A Study to Learn More About How Well 8 Milligram Aflibercept Works and How Safe it is in Chinese Participants With Diabetic Macular Edema

NCT ID: NCT06422507

Last Updated: 2026-01-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

333 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-05-29

Study Completion Date

2026-03-22

Brief Summary

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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.

Detailed Description

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EYLEA (aflibercept 40 mg/mL solution for injection) at a dosage level of 2 mg administered intravitreally (IVT) is approved in over 100 countries for the treatment of DME. Despite the proven efficacy and safety of EYLEA in patients with DME, there remains an unmet need for alternative therapies that can decrease the burden of DME treatment via a reduction in the required frequency of IVT injections, while improving visual and anatomic outcomes. The overall one and two year results of PHOTON, a global phase 2/3 trial evaluating high dose (HD or 8 mg) aflibercept in participants with center-involved diabetic macular edema (DME), demonstrate the benefit of HD aflibercept for reducing the frequency of injections required for the treatment of DME while providing visual and anatomic outcomes non-inferior to and a safety profile indistinguishable from EYLEA, 2 mg aflibercept, the established standard of care for the treatment of DME. The observed reduction in the number of HD aflibercept injections required for the treatment of DME over 2 years in PHOTON is expected to translate into the benefit of reducing the burden of treatment and, thereby improving the quality of life for DME patients, their caregivers and health care providers. This study aims to investigate the efficacy and safety of HD aflibercept in Chinese participants with DME over 60 weeks with the primary objective of achieving non-inferior best corrected visual acuity (BCVA) with an extended dosing interval (every 16 weeks after 3 initial monthly injections) vs. 2 mg aflibercept (every 8 weeks after 5 initial monthly injections) similar to the results obtained in PHOTON. This study is designed to support the registration of HD aflibercept for the treatment of DME in China.

Primary Objective: The primary objective of the study is to determine if treatment with HD aflibercept at intervals of 16 weeks provides non-inferior best-corrected visual acuity (BCVA) compared to 2 mg aflibercept dosed every 8 weeks in Chinese participants

Secondary Objectives:

* To determine the effect of HD aflibercept vs. 2 mg aflibercept on anatomic and other visual measures of response;
* To evaluate the safety, immunogenicity and pharmacokinetics (PK) of HD aflibercept in Chinese participants.

Primary endpoint:

* Change from baseline in BCVA by ETDRS letter score at Week 48

Secondary endpoints:

* Change from baseline in BCVA by ETDRS letter score at Week 60
* Participants gaining ≥15 letters at Week 48 and Week 60
* Participants achieving an ETDRS letter score of at least 69 (approximate 20/40 Snellen equivalent) at Week 48
* Participants with no IRF and/or no SRF in the center subfield at Week 48
* Change from baseline in central subfield thickness (CST) at Week 48
* Change from baseline in leakage on fluorescein angiography (FA) at Week 48
* Change from baseline in National Eye Institute Visual Function Questionnaire (NEI-VFQ) total score at Week 48
* Occurrence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) through Weeks 48 and 60
* Participants developing a treatment-emergent ADA response or Nabs to aflibercept through EOS at Week 60
* Systemic exposure to aflibercept as assessed by plasma concentrations of free, adjusted bound, and total aflibercept from baseline through Week 48 This study is a phase 3, multi-center, randomized, double-masked, active-controlled study in Chinese participants with DME involving the center of the macula to investigate the efficacy and safety of HD aflibercept versus 2 mg aflibercept.

The primary objective of the study is to determine if treatment with HD aflibercept at 16 week intervals provides non-inferior BCVA compared to 2 mg aflibercept dosed every 8 weeks in Chinese participants.

322 eligible participants randomized in a 1:1 ratio to the following 2 treatment groups:

1. 2q8: 2 mg aflibercept every 8 weeks following 5 initial monthly doses (n=161) and
2. HDq16: HD aflibercept every 16 weeks following 3 initial monthly doses (n=161). The study consists of a screening period, a treatment period, and an end of study (EOS) visit at Week 60. The study duration for a participant is approximately 63 weeks. The EOS is defined as the last visit of the last participant. No study treatment will be administered at the EOS visit at Week 60.

HD aflibercept is the sponsor's study intervention under investigation. The following intervention groups are included in the study:

* 2 mg aflibercept every 8 weeks (2q8)
* 8 mg aflibercept every 16 weeks (HDq16)

Conditions

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Diabetic Macular Edema

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
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.

Study Groups

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2 mg aflibercept

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.

Group Type ACTIVE_COMPARATOR

2 mg aflibercept (EYLEA, BAY 86-5321)

Intervention Type DRUG

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.

Sham

Intervention Type OTHER

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).

8 mg aflibercept (high dose)

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.

Group Type EXPERIMENTAL

8 mg aflibercept (BAY 86-5321) (High Dose)

Intervention Type DRUG

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.

Sham

Intervention Type OTHER

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).

Interventions

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8 mg aflibercept (BAY 86-5321) (High Dose)

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.

Intervention Type DRUG

2 mg aflibercept (EYLEA, BAY 86-5321)

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.

Intervention Type DRUG

Sham

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).

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Bayer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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The Second Hospital of Anhui medical university

Hefei, Anhui, China

Site Status

Beijing Hospital

Beijing, Beijing Municipality, China

Site Status

Lanzhou University Second Hospital

Lanzhou, Gansu, China

Site Status

Guangdong Provincial Hospital of TCM

Guangzhou, Guangdong, China

Site Status

Guangzhou First People Hospital

Guangzhou, Guangdong, China

Site Status

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Site Status

The People's Hospital of Guangxi Zhuang Autonomous Region

Nanning, Guangxi, China

Site Status

The First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, China

Site Status

Luoyang Third People's Hospital

Luoyang, Henan, China

Site Status

Renmin Hosp., Wuhan Univ.

Wuhan, Hubei, China

Site Status

Nanjing First Hospital

Nanjing, Jiangsu, China

Site Status

Affiliated hospital of Nantong university

Nantong, Jiangsu, China

Site Status

The First Affiliated Hospital of NanChang University

Nanchang, Jiangxi, China

Site Status

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status

The Second Hospital of Jilin University

Changchun, Jilin, China

Site Status

The First Hospital of Jilin University

Changchun, Jilin, China

Site Status

Aier Eye Hospital (LIAONING)

Shenyang, Liaoning, China

Site Status

Shanxi Bethune Hospital

Taiyuan, Shanxi, China

Site Status

Sichuan University West China Hospital

Chengdu, Sichuan, China

Site Status

Taizhou Hospital of Zhejiang Province

Taizhou, Zhejiang, China

Site Status

Zhengzhou Second People's Hospital

Erqi, Zhengzhou, China

Site Status

Beijing Aier Intech Eye Hospital

Beijing, , China

Site Status

Beijing Friendship Hospital, Capital Medical University

Beijing, , China

Site Status

Capital Medical University (CMU) - Beijing Tongren Hospital

Beijing, , China

Site Status

Central South University - The Second Xiangya Hospital

Changsha, , China

Site Status

Chengdu Aier Ophthalmology Hospital

Chengdu, , China

Site Status

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

Chengdu, , China

Site Status

The First Affiliated Hospital of Chongqing Medical Universit

Chongqing, , China

Site Status

Guangzhou Aier Ophthalmology Hospital

Guangzhou, , China

Site Status

Zhejiang University School of Medicine - The Second Affiliated Hospital

Hangzhou, , China

Site Status

Hebei eye hospital

Hebei, , China

Site Status

Henan Provincial Eye Hospital

Henan, , China

Site Status

Jinan Second People's Hospital

Jinan, , China

Site Status

Eye hospital of Shandong First Medical University

Jinan, , China

Site Status

People's Hospital of Ningxia Hui Autonomous Region - Opthalmology

Ningxia, , China

Site Status

Shandong University of Traditional Chinese Medicine Affiliated Ophthalmology Hospital

Shandong, , China

Site Status

Weifang Ophthalmology Hospital

Shandong, , China

Site Status

Shanghai eye disease prevention and control center

Shanghai, , China

Site Status

Shanghai General Hospital

Shanghai, , China

Site Status

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

Shanghai, , China

Site Status

Eye & Ent Hospital of Fudan University

Shanghai, , China

Site Status

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

Shantou, , China

Site Status

Shanxi Eye Hospital

Shanxi, , China

Site Status

Shenyang He Eye Specialist Hospital

Shenyang, , China

Site Status

The Fourth People's Hospital of Shenyang

Shenyang, , China

Site Status

Shijiazhuang People's Hospital

Shijiazhuang, , China

Site Status

Tianjin Medical University Eye Hospital

Tianjin, , China

Site Status

Eye Hospital of Wenzhou Medical University

Wenzhou, , China

Site Status

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

Xi'an, , China

Site Status

Xianyang First People's Hospital

Xianyang, , China

Site Status

Grantham Hospital

Hong Kong, , Hong Kong

Site Status

Tseung Kwan O Hospital

Tseung Kwan O, , Hong Kong

Site Status

Countries

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China Hong Kong

Related Links

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https://clinicaltrials.bayer.com/study/21583

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Other Identifiers

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21583

Identifier Type: -

Identifier Source: org_study_id

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