{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:02:48Z","timestamp":1791806568128,"version":"4.3.4"},"reference-count":26,"publisher":"BMJ","issue":"7","funder":[{"name":"Key R&D Program of Shandong Province","award":["2022CXGC020502"],"award-info":[{"award-number":["2022CXGC020502"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Br J Ophthalmol"],"accepted":{"date-parts":[[2025,3,2]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To compare different doses and dosing regimens of RC28-E, a novel bispecific antibody that simultaneously binds vascular endothelial growth factor-A (VEGF-A) and fibroblast growth factor-2 (FGF-2), with conbercept in patients with diabetic macular edema (DME).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Prospective, randomised, active comparator-controlled, open-label, multicentre, phase 2 clinical trial.cente<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>The trial enrolled patients aged 18 years or older with centre-involving DME, best-corrected visual acuity (BCVA) of 73 to 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and central subfield thickness (CST) of 300\u2009\u00b5m or more.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients were assigned randomly to one of five treatment regimens: 1.0\u2009mg RC28-E for three initial monthly doses and then every 8 weeks (1.0mgQ8); 1.0\u2009mg RC28-E for five initial monthly doses and then on a pro re nata (PRN) basis (1.0mgPRN); 2.0\u2009mg RC28-E for three initial monthly doses and then every 8 weeks (2.0mgQ8); 2.0\u2009mg RC28-E for five initial monthly doses and then on a PRN basis (2.0mgPRN); or 0.5\u2009mg conbercept for three initial monthly doses and then on a PRN basis. Assessments were made at baseline and every 4 weeks thereafter.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measures<\/jats:title>\n                    <jats:p>The primary endpoint was the change in BCVA compared with baseline at 24 and 52 weeks. Secondary endpoints included the change in CST from baseline at 52 weeks; the proportion of patients who gained\/lost \u226515 letters, \u226510 letters and &gt;0 letter in BCVA; and the number of injections and safety outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The trial enrolled 156 patients. Mean improvements in BCVA in the RC28-E groups at week 24 were 7.1, 11.0, 7.4 and 10.5 letters for 1.0mgQ8, 1.0mgPRN, 2.0mgQ8 and 2.0mgPRN regimens, respectively, versus 9.7 letters for the conbercept group (p=0.146). By week 52, the RC28-E groups exhibited respective mean BCVA enhancements of 5.5, 9.5, 9.2 and 9.7 letters, compared with 8.4 letters of the conbercept group (p=0.469). Mean reductions in CST in the RC28-E groups at week 52 were \u2212163.2\u2009\u00b5m, \u2212136.9\u2009\u00b5m, \u2212142.5\u2009\u00b5m and \u2212153.6\u2009\u00b5m, versus \u2212160.7\u2009\u00b5m for the conbercept group (p=0.948). The Per Protocol Set analysis indicated that at 24 weeks, the BCVA improvement in the 2.0mgPRN group was significantly greater than that in the conbercept group (14.0 vs 9.8, p=0.019). In patients with poor baseline glycaemic control (HbA1c \u22657.5%), the 2.0mgPRN group showed greater BCVA improvement than the conbercept group (14.4 vs 4.2, p=0.039) at week 52. During the maintenance phase, the 2.0mgPRN group had fewer injections (2.8, 95%\u2009CI 1.8 to 3.7) compared with the conbercept group (4.4, 95%\u2009CI 3.5 to 5.2). RC28-E was generally well tolerated. The incidence of ocular adverse events in study eyes was comparable between RC28-E groups (22.6% in 1.0mgQ8 group, 26.7% in 1.0mgPRN group, 34.4% in 2.0mgQ8 group, 25.0% in 2.0\u2009mg PRN group) and conbercept group (32.3%). The number of ocular serious adverse events was 1 (1.0mgQ8), 0 (1.0mgPRN), 1 (2.0mgQ8), 2 (2.0mgPRN) and 0 (conbercept).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Intravitreous RC28-E improved BCVA and CST in eyes with centre-involved DME. Compared with conbercept, the 2.0mgPRN regimen of RC28-E was recommended due to its superior efficacy in improving vision particularly for patients with poor glycaemic control, fewer treatment injections during the maintenance phase and comparable safety profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04782115\">NCT04782115<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  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