A Single-center, Open-label, Single Ascending Dose Phase 1 Study to Evaluate the Safety, Pharmacokinetics, and Tolerability of Intravitreal TK001(Recombinant Humanized Anti-VEGF Monoclonal Antibody) in Subjects With Neovascular Age-Related Macular Degeneration
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Neovascular Age-related Macular Degeneration
- Sponsor
- Jiangsu T-Mab Biopharma Co.,Ltd
- Enrollment
- 27
- Locations
- 1
- Primary Endpoint
- Frequency of ocular and systemic AEs (adverse events) and SAEs (serious adverse events) which are related to TK001
- Last Updated
- 8 years ago
Overview
Brief Summary
The purpose of this first-in-human study is to evaluate the safety, pharmacokinetics and tolerability of single ascending doses of TK001(Recombinant humanized anti-VEGF monoclonal antibody) to determine the maximum tolerated dose (MTD) in neovascular wet age-related macular degeneration (wAMD) subjects.
Detailed Description
This is an open-label, non-comparative, non-randomized, single-center phase 1 study evaluating pharmacokinetics, safety and tolerability of single intravitreal injections of TK001 in the patients with AMD.TK001 is a full-length recombinant humanized anti-VEGF monoclonal antibody. Compared with Avastin(a similar marketed product), the findings of preclinical studies suggested that TK001 might be more effective in inhibiting pathological angiogenesis, or to achieve equivalent effect with less dosage and better safety. In this study, participants will be administrated a single dose of TK001.Every subject will only accept one dose. In addition to safety and preliminary efficacy, pharmacokinetics and immunogenicity of TK001will be evaluated as well.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients or their legal representative signed informed consent
- •Aged 45 years to 80 years, male or female
- •Inpatient/Outpatient with confirmed neovascular AMD
- •Best corrected VA for the studied eye≤20/100
- •With primary or recurrent subfoveal choroidal neovascular (CNV) lesions secondary to neovascular AMD
- •Blood pressure is stable with SBP\<140 mmHg and DBP\<90 mmHg with or without treatment
Exclusion Criteria
- •Limitation of eye diseases
- •The studied eye suffered intravitreal blood within two months prior to screening
- •The studied eye suffered structural damage of retinal which involved macular center(such as epiretinal membrane, scars, laser burns, foveal atrophy, dense pigment changes, intensive subfoveal hard exudates)
- •Apparent cataract, aphakia, pseudoexfoliation syndrome, intraocular hemorrhage resulting in decreased vision, rhegmatogenous retinal detachment, macular hole, diabetic retinopathy and diabetic macular disease which need to be treated, choroidal neovascularization (CNV) for any reason except for AMD (such as ocular histoplasmosis, pathologic myopia)
- •Afferent pupillary defect(APD)
- •Refractive media opacity and miosis which effect fundus examination
- •Any eye of patient with active inflammation, such as conjunctivitis, keratitis, scleritis, uveitis and endophthalmitis
- •Choroidal neovascularization (CNV) for other reason, such as diabetic retinopathy, fundus angioid streaks, ocular histoplasmosis, pathologic myopia, trauma
- •The treatment of the eye
- •The studied eye received topical or grid photocoagulation more than twice or within 3 months before screening
Outcomes
Primary Outcomes
Frequency of ocular and systemic AEs (adverse events) and SAEs (serious adverse events) which are related to TK001
Time Frame: 6 weeks
Secondary Outcomes
- Frequency of subjects with anti-TK001 antibody(Up to Day 42)
- Best Corrected Visual Acuity (BCVA)(6 weeks)
- Area under the plasma concentration-time curve from time zero to infinity (AUCinf)(Up to Day 42)
- Maximum observed maximum plasma concentration (Cmax)(Up to Day 42)
- Area under the plasma concentration-time curve from time zero to time 't' where t is a defined time point after administration (AUC0-t)(Up to Day 42)
- Time to reach the maximum observed plasma concentration (Tmax)(Up to Day 42)