Clinical trial NCT05461339: TAB014 Compared to Lucentis® in Patients with Neovascular Age-related Macular Degeneration
Official title: A Phase III, Randomized, Multicenter, Doubled-blind Clinical Trial Comparing the Efficacy and Safety of TAB014 and Lucentis in Neovascular Age-related Macular Degeneration (nAMD) Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Neovascular Age-related Macular Degeneration
Lead sponsor: TOT Biopharm Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Zhaoke (Guangzhou) Ophthalmology Pharmaceutical Ltd.
First posted: 2022-07-18
Enrollment: 488
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a randomized, multi-center, double blind, Lucentis controlled non-inferiority study in neovascular age-related macular degeneration patients. The objective of this study is to compare the efficacy and safety of TAB014 and ranibizumab (Lucentis).

Detailed description: Primary Objectives:

To evaluate the efficacy of TAB014 compared to Lucentis in neovascular age-related macular degeneration patients

Secondary Objectives:

1. To evaluate the safety of TAB014 compared to Lucentis in neovascular age-related macular degeneration patients.
2. To evaluate the immunogenicity of TAB014 in neovascular age-related macular degeneration patients.

Eligibility criteria: Inclusion Criteria:

1. Patients must be \> 50 years old, male or female;
2. Confirmed active subfoveal or juxtafoveal choroidal neovascularization (CNV) secondary to nAMD in the study eye;
3. BCVA letter score between 15 and 73 (inclusive) by the ETDRS chart during the screening period ;
4. Confirmed by independent central reading center:

   1. Total lesion area ≤ 12 optic disc areas in the study eye,
   2. Fibrotic, scarring or atrophy \< 50% of total lesion area, without involving the fovea,
   3. Retinal hemorrhage involving the foveal or intraretinal hemorrhage \< 4 optic disc area,
5. Able to understand and personally sign informed consent form.

Exclusion Criteria:

1. Ophthalmic Treatment history:

   1. Intravitreal injection of an anti-VEGF drug (ranibizumab, bevacizumab, aflibercept or conbercept, etc.) in any eye within 90 days prior to randomization;
   2. Prior vitrectomy, panretinal photocoagulation, laser treatment of the foveal area or ocular treatment/surgery for nAMD in the study eye; or history of corneal transplantation or corneal dystrophy, treatment with verteporfin, external radiation therapy of the head or the eye, transpupillary hyperthermia;
   3. Prior intra-ocular (including cataract) surgery in the study eye within 90 days before randomization, or surgery to the exterior eye within 28 days before randomization;
   4. Intravitreal therapy in the study eye (e.g. steroids or device implants) within 180 days before randomization;
   5. PDT (Photodynamic Therapy) in the non-study eye within 30 days before screening;
   6. Central serous chorioretinopathy (CSC) in the study eye;
2. The non-study eye confirmed to have a BCVA on ETDRS chart of \< 18 letters during screening;
3. Myopia more than -8.0 diopters of refractive error in study eye; For patients who have undergone refractive surgery or cataract surgery, refraction must not have been greater than -8.0 diopters prior to surgery;
4. Absence of the crystalline lens (unless there has been artificial lens replacement), or presence of posterior lens capsule rupture, or YAG laser posterior capsulotomy received 30 days before randomization or expect to receive during the study period in study eye;
5. Ocular disorders in the study eye as determined by the investigator at the present time: (a) effects on the central vision, or (b) increasing safety risk for the subject, or (c) affecting efficacy, safety evaluation or sampling, or (d) having ocular diseases requiring surgical or medical intervention
6. In the study eye, (a) presence of uncontrolled glaucoma at randomization, or (b) prior glaucoma surgery, or (c) advanced glaucoma or optic neuropathy, affecting or endangering the central visual field;
7. Active intraocular, extraocular, or periocular inflammation or infection in either eye at randomization;
8. History of idiopathic or autoimmune-associated uveitis in either;
9. Active Hepatitis B, C or syphillis; HIV antibody positive; presence of any immune deficient, and/or immune suppressed illnesses;
10. Poorly controlled hypertension after receiving the best possible therapy;
11. Diabetic patients with HbA1c \>10%;
12. Any unmanageable clinical illness; Severe liver and kidney abnormalities；dysfunction of blood coagulation; cardiovascular events within 180 days before randomization and determined by investigator can affect subject safety evaluation or increase subject risk;
13. Prior significant allergic reactions to biological products, or known allergic reactions to bevacizumab, ranibizumab, or study related medication (including fluorescein or indocyanin green), pupillary dilating agents, anaesthetic agents, or anti-infective agents;
14. Anti-VEGF therapy within 90 days prior to randomization; subjects are allowed to take any dietary supplements, vitamins or minerals;
15. Continuous systemic use ≥ 30days of corticosteroids within 90 days before randomization, or systemic use of corticosteroids within 5 days before randomization;
16. Necessity to continue use of prohibited agents (drugs known to be toxic to the lens, retina, or optic nerve, including deoxyamine, chloroquine/hydroxychloroquine (braquinib), tamoxifen, phenothiazines, and ethambutol);
17. Participation in a study trial involving any drug or device therapy (other than vitamins and minerals) within 90 days prior to randomization; And the use of any other experimental drugs or experimental interventions other than those of this study (e.g. isostoluent blood thinning, intravitreal tissue plasminogen activators) is prohibited during the study period;
18. Pregnant or lactating women, or those with plans for pregnancy during or within 6 months of study termination (including male subjects). Premenopausal woman testing positive for pregnancy during screening or is reluctant to use reliable contraceptive methods during the study periods;
19. Other conditions that are considered not acceptable to be enrolled in the study by the investigator.

Primary outcomes:
measure: Evaluate the change in BCVA of the study eye from TAB014 and ranibizumab treatment groups.
timeFrame: At week 52
Secondary outcomes:
measure: Evaluate the change in BCVA of the study eye
timeFrame: At week 12, 24 and 36
measure: Evaluate the proportion of subjects with an increase in BCVA of >5, >10, and >15 in the study eye
timeFrame: At week 12, 24 and 52
measure: Evaluate the proportion of subjects with a BCVA loss of <5, <10, < 15 letters in the study eye
timeFrame: At week 12, 24 and 52
measure: Change in central subfield thickness（CST) in the study eye
timeFrame: At week 12, 24, 36 and 52
measure: Change in Choroidal Neovascularization (CNV) area of study eye
timeFrame: At week 12, 24 and 52
Other outcomes:
measure: Safety Evaluation
timeFrame: Baseline and every month up to week 52
measure: Immunogenicity Evaluation
timeFrame: At week 12, 24 and 52
Locations:
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Aier Intech Eye Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People'S Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Tongren Hospital, Cmu
state: Beijing
city: Jilin
country: China
facility: The First Hospital of Jilin University
state: Changchun
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical
state: Guangdong
city: Guangzhou
country: China
facility: Zhongshan Ophthalmic Center, Sun Yat-Sen University
state: Guangdong
city: Shantou
country: China
facility: Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Aier Eye Hospital
state: Guangdong
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
state: Guizhou
city: Cangzhou
country: China
facility: Cangzhou Central Hospital
state: Hebei
city: Xingtai
country: China
facility: Hebei Eye Hospital
state: Hebei
city: Ha'erbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Kaifeng
country: China
facility: Kaifeng Central Hopital
state: Henan
city: Zhengzhou
country: China
facility: Henan Eye Hospital& Henan Eye Institute
state: Henan
city: Zhengzhou
country: China
facility: Zhengzhou Second Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Shiyan
country: China
facility: Taihe Hospital (Affiliated Hospital of Hubei University of Medicine)
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital® Tongji Medical Collehe of Hust
state: Hubei
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Central theater General Hospital
state: Hubei
city: Wuhan
country: China
facility: Wuhan Puren Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Aier Eye Hospital(Changsha)
state: Hunan
city: Wuxi
country: China
facility: Wuxi No.2 People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Affiliated Eye Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Dalian
country: China
facility: Dalian No.3 People'S Hospital
state: Liaoning
city: Shenyang
country: China
facility: The Fourth People's Hospital of Shenyang
state: Liaoning
city: Shenyang
country: China
facility: Shenyang He Eye Hospital
state: Liaoning
city: Weifang
country: China
facility: Weifang Eye Hospital Co., Ltd.
state: Shandong
city: Shanghai
country: China
facility: Shanghai Eye Disease Prevention and Treatment Center
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tenth People's Hospital(Tenth People's Hospital of Tongji Unversity)
state: Shanghai
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
city: Changzhi
country: China
facility: Changzhi People'S Hospital
state: Shanxi
city: Jinzhong
country: China
facility: The First People's Hospital of Jinzhong(Jinzhong Hospital Affiliated to Shanxi Medical University)
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Eye Hospital
state: Shanxi
city: Xi'an
country: China
facility: Xi'an No.1 Hospital
state: Shanxi
city: Xi'an
country: China
facility: Xi'An Fourth Hospital
state: Shanxi
city: Chengdu
country: China
facility: Chengdu Aier Eye Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Chengdu
country: China
facility: Ineye Hospital of Chengdu University of TCM
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Eye Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University Eye Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine (FAHZU)
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People'S Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: Eye Hospital, WMU
state: Zhejiang
city: Beijing
country: China
facility: Peking Union Medical College Hospital
Study officials:
affiliation: Peking Union Medical College Hospital
name: Youxin Chen, PhD
role: PRINCIPAL_INVESTIGATOR
References: