Efficacy and Safety of RC28-E Versus Aflibercept in Diabetic Macular Edema

A Phase III, Multicenter, Randomized, Double-blind, Active Controlled Trial of RC28-E Intravitreal Injection in Subjects With Diabetic Macular Edema

The purpose of this study is to evaluate efficacy and safety of RC28-E compared with Aflibercept in subjects with diabetic macular edema.

Study Overview

• Status: Recruiting
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Biological: RC-28E; Biological: Aflibercept

• Study Type: Interventional
• Enrollment (Estimated): 316
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Binghua Xiao; Phone Number: 86-010-58076833; Email: xiaosir522@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100010
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Youxin Chen, M.D.; Phone Number: 13801025972; Email: chenyouxinpumch@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented diagnosed with type I or type II diabetes mellitus.
• Hemoglobin A1c (HBA1c) of less than or equal to (≤) 10% within 2 months prior to Day 1.
• Ability and willingness to undertake all scheduled visits and assessments.

• The study eye must meet the following requirements:

  • macular thickening secondary to diabetic macular edema (DME) involving the center of the fovea.
  • decreased visual acuity attributable primarily to DME, the best corrected visual acuity (BCVA) 19 or more letters, 78 letters or less.

Exclusion Criteria:

• The study eye with high risk of proliferative diabetic retinopathy.
• The macular edema of the study eye is mainly caused by other diseases or factors other than DME.
• Treatment with panretinal photocoagulation or macular laser within 3 months prior to Day 1 to the study eye.
• Administration of IVT any other anti-VEGF drugs in the study eye within 3 months and/or in the other eye within 7 days prior to Day 1.
• Any intraocular long-acting or sustained release corticosteroid treatment (e.g., dexamethasone intravitreal implant) in the study eye within 6 months prior to Day 1.
• Active intraocular or periocular infection or active intraocular inflammation in either eye.
• The study eye with poorly controlled glaucoma.
• A history of idiopathic or autoimmune related uveitis in either eye.
• History of stroke (cerebrovascular accident) or myocardial infarction within 6 months prior to Day 1.
• Uncontrolled blood pressure, defined as a systolic value greater than (>)180 millimeters of mercury (mmHg) and/or a diastolic value >100 mmHg while a patient is at rest.
• Currently pregnant or breastfeeding, or intend to become pregnant during the study.
• Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision in the study eye.
• Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than DME in the study eye.
• Other protocol-specified inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RC-28E; RC-28E 2.0 mg will be initially intravitreal injected (IVT) 5 times at 4 week intervals from week 0 to week 16, then every 8 weeks until week 48.	Biological: RC-28E; Ophthalmic solution for intravitreal injection administered as a 2.0mg/50 μL per dose.
Active Comparator: Aflibercept; Aflibercept 2.0mg will be received IVT once every 4 weeks for 5 consecutive times from week 0 to week 16, then once every 8 weeks till week 48.	Biological: Aflibercept; Ophthalmic solution for intravitreal injection administered as a 2.0mg/50 μL per dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in BCVA at Week 52	BCVA=best-corrected visual acuity; Measurement of visual acuity with Early Treatment Diabetic Retinopathy Study (ETDRS) charts at a starting distance of 4 meters	Baseline, week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average change in BCVA from baseline over the period week 40 through week 52	For each subject, this endpoint is defined as the average of the changes from baseline to weeks 40, 44, 48 and 52	Baseline, weeks 40, 44, 48 and 52
Change from baseline in BCVA over time	BCVA will be assessed at each visit	Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Proportion of patients gaining >15, >10, >5, or >0 letters in BCVA from baseline at Week 52	Proportion of patients of gaining 4 types of letter counting in BCVA, respectively	Baseline, week 52
Proportion of patients avoiding a loss of >15, >10, >5, or >0 letters in BCVA from baseline at Week 52	Proportion of patients of reducing 4 types of letter counting in BCVA, respectively	Baseline, week 52
Change from baseline in CST at Week 52	CST=central subfield thickness	Baseline, week 52
Mean change from baseline in CST over a period of week 40 through week 52	CST=central subfield thickness	Baseline, weeks 40, 44, 48 and 52.
Change from baseline in CST over time	The change of CST will be assessed from baseline to 52 weeks by every 4 week intervals	Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Proportion of patients with absence of intraretinal fluid at Week 52	Proportion of patients whose intraretinal fluid are completely improved	Baseline, week 52
Proportion of patients with absence of subretinal fluid at Week 52	Proportion of patients whose subretinal fluid are completely improved	Baseline, week 52
Proportion of patients with absence of intraretinal fluid and subretinal fluid at Week 52	Proportion of patients whose intraretinal fluid and subretinal fluid are both completely improved	Baseline, week 52
Proportion of patients with a >2-step or>3-step DRS worsening from baseline on ETDRS DRSS at Week 52	DRSS=Diabetic Retinopathy Severity Scale	Baseline, week 52
Proportion of patients who develop new PDR or high risk PDR at Week 52	PDR=proliferative diabetic retinopathy	Baseline, week 52
Incidence and severity of ocular adverse events and non-ocular adverse events	during the study	0~52 weeks
Plasma concentration of RC28-E over time	during the study	Baseline, weeks 16, 36 and 48
Presence of ADAs during the study relative to the presence of ADAs at baseline	during the study	Baseline, weeks 12, 24, 36 and 52

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.
• Investigators: Principal Investigator: Youxin Chen, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: May 19, 2023
• First Submitted That Met QC Criteria: May 30, 2023
• First Posted (Actual): June 2, 2023

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: 28C005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No