Vamikibart in Participants With Uveitic Macular Edema

Study Overview
=================
Brief Summary
-----------------
This study will assess the efficacy and safety of vamikibart in participants with uveitic macular edema.

Official Title
-----------------
A Phase III, Multicenter, Randomized, Double-Masked, Sham-Controlled Study to Investigate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Vamikibart Administered Intravitreally in Patients With Uveitic Macular Edema

Conditions
-----------------
Uveitic Macular Edema

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female participants: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception as defined by the protocol Diagnosis of macular edema associated with non-infectious uveitis (NIU) Diagnosis of active or inactive, acute, or chronic NIU of any etiology and of any anatomical type (anterior, intermediate, posterior, panuveitis) BCVA letter score of 73 to 19 letters (inclusive) on Early Treatment Diabetic Retinopathy Study (EDTRS)-like charts Exclusion Criteria: Evidence of active or latent syphilis infection Evidence of active or latent tuberculosis infection and/or positive tuberculosis assay, or previous or current HIV diagnosis Serious acute or chronic medical or psychiatric illness History of major ocular and non-ocular surgical procedures Uncontrolled IOP or glaucoma or chronic hypotony Any anatomical changes or media opacity in the study eye preventing evaluation of retina, vitreous, and capture of study images Prior use of IVT biologics including anti-VEGFs less than 2-4 months prior to Day 1; received IVT Methotrexate within 4 months prior to Day 1 Prior macular laser therapy, cataract surgery within 6 months and laser capsulotomy within 3 months of Day 1 Topical corticosteroids and/or topical NSAID > 3 drops per day in the 14 days prior to Day 1 (D1); intraocular or periocular corticosteroid injections in the 2 months prior to D1; subconjunctival corticosteroid injection within 1 month prior to Day 1; an OZURDEX implant in the 4 months prior to D1; YUTIQ, RETISERT or ILUVIEN implant in the 3 years prior to D1 Diagnosis of macular edema due to any cause other than NIU Any major ocular conditions that may require medical or surgical intervention during the study period to prevent vision loss

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Participants will receive 4 low-dose vamikibart intravitreal (IVT) injections every 4 weeks (Q4W) to Week 12, followed by as-needed (PRN) dosing from Week 20 to Week 48. | Drug: Vamikibart<br>* Participants will receive vamikibart IVT injection<br>* Other names: RO7200220;|
| Experimental: Arm B<br>Participants will receive 4 high-dose vamikibart IVT injections Q4W to Week 12, followed by PRN dosing from Week 20 to Week 48. | Drug: Vamikibart<br>* Participants will receive vamikibart IVT injection<br>* Other names: RO7200220;|
| Sham Comparator: Arm C<br>Participants will receive 4 sham injections Q4W to Week 12, followed by PRN sham dosing from Week 20 to Week 48. | Other: Sham<br>* Participants will receive a sham procedure that mimics an IVT injection.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with ≥ 15 letter improvement from baseline in best-corrected visual acuity (BCVA) at Week 16 |  | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with ≥ 15 letter improvement from baseline in BCVA at Week 20 |  | Week 20 | 
| Change from baseline in BCVA at Week 16 |  | Week 16 | 
| Change from baseline in central subfield thickness (CST) at Week 16 |  | Week 16 | 
| Change from Baseline in BCVA at Weeks 20 and 52 |  | Weeks 20 and 52 | 
| Change from baseline in CST at Weeks 20 and 52 |  | Weeks 20 and 52 | 
| Proportion of participants with uveitic macular edema secondary to non-infectious uveitis (UME) resolution defined by standardized (by machine) CST threshold <325um on optical coherence tomography (OCT) from baseline at Weeks 16 and 52 |  | Weeks 16 and 52 | 
| Time to rescue treatment |  | Up to Week 52 | 
| Number of rescue treatments received |  | Up to Week 52 | 
| Type of rescue treatments received |  | Up to Week 52 | 
| Proportion of participants with ≥15 letter improvement from baseline in BCVA at Week 16 and 52 |  | Weeks 16 and 52 | 
| Proportion of participants without ≥15 letter loss from baseline in BCVA at Week 16 and 52 |  | Weeks 16 and 52 | 
| Time to first PRN injection |  | Up to Week 52 | 
| Change from baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) at Weeks 16 and 52 |  | Weeks 16 and 52 | 
| Percentage of participants with ocular adverse events (AEs) |  | Up to Week 52 | 
| Percent change from baseline in corneal endothelial cell density at Week 24 |  | Week 24 | 
| Percentage of participants with non-ocular AEs |  | Up to Week 52 | 
| Percentage of participants with adverse events of special interest (AESIs) |  | Up to Week 52 | 
| Percent change from baseline in corneal endothelial cell density at Week 52 |  | Week 52 | 
| Aqueous humor (AH) concentration of vamikibart |  | Up to Week 52 | 
| Serum concentration of vamikibart |  | Up to Week 52 | 
| Anti-drug antibody titer to vamikibart |  | Baseline to Week 52 |