NCT06422507

Brief Summary

Researchers are looking for a better way to treat people who have diabetic macular edema. Diabetic macular edema (DME) is a diabetes-related eye disorder. In DME, the macula, which is the central part of the retina at the back of the eye, swells up resulting in vision problems. This happens due to leakage of fluid from damaged blood vessels. The study treatment, 8 milligram (mg) aflibercept is injected into the eye. It works by blocking a protein called vascular endothelial growth factor (VEGF) which causes abnormal growth and leakage of blood vessels at the back of the eye. A lower dose of aflibercept (2 mg) is already approved for the treatment of DME. Based on the findings of another study, the higher dose of aflibercept (8 mg) is expected to reduce the frequency of injections required for treating DME while being equally safe and working as well as the lower dose. The higher dose could make it easier to treat DME and improve quality of life for people with DME. The main purpose of this study is to learn if high-dose (8 mg) aflibercept given every 16 weeks works as well as low-dose (2 mg) aflibercept given every 8 weeks in Chinese participants. For this, the researchers will compare the change in participants' 'best corrected visual acuity' (BCVA) after 48 weeks of starting the treatment. BCVA is the clearest vision a participant can have with the help of corrective lenses, such as glasses. It will be measured by the number of letters the participant can read on an eye chart. This is known as their Early Treatment Diabetic Retinopathy Study (ETDRS) letter score. Participants will be randomly (by chance) assigned to one of two treatment groups to receive study treatment as an injection into the eye up to Week 56:

  • 2 mg aflibercept every 8 weeks after receiving 5 initial monthly doses
  • 8 mg aflibercept every 16 weeks after receiving 3 initial monthly doses Each participant will be in the study for around 63 weeks with up to 18 visits to the study site. This includes:
  • one visit up to 21 days before the treatment starts during which the doctors will confirm that the participant can take part in the study
  • 16 visits during which the treatment will be given. Most of these visits will have a gap of 4 weeks except for one visit that will happen a few days after the previous visit
  • one visit 4 weeks after the treatment ends During the study, the doctors and their study team will:
  • check the participants' vision and their overall eye health using different eye tests
  • check participants' health by performing tests such as blood and urine tests
  • ask the participants questions about the disease and study treatment and how these impact their quality of life
  • ask the participants what adverse events they are having An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective of whether they think they are related to the study treatment. Access to study treatment after the end of this study is not planned. Participants can switch to available approved treatments for DME.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
333

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started May 2024

Geographic Reach
2 countries

52 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 15, 2024

Completed
6 days until next milestone

First Posted

Study publicly available on registry

May 21, 2024

Completed
8 days until next milestone

Study Start

First participant enrolled

May 29, 2024

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 29, 2025

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 25, 2026

Completed
Last Updated

March 31, 2026

Status Verified

March 1, 2026

Enrollment Period

1.6 years

First QC Date

May 15, 2024

Last Update Submit

March 30, 2026

Conditions

Keywords

DME

Outcome Measures

Primary Outcomes (1)

  • Change from baseline in Best corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at Week 48

    The primary endpoint is the change from baseline in BCVA at Week 48. Efficacy analyses will be conducted using the Full analysis set (FAS). The primary efficacy analysis will be a comparison between 2 comparative arms: HDq16 vs. 2q8. The primary efficacy variable (Change from baseline in BCVA by ETDRS letter score at Week 48) will be analyzed using FAS with an Mixed Model for Repeated Measurements (MMRM) analysis model. The model includes baseline BCVA as a covariate, treatment group, baseline CST category, baseline BCVA category, prior DME treatment, and visit as fixed effects, and interaction terms for treatment by visit and baseline BCVA by visit. A Kenward-Roger approximation will be used for the denominator degrees of freedom.

    Week 0 (Baseline) to Week 48

Secondary Outcomes (10)

  • Change from baseline in BCVA by ETDRS letter score at Week 60

    Week 0 (Baseline) to Week 60

  • Participants gaining ≥15 letters at Week 48 and Week 60

    Week 48 and Week 60

  • Participants achieving an ETDRS letter score of at least 69 (approximate 20/40 Snellen equivalent) at Week 48

    Week 48

  • Participants with no Intraretinal fluid (IRF) and/or no Subretinal fluid (SRF) in the center subfield at Week 48

    Week 48

  • Change from baseline in central subfield thickness (CST) at Week 48

    Week 0 (Baseline) to Week 48

  • +5 more secondary outcomes

Study Arms (2)

2 mg aflibercept

ACTIVE COMPARATOR

Participants that will be enrolled to this treatment arm will receive 2 mg aflibercept every 8 weeks following 5 initial monthly doses starting at Baseline (visit 2) (2q8) for the chosen "study eye". Randomization will be stratified according to baseline Central subfield thickness (CST) (\<400 µm, ≥400 µm), baseline Best corrected visual acuity (BCVA) (\<60 vs. ≥60 ETDRS letters) and prior treatment for DME.

Drug: 2 mg aflibercept (EYLEA, BAY 86-5321)Other: Sham

8 mg aflibercept (high dose)

EXPERIMENTAL

Participants that will be enrolled to this treatment arm will receive 8 mg (high dose - HD) aflibercept every 16 weeks following 3 initial monthly doses, starting at Baseline (Visit 2) (HDq16) for the chosen "study eye". Randomization will be stratified according to baseline Central subfield thickness (CST) (\<400 µm, ≥400 µm), baseline Best corrected visual acuity (BCVA) (\<60 vs. ≥60 ETDRS letters) and prior treatment for DME.

Drug: 8 mg aflibercept (BAY 86-5321) (High Dose)Other: Sham

Interventions

High-dose (HD) aflibercept is the sponsor's study intervention under investigation. Dose formulation: solution in vial. Unit dose strength: 114.3 mg/mL, Dosage Level: 8 mg (70 µL), Route of Administration: Intravitreal (IVT) injection every 16 weeks following 3 initial monthly doses. Packaging/ Labeling: Study Intervention will be provided in sterile 3 mL glass vials. Each vial will be labeled as required per country requirement.

8 mg aflibercept (high dose)

Aflibercept 2 mg is the sponsor's active comparator. Dose formulation: solution in vial. Unit dose strength: 40 mg/mL, Dosage Level: 2 mg (50 µL), Route of Administration: Intravitreal (IVT) injection every 8 weeks following 5 initial monthly doses. Packaging/ Labeling: Study Intervention will be provided in sterile 2 mL glass vials. Each vial will be labeled as required per country requirement. Aflibercept 2 mg for the non-study "fellow eye" treatment is considered an auxiliary medicinal product (AxMP) in this study. Fellow eye treatment will be allowed with 2 mg aflibercept, at the investigator's discretion for indications approved by governing authorities. The treated fellow eye will not be considered an additional study eye.

2 mg aflibercept
ShamOTHER

To preserve masking, sham injections will be performed for all participants at treatment visits in which participants do not receive an active injection through Week 56. Sham kits will be assigned for visits requiring sham injections. The sham kits are empty but should be handled in the same way as the active study intervention kits. Sham injections will be given on visits when an active injection is not planned. During the study treatment period all participants will receive either an active injection (8 mg or 2 mg aflibercept) or a sham injection (for masking purposes) following their assigned treatment group and eligibility for Dose regimen modification (DRM).

2 mg aflibercept8 mg aflibercept (high dose)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Men or women ≥18 years of age
  • Chinese participants with type 1 or type 2 diabetes mellitus and diabetic macular edema (DME) with central involvement defined as CST ≥300 µm (or ≥320 µm on Heidelberg Spectralis) in the study eye as determined by the reading center at the screening visit and confirmed by the site at baseline visit
  • BCVA early treatment diabetic retinopathy study (ETDRS) letter score of 78 to 24 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye at the screening and baseline visits with decreased vision determined to be primarily the result of DME
  • Women of childbearing potential (WOCBP) or men who are sexually active with partners of childbearing potential must agree to use highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 4 months after the last administration of study intervention.

You may not qualify if:

  • Evidence of macular edema due to any cause other than diabetes mellitus in either eye
  • Active proliferative diabetic retinopathy in the study eye
  • Panretinal laser photocoagulation (PRP) or macular laser photocoagulation in the study eye within 12 weeks (84 days) of the screening visit
  • IVT anti-VEGF treatment (aflibercept, ranibizumab, bevacizumab, conbercept, faricimab, brolucizumab, pegaptanib sodium) in the study eye within 12 weeks (84 days) of the screening visit
  • Previous use of topical steroids within 4 weeks (28 days) of the screening visit or of intraocular or periocular corticosteroids in the study eye within 16 weeks (112 days) of the screening visit, or ILUVIEN or OZURDEX IVT implants at any time
  • Prior ocular investigational agents (that have not been approved) in either eye (e.g., IVT, suprachoroidal injections, ocular implants, etc.) at any time.
  • Previous treatment with an investigational or approved intraocular gene therapy or cell therapy in either eye at any time.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (52)

The Second Hospital of Anhui medical university

Hefei, Anhui, 230601, China

Location

Beijing Hospital

Beijing, Beijing Municipality, 100730, China

Location

Lanzhou University Second Hospital

Lanzhou, Gansu, 730030, China

Location

Guangdong Provincial Hospital of TCM

Guangzhou, Guangdong, 510120, China

Location

Guangzhou First People Hospital

Guangzhou, Guangdong, 510180, China

Location

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, 510280, China

Location

The People's Hospital of Guangxi Zhuang Autonomous Region

Nanning, Guangxi, 530021, China

Location

The First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, 150001, China

Location

Luoyang Third People's Hospital

Luoyang, Henan, 471002, China

Location

Renmin Hosp., Wuhan Univ.

Wuhan, Hubei, 430040, China

Location

Nanjing First Hospital

Nanjing, Jiangsu, 210006, China

Location

Affiliated hospital of Nantong university

Nantong, Jiangsu, 226006, China

Location

The First Affiliated Hospital of NanChang University

Nanchang, Jiangxi, 330006, China

Location

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330200, China

Location

The Second Hospital of Jilin University

Changchun, Jilin, 130000, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130061, China

Location

Aier Eye Hospital (LIAONING)

Shenyang, Liaoning, China

Location

Shanxi Bethune Hospital

Taiyuan, Shanxi, 030032, China

Location

Sichuan University West China Hospital

Chengdu, Sichuan, MISSING, China

Location

Taizhou Hospital of Zhejiang Province

Taizhou, Zhejiang, 317099, China

Location

Zhengzhou Second People's Hospital

Erqi, Zhengzhou, 450015, China

Location

Beijing Aier Intech Eye Hospital

Beijing, 100000, China

Location

Beijing Friendship Hospital, Capital Medical University

Beijing, 100050, China

Location

Capital Medical University (CMU) - Beijing Tongren Hospital

Beijing, 100062, China

Location

Central South University - The Second Xiangya Hospital

Changsha, 410007, China

Location

Chengdu Aier Ophthalmology Hospital

Chengdu, 610041, China

Location

Chengdu University of Traditional Chinese Medicine - Teaching Hospital (Sichuan Province Traditional Chinese Medicine Hospital)

Chengdu, 610072, China

Location

The First Affiliated Hospital of Chongqing Medical Universit

Chongqing, 400042, China

Location

Guangzhou Aier Ophthalmology Hospital

Guangzhou, 510288, China

Location

Zhejiang University School of Medicine - The Second Affiliated Hospital

Hangzhou, 310003, China

Location

Hebei eye hospital

Hebei, 050010, China

Location

Henan Provincial Eye Hospital

Henan, 450008, China

Location

Jinan Second People's Hospital

Jinan, 250021, China

Location

Eye hospital of Shandong First Medical University

Jinan, 250299, China

Location

People's Hospital of Ningxia Hui Autonomous Region - Opthalmology

Ningxia, 750002, China

Location

Shandong University of Traditional Chinese Medicine Affiliated Ophthalmology Hospital

Shandong, 250299, China

Location

Weifang Ophthalmology Hospital

Shandong, 261041, China

Location

Shanghai eye disease prevention and control center

Shanghai, 200041, China

Location

Shanghai General Hospital

Shanghai, 200080, China

Location

Shanghai Jiao Tong University School of Medicine (SJTUSM) - XinHua Hospital

Shanghai, 200092, China

Location

Eye & Ent Hospital of Fudan University

Shanghai, 200126, China

Location

Joint Shantou International Eye Center (JSIEC)Shantou University & the Chinese University of Hong Kong

Shantou, 515041, China

Location

Shanxi Eye Hospital

Shanxi, 030002, China

Location

Shenyang He Eye Specialist Hospital

Shenyang, 110034, China

Location

The Fourth People's Hospital of Shenyang

Shenyang, 110082, China

Location

Shijiazhuang People's Hospital

Shijiazhuang, 050011, China

Location

Tianjin Medical University Eye Hospital

Tianjin, 300384, China

Location

Eye Hospital of Wenzhou Medical University

Wenzhou, 325027, China

Location

Xi'an People's Hospital (Xi'an Fourth Hospital)

Xi'an, 710005, China

Location

Xianyang First People's Hospital

Xianyang, 712099, China

Location

Grantham Hospital

Hong Kong, Hong Kong SAR, 00000, Hong Kong

Location

Tseung Kwan O Hospital

Tseung Kwan O, New Territories, 00000, Hong Kong

Location

MeSH Terms

Interventions

afliberceptsalicylhydroxamic acid

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Masking Details
The study will be conducted in double-masked fashion. Study participants and masked study site personnel will remain masked to all randomization assignments throughout the study. The Sponsor personnel who are in regular contact with the study site will remain masked to all participant randomization assignments. The operational conduct of the study after the primary analysis at Week 48 will be maintained by a masked team. No decisions on data will be taken by any of the unmasked study personnel. To preserve masking, sham injections will be performed for all participants at treatment visits in which participants do not receive an active injection through Week 56.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: The study duration for a participant is approx 63 weeks. EOS is defined as the last visit of the last participant. HD aflibercept is the sponsor's study intervention under investigation. 322 participants will be randomized into 2 treatment groups in a ratio of 1:1 to receive either 2 mg aflibercept every 8 weeks following 5 initial monthly doses (2q8) or HD aflibercept (8mg) every 16 weeks following 3 initial monthly doses (HDq16). Randomization will be stratified according to baseline Central subfield thickness (CST \<400µm, ≥400µm), baseline BCVA (\<60 vs ≥60 ETDRS letters) and prior treatment for DME. Only 1 eye per participant is identified as the study eye. If a participant's fellow (non-study) eye has DME or Neovascular age-related macular degeneration (nAMD) that requires anti-Vascular endothelial growth factor (VEGF) treatment during the participant's involvement in the study, this eye should be treated with EYLEA (2mg aflibercept) and won't be considered an additional study eye.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 15, 2024

First Posted

May 21, 2024

Study Start

May 29, 2024

Primary Completion

December 29, 2025

Study Completion

March 25, 2026

Last Updated

March 31, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will not share

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Locations