Neovascular Age-related Macular Degeneration
Conditions
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.
Interventions
DRUGTAB014 Monoclonal Antibody Injection
intravitreal injection at 1.25mg once every 4 weeks
intravitreal injection at 0.5mg once every 4 weeks
Sponsors
Zhaoke (Guangzhou) Ophthalmology Pharmaceutical Ltd.
BioDlink Biopharm Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Subjects, investigators responsible for patient care, vision examiner (including BCVA assessors), research nurses, independent central reading center staff, and the sponsor are blinded. Unmasked pharmacist, unmasked nurse, unmasked treatment administration physician and unmasked research associates will take part in this study.
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the change in BCVA of the study eye from TAB014 and ranibizumab treatment groups. | At week 52 | Best-corrected visual acuity (BCVA) letter score as measured by the ETDRS chart |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the change in BCVA of the study eye | At week 12, 24 and 36 | Best-corrected visual acuity (BCVA) letter score as measured by the ETDRS chart |
| Evaluate the proportion of subjects with an increase in BCVA of >5, >10, and >15 in the study eye | At week 12, 24 and 52 | Best-corrected visual acuity (BCVA) letter score as measured by the ETDRS chart |
| Evaluate the proportion of subjects with a BCVA loss of <5, <10, < 15 letters in the study eye | At week 12, 24 and 52 | Best-corrected visual acuity (BCVA) letter score as measured by the ETDRS chart |
| Change in central subfield thickness（CST) in the study eye | At week 12, 24, 36 and 52 | CST measured by SD-OCT as assessed by independent central reading center |
| Change in Choroidal Neovascularization (CNV) area of study eye | At week 12, 24 and 52 | CNV as assessed by independent central reading center |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety Evaluation | Baseline and every month up to week 52 | Ocular and non-ocular adverse events, serious adverse events (SAEs), adverse events of special interest (AESI), etc. will be graded according to the Ophthalmic Adverse Event Grading Scale and NIA Guidelines for Adverse Events and Serious Adverse Events (September 2018 Edition). |
| Immunogenicity Evaluation | At week 12, 24 and 52 | Detection of anti-drug antibody and/or neutralizing antibodies will be examined in approximately 80 patients with monocular nAMD and no prior anti-VEGF therapy in the non-study eye for detection of immunogenicity evaluation. |
Countries
China
Outcome results
None listed