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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Diabetic Macular Edema

Intervention / Treatment
-----------------
* Drug: Vamikibart
* Drug: Ranibizumab
* Other: Sham Procedure


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Vamikibart + Ranibizumab<br>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: Vamikibart<br>* Vamikibart will be administered by IVT injection in the study eye.<br>* Other names: RO7200220;Drug: Ranibizumab<br>* Ranibizumab will be administered by IVT injection in the study eye.<br>* Other names: Lucentis;|
| Active Comparator: Arm B: Ranibizumab<br>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<br>* Ranibizumab will be administered by IVT injection in the study eye.<br>* Other names: Lucentis;Other: Sham Procedure<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 | 
| 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) |