{
  "abstract": "Objective To evaluate the safety, tolerability and preliminary efficacy of IBI324, a vascular endothelial growth factor-A/angiopoietin-2 bispecific antibody, in participants with diabetic macular oedema (DME).Methods and analysis This multicentre, open-label, phase 1 dose-escalation clinical trial consisted of a single ascending dose (SAD) stage and a multiple ascending dose (MAD) stage. 24 participants with fovea-involving DME were enrolled. SAD participants received a single intravitreal injection (IVT) of 0.5 mg, 2 mg or 4 mg IBI324 and were followed up until Day 42 post injection. In the MAD stage, six participants each received 3 monthly IVTs of 2 mg or 4 mg IBI324 and were followed up until determined as ‘treatment needed’ per prespecified criteria or until 24 weeks after first dose. The primary endpoints were incidence of dose-limiting toxicities (DLTs), adverse events (AEs) and changes in vital signs and laboratory test findings.Results No DLT, treatment-related AE, AE of special interest or ocular serious AE was reported. Treatment-emergent adverse events (TEAEs), all mild or moderate in severity, were observed in 4 (33.3%) SAD participants and 11 (91.7%) MAD participants. TEAEs of the study eye included intraocular pressure increased, conjunctival haemorrhage, allergic conjunctivitis, posterior capsular opacification and visual acuity decreased. Mean best-corrected visual acuity increase and mean central subfield thickness decrease from baseline in the study eye were observed in all dose groups, accompanied by intraretinal fluid/subretinal fluid improvements. 16 weeks after the last dose, 7 (58.3%) MAD 2 mg and 6 (50.0%) MAD 4 mg participants remained free of ‘treatment needed’.Conclusion IBI324 was well tolerated with evidence of functional and anatomical improvement in patients with DME.Trial registration number NCT05489718.",
  "authors": [
    {
      "affiliations": [
        "Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "National Clinical Research Center for Ophthalmic Diseases, Shanghai, China",
        "Shanghai Key Laboratory of Fundus Diseases, Shanghai, China",
        "Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China"
      ],
      "name": "Zilin Wang"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "National Clinical Research Center for Ophthalmic Diseases, Shanghai, China",
        "Shanghai Key Laboratory of Fundus Diseases, Shanghai, China",
        "Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China"
      ],
      "name": "Junran Sun"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "National Clinical Research Center for Ophthalmic Diseases, Shanghai, China",
        "Shanghai Key Laboratory of Fundus Diseases, Shanghai, China",
        "Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China"
      ],
      "name": "Kun Liu"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, The Second Hospital of Anhui Medical University, Hefei, Anhui, China"
      ],
      "name": "Liming Tao"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Jiangsu Province Hospital, Nanjing, Jiangsu, China"
      ],
      "name": "Qinghuai Liu"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, China"
      ],
      "name": "Miaoqin Wu"
    },
    {
      "affiliations": [
        "Innovent Biologics Suzhou Co Ltd, Suzhou, Jiangsu, China"
      ],
      "name": "Shujie Lu"
    },
    {
      "affiliations": [
        "Innovent Biologics Suzhou Co Ltd, Suzhou, Jiangsu, China"
      ],
      "name": "Junjie Deng"
    },
    {
      "affiliations": [
        "Innovent Biologics Suzhou Co Ltd, Suzhou, Jiangsu, China"
      ],
      "name": "Li Li"
    },
    {
      "affiliations": [
        "Innovent Biologics Suzhou Co Ltd, Suzhou, Jiangsu, China"
      ],
      "name": "Lei Qian"
    },
    {
      "affiliations": [
        "Tianjin Medical University Eye Hospital, Tianjin, China"
      ],
      "name": "Xiaorong Li"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "National Clinical Research Center for Ophthalmic Diseases, Shanghai, China",
        "Shanghai Key Laboratory of Fundus Diseases, Shanghai, China",
        "Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China"
      ],
      "name": "Xiaodong Sun"
    }
  ],
  "title": "Phase 1 dose-escalation study of IBI324, a VEGF-A/Ang-2 bispecific antibody, for the treatment of diabetic macular oedema",
  "uid": "a82ea057-8795-5f2f-adc8-1153596ba49a"
}