A Dose Escalation Study of IBI324 in Subjects With Diabetic Macular Edema

Study Overview
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Brief Summary
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This study is designed as a Multi-center, open-label, dose escalation phase I trial to evaluate the safety and tolerability of a single and multiple intravitreal injections of IBI324 in subjects with DME

Official Title
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A Dose Escalation Phase I Clinical Study to Evaluate the Tolerability and Safety of IBI324 in Subjects With Diabetic Macular Edema(DME)

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Biological: IBI324
* Biological: IBI324
* Biological: IBI324
* Biological: IBI324
* Biological: IBI324


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to sign informed consent form and comply with visit and study procedures per protocol. Male or female subjects with age of 18 80 yrs. Diagnosis of diabetes mellitus(type 1 or 2), and current regular use of insulin or other injectable drugs or oral anti-hyperglycaemic agent for the treatment of diabetes. Visual impairment was caused by DME involving the macular fovea. Central macular sub-field thickness (CST) ≥320μm according to OCT. BCVA score of 24-73 letters using ETDRS charts (in 4 meters) in the study eye. Female subjects of childbearing age or male subjects with childbearing age female partner agree to take effective contraceptive measures from the screening period to 3 months after the end of treatment. Exclusion Criteria: Concomitant diseases that may cause subjects fail to respond to the treatment or confuse the interpretation of the study results. PDR in the study eye. Tractional retinal detachment, pre-retinal fibrosis, vitreomacular traction, or epiretinal membrane involving the fovea or disrupting the macular architecture in the study eye. Active rubeosis in the study eye. The equivalent spherical lens≤-8.00D in the study eye. The intraocular pressure>21 mmHg in the study eye. Active ocular or periocular inflammation/infection in either eye. Prior any treatment of following in the study eye: Intravitreal anti-VEGF treatment within 3 months prior to baseline; Intraocular glucocorticoid injection within 3 months prior to baseline; PRP, local/grid laser photocoagulation within 3 months prior to baseline; Any intraocular surgery (e.g. cataract surgery) within 90 days prior to baseline; The eyes were treated with lasik posterior capsulotomy or glaucoma filtration, radiotherapy 30 days before baseline; Currently untreated diabetes mellitus or previously untreated DM subjects who initiated oral or injectable antidiabetic medication or insulin <90 days; HbA1c of >10% within 28 days prior to baseline; Presence of any systemic disease: including but not limited to unstable angina; cerebrovascular accident or transient cerebral ischemia (within 6 months prior to selection); myocardial infarction (within 6 months prior to selection); serious arrhythmia requiring medical treatment; liver, kidney or metabolic diseases; or malignant tumor; History of severe hypersensitivity/allergy to active ingredients or any excipients of the study drug, or fluorescein and povidone iodine; Pregnant or lactating women or women preparing to become pregnant or breastfeeding during the study period; Participated in any clinical study of any other drug within three months prior to enrollment, or attempted to participate in other drug trials during the study; Other conditions unsuitable for enrollment judged by investigators

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treated with different doses of single intravitreal inmection of IBI324<br> | Biological: IBI324<br>* Dose 2 IBI324 of single IVT injection<br>Biological: IBI324<br>* Dose 1 IBI324 of single IVT injection<br>Biological: IBI324<br>* Dose 3 IBI324 of single IVT injection<br>|
| Experimental: treated with different doses of multiple intravitreal inmection of IBI324<br> | Biological: IBI324<br>* Dose 2 IBI324 of multiple IVT injection<br>Biological: IBI324<br>* Dose 3 IBI324 of multiple IVT injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety evaluation indicators | Incidence, relatedness and severity of all adverse events, treatment emergent adverse events and serious adverse events b) Changes in central subfield thickness by OCT compared with baseline | Through study completion, a maximum of 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of adverse events |  | Through study completion, a maximum of 24 weeks | 
| Changes in visual acuity as measured by BCVA compared with baseline |  | Through study completion, a maximum of 24 week | 
| Changes in the average thickness of the macula in the central 1 mm ETDRS grid (CST) compared with baseline |  | Through study completion, a maximum of 24 week | 
| Pharmacokinetic (PK) profiles, such as half-life time (t1/2)，etc | Positive rate of anti-drug antibody | Through study completion, a maximum of 24 weeks | 
| Immunogenicity evaluation indicators | Positive rate of anti-drug antibody | Through study completion, a maximum of 24 weeks |