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, 00612
    • Emanuelli Research and Development Center LLC
• Spain
  • Madrid, Spain, 28027
    • Clinica Universitaria de Navarra; Servicio de Oftalmologia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra; Servicio de Oftalmologia
• United Kingdom
  • Gloucestershire, United Kingdom, GL1 3NN
    • Gloucestershire Hospitals NHS Foundation Trust
  • Guildford, United Kingdom, GU2 7XX
    • Royal Surrey County Hospital
  • London, United Kingdom, EC1V 2PD
    • Moorfields Eye Hospital NHS Foundation Trust
  • 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
    • Fort Lauderdale, Florida, United States, 33309
      • Pinnacle Research Institute
    • Melbourne, Florida, United States, 32901
      • Florida Eye Associates
    • Saint Petersburg, Florida, United States, 33711-1141
      • Retina Vitreous Associates of Florida
  • Maryland
    • Hagerstown, Maryland, United States, 21740-5940
      • 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
    • The Woodlands, Texas, United States, 77384-4167
      • Retina Consultants of Texas
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Rocky Mountain Retina

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	Time Frame
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged Over Week 44 and Week 48, in Treatment-naïve Participants	Baseline, Week 44 and Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean Change From Baseline in BCVA Averaged Over Week 44 and Week 48, in Previously Treated Participants	Baseline, Week 44 and Week 48
Mean Change From Baseline in BCVA Averaged Over Week 44 and Week 48, in Overall Enrolled Population	Baseline, Week 44 and Week 48
Mean Change From Baseline in BCVA Averaged Over Week 20 and Week 24, in Treatment-naïve Participants	Baseline, Week 20 and Week 24
Mean Change From Baseline in BCVA Averaged Over Week 20 and Week 24, in Previously Treated Participants	Baseline, Week 20 and Week 24
Mean Change From Baseline in BCVA Averaged Over Week 20 and Week 24, in Overall Enrolled Population	Baseline, Week 20 and Week 24
Mean Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Treatment-naïve Participants	Baseline, Week 32 and Week 36
Mean Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Previously Treated Participants	Baseline, Week 32 and Week 36
Mean Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Overall Enrolled Population	Baseline, Week 32 and Week 36
Number of Participants with Systemic and Ocular Adverse Events (AEs)	Up to Week 72
Number of Participants with Abnormal Laboratory Findings, Abnormal Vital Signs Values, or Abnormal Electrocardiogram (ECG) Parameters	Up to Week 72
Number of Participants with Abnormalities in Standard Ophthalmological Assessments	Up to Week 72
Mean Change from Baseline in BCVA Over Time	From baseline to end of study (up to Week 72)
Percentage of Participants Gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA Over Time	From baseline to end of study (up to Week 72)
Percentage of Participants Avoiding a Loss of ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA Over Time	From baseline to end of study (up to Week 72)
Percentage of of Participants with BCVA ≥ 69 Letters (20/40 Snellen Equivalent) or ≥ 84 Letters (20/20 Snellen Equivalent) Over Time	From baseline to end of study (up to Week 72)
Percentage of Participants with BCVA ≤38 Letters (20/200 Snellen Equivalent) Over Time	From baseline to end of study (up to Week 72)
Change from Baseline in Central Subfield Thickness (CST) at Week 48	Baseline, Week 48
Change from Baseline in CST at Week 36	Baseline, Week 36
Change from Baseline in CST at Week 24	Baseline, Week 24
Mean Change from Baseline in CST Over Time	From baseline to end of study (up to Week 72)
Percentage of Participants with Absence of Diabetic Macular Edema Over Time	From baseline to end of study (up to Week 72)
Number of Participants with Absence of Intraretinal Fluid and/or Subretinal Fluid Over Time	From baseline to end of study (up to Week 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 (Estimated): 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 (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; 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: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org/). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm)

Drug and device information, study documents

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