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

Study Overview
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Brief Summary
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Study BP43445 is a phase II, multicenter, randomized, double-masked, active comparator-controlled study to investigate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of vamikibart administered intravitreally in participants with diabetic macular edema. Only one eye will be chosen as the study eye. The duration of the study will be up to 76 weeks.

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

Conditions
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Diabetic Macular Edema

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


Participation Criteria
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Eligibility Criteria
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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
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: 0.25 mg Vamikibart Q8W<br>Participants will receive vamikibart 0.25 milligrams (mg), by intravitreal (IVT) injection, on Day 1 and every 8th week (Q8W), up to Week 44, for a total of 6 injections. A sham procedure will be administered during study visits at which no study drug is administered to maintain masking between treatment arms. | Drug: Vamikibart<br>* Vamikibart will be administered by IVT injection as specified in each treatment arm.<br>* Other names: RO7200220;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. Sham procedure will be administered to participants in the Q8W arms at applicable visits to maintain masking between treatment arms.<br>|
| Experimental: Arm B: 1.0 mg Vamikibart Q8W<br>Participants will receive vamikibart 1.0 mg, by IVT injection, on Day 1 and Q8W, up to Week 44, for a total of 6 injections. A sham procedure will be administered during study visits at which no study drug is administered to maintain masking between treatment arms. | Drug: Vamikibart<br>* Vamikibart will be administered by IVT injection as specified in each treatment arm.<br>* Other names: RO7200220;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. Sham procedure will be administered to participants in the Q8W arms at applicable visits to maintain masking between treatment arms.<br>|
| Experimental: Arm C: 1.0 mg Vamikibart Q4W<br>Participants will receive vamikibart 1.0 mg, by IVT injection, on Day 1 and every 4th week (Q4W), up to Week 44 for a total of 12 injections. | Drug: Vamikibart<br>* Vamikibart will be administered by IVT injection as specified in each treatment arm.<br>* Other names: RO7200220;|
| Active Comparator: Arm D: 0.5 mg Ranibizumab Q4W<br>Participants will receive ranibizumab 0.5 mg, by IVT injection, on Day 1 and Q4W, up to Week 44 for a total of 12 injections. | Drug: Ranibizumab<br>* Ranibizumab 0.5 mg will be administered to the participants by IVT injection, as specified in the treatment arm.<br>* Other names: Lucentis;|

What is the study measuring?
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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 | 
| Change From Baseline in BCVA Over Time |  | From baseline up to end of study (up to Week 72) | 
| Percentage of Participants Gaining Greater Than or Equal to (≥) 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA From Baseline Over Time |  | From baseline up to end of study (up to Week 72) | 
| Percentage of Participants Avoiding a Loss of ≥ 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA From Baseline Over Time |  | From baseline up to end of study (up to Week 72) | 
| Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent), or ≥ 84 Letters (20/20 Snellen Equivalent) Over Time |  | From baseline up to end of study (up to Week 72) | 
| Percentage of Participants With BCVA of Less Than or Equal to (≤) 38 Letters (Snellen Equivalent 20/200) Over Time |  | From baseline up 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 | 
| Change From Baseline in CST Over Time |  | From baseline up to end of study (up to Week 72) | 
| Percentage of Participants With Absence of Diabetic Macular Edema (DME) Over Time |  | From baseline up to end of study (up to Week 72) | 
| Percentage of Participants With Absence of Intraretinal Fluid and/or Subretinal Fluid Over Time |  | From baseline up to end of study (up to Week 72) |