Clinical trial NCT06422507: A Study to Learn More About How Well 8 Milligram Aflibercept Works and How Safe it is in Chinese Participants With Diabetic Macular Edema
Official title: Multi-Center, Randomized, Double-Masked, Active-Controlled, Phase 3 Study of the Efficacy and Safety of 8 mg Aflibercept in Chinese Participants With Diabetic Macular Edema
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Diabetic Macular Edema
Keywords: DME
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2024-05-21
Enrollment: 333
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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.

Detailed description: 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)

Eligibility criteria: Key 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.

Key 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.

Primary outcomes:
measure: Change from baseline in Best corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at Week 48
timeFrame: Week 0 (Baseline) to Week 48
Secondary outcomes:
measure: Change from baseline in BCVA by ETDRS letter score at Week 60
timeFrame: Week 0 (Baseline) to Week 60
measure: Participants gaining ≥15 letters at Week 48 and Week 60
timeFrame: Week 48 and Week 60
measure: Participants achieving an ETDRS letter score of at least 69 (approximate 20/40 Snellen equivalent) at Week 48
timeFrame: Week 48
measure: Participants with no Intraretinal fluid (IRF) and/or no Subretinal fluid (SRF) in the center subfield at Week 48
timeFrame: Week 48
measure: Change from baseline in central subfield thickness (CST) at Week 48
timeFrame: Week 0 (Baseline) to Week 48
measure: Change from baseline in leakage on fluorescein angiography (FA) at Week 48
timeFrame: Week 0 (Baseline) to Week 48
measure: Change from baseline in National Eye Institute Visual Function Questionnaire (NEI-VFQ) total score at Week 48
timeFrame: Week 0 (Baseline) to Week 48
measure: Occurrence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) through Weeks 48 and 60
timeFrame: Week 48 to Week 60
measure: Participants developing a treatment-emergent Anti-drug antibody (ADA) response or Nabs to aflibercept through EOS at Week 60
timeFrame: Week 60
measure: Systemic exposure to aflibercept as assessed by plasma concentrations of free, adjusted bound, and total aflibercept from baseline through Week 48
timeFrame: Week 0 (Baseline) to Week 48
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second Hospital of Anhui medical university
state: Anhui
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
state: Gansu
city: Guangzhou,
country: China
facility: Guangdong Provincial Hospital of TCM
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou First People Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Nanning
country: China
facility: The People's Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Harbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Luoyang
country: China
facility: Luoyang Third People's Hospital
state: Henan
city: Wuhan
country: China
facility: Renmin Hosp., Wuhan Univ.
state: Hubei
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
city: Nantong
country: China
facility: Affiliated hospital of Nantong university
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of NanChang University
state: Jiangxi
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun City
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: The Second Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Aier Eye Hospital (LIAONING)
state: Liaoning
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Chengdu
country: China
facility: Sichuan University West China Hospital
state: Sichuan
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: Zhejiang
country: China
facility: ZheJiang Provincial People's Hospital
state: Zhejiang
city: Erqi
country: China
facility: Zhengzhou Second People's Hospital
state: Zhengzhou
city: Beijing
country: China
facility: Beijing Aier Intech Eye Hospital
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
city: Beijing
country: China
facility: Capital Medical University (CMU) - Beijing Tongren Hospital
city: Changsha
country: China
facility: Central South University - The Second Xiangya Hospital
city: Chengdu
country: China
facility: Chengdu Aier Ophthalmology Hospital
city: Chengdu
country: China
facility: Chengdu University of Traditional Chinese Medicine - Teaching Hospital (Sichuan Province Traditional Chinese Medicine Hospital)
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical Universit
city: Guangzhou
country: China
facility: Guangzhou Aier Ophthalmology Hospital
city: Hangzhou
country: China
facility: Zhejiang University School of Medicine - The Second Affiliated Hospital
city: Hebei
country: China
facility: Hebei eye hospital
city: Henan
country: China
facility: Henan Provincial Eye Hospital
city: Jinan
country: China
facility: Jinan Second People's Hospital
city: Jinan
country: China
facility: Eye hospital of Shandong First Medical University
city: Ningxia
country: China
facility: People's Hospital of Ningxia Hui Autonomous Region - Opthalmology
city: Shandong
country: China
facility: Shandong University of Traditional Chinese Medicine Affiliated Ophthalmology Hospital
city: Shandong
country: China
facility: Weifang Ophthalmology Hospital
city: Shanghai
country: China
facility: Shanghai eye disease prevention and control center
city: Shanghai
country: China
facility: Shanghai General Hospital
city: Shanghai
country: China
facility: Shanghai Jiao Tong University School of Medicine (SJTUSM) - XinHua Hospital
city: Shanghai
country: China
facility: Eye & Ent Hospital of Fudan University
city: Shantou
country: China
facility: Joint Shantou International Eye Center (JSIEC)Shantou University & the Chinese University of Hong Kong
city: Shanxi
country: China
facility: Shanxi Eye Hospital
city: Shenyang
country: China
facility: Shenyang He Eye Specialist Hospital
city: Shenyang
country: China
facility: The Fourth People's Hospital of Shenyang
city: Shijiazhuang
country: China
facility: Shijiazhuang People's Hospital
city: Tianjin
country: China
facility: Tianjin Medical University Eye Hospital
city: Wenzhou
country: China
facility: Eye Hospital of Wenzhou Medical University
city: Xi'an
country: China
facility: Xi'an People's Hospital (Xi'an Fourth Hospital)
city: Xianyang
country: China
facility: Xianyang First People's Hospital
city: Hong Kong
country: Hong Kong
facility: Grantham Hospital
city: Tseung Kwan O
country: Hong Kong
facility: Tseung Kwan O Hospital
Study officials:
References: