Interleukin 6 Inhibition With Vamikibart for Uveitic Macular Edema: The Phase 1 DOVETAIL Nonrandomized Clinical Trial.

Importance: Effective nonsteroidal therapies are needed for uveitic macular edema (UME). Objective: To assess the safety, tolerability, and effects associated with intravitreal (IVT) vamikibart in UME. Design, Setting, and Participants: This multipart, multicenter, open-label, multiple-ascending-dose nonrandomized clinical trial of vamikibart (RO7200220), a novel IVT anti-interleukin 6 monoclonal antibody, included monotherapy in participants with UME secondary to noninfectious uveitis (NIU). DOVETAIL was conducted from July 2019 to November 2023 at 18 sites in the US. Adults with UME secondary to NIU (optical coherence tomography central subfield thickness [CST] ≥325 µm) were eligible for inclusion. Data were analyzed from February 2024 to May 2024. Interventions: Participants were enrolled into 3 dose groups (0.25, 1, or 2.5 mg) and received IVT vamikibart at day 1, week 4, and week 8, followed by observation not receiving treatment until weeks 20 (2.5 mg) or 36 (0.25 or 1 mg). Main Outcomes and Measures: The primary outcomes were safety and tolerability; exploratory outcomes included best-corrected visual acuity (BCVA) and CST. Results: In this nonrandomized study, vamikibart was associated with improvements in BCVA and CST across all doses. A total of 37 participants with UME were enrolled (0.25 mg: n = 12; 1 mg: n = 12; 2.5 mg: n = 13); 22 of 37 patients (59.5%) were female, and the mean (SD) age was 63.5 (15.4) years. At week 12, mean (SD) change from baseline in BCVA letter score was +9.9 (8.9), an approximate 2-line improvement (improvements in letter scores of +11.1 [8.1], +10.3 [8.0], and +8.4 [10.8] for the 0.25-mg, 1-mg, and 2.5-mg groups, respectively), and mean (SD) CST reduction was -165.1 (147.5) µm (-125.0 [135.0] µm, -188.1 [152.4] µm, and -183.6 [159.4] µm for the 3 dose groups, respectively). Of 37 participants, 36 continued vamikibart throughout the 12 weeks. Ocular adverse events (AEs) in the study eye were reported in 19 participants (51.4%), including 1 serious AE (uveitis worsening, unrelated to study drug) and 1 treatment-related AE (VA reduced transiently). No cases of retinal vasculitis (occlusive or nonocclusive) were reported. Conclusions and Relevance: These results from the phase 1 DOVETAIL nonrandomized clinical trial provide preliminary evidence supporting safety, tolerability, and potential effects of vamikibart for UME secondary to NIU. Two phase 3 clinical trials (MEERKAT [NCT05642312] and SANDCAT [NCT05642325]) are underway to further evaluate vamikibart in UME. Trial Registration: ClinicalTrials.gov Identifier: NCT06771271.