This study is designed for single-center, open-label, dose escalation phase I trial to evaluate the safety and tolerability of a single/multiple intravitreal injection of FB1001 in patients with APACG(Acute Primary Angle-Closure Glaucoma) or NAION(Nonarteritic Anterior Ischemic Optic Neuropathy).
After acute attack of APACG or NAION, patients are going to experience progression of visual field or visual acuity defects, even after IOP or inflammation control by diverse treatments. FB1001 is a recombinant humanized monoclonal antibody that protects and repairs the optic nerve, thereby delaying the progression of glaucoma and NAION. The main purpose of this study is to evaluate the safety and tolerability of FB1001 by single/multiple intravitreal injections to Acute Optic Neuropathy Patients. Pharmacokinetic profile through blood/Aqueous will be investigated and preliminary efficacy will be explored if possible. SAD(Single Ascending Dose) will consist of a maximum of 5 cohorts and each cohort will enroll 3 to 6 eligible patients. MAD(Multiple Ascending Dose) will consist of a maximum of 3 cohorts and each cohort will enroll 8 eligible patients. For each participant, the study will last up to about 12 weeks for SAD part, and 24 weeks for MAD part.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
59
Intravitreal (IVT) injection
Shanghai General Hospital, Shanghai Jiao Tong University
Shanghai, China
SAD phase: DLTs incidence
DLTs observed during the DLT observation period
Time frame: within 28 days after dosing
SAD phase: Incidence of Treatment-Emergent Adverse Events
The percentages of subjects experiencing AEs will be calculated.
Time frame: Baseline to 12 weeks
MAD phase: Incidence of Treatment-Emergent Adverse Events
The percentages of subjects experiencing AEs will be calculated.
Time frame: Baseline to 24 weeks
AUC0-t
The area under the drug-time curve from 0 to time t
Time frame: Baseline to end of study, SAD up to 12 weeks and MAD up to 24 weeks
AUC0-∞
The area under the curve at the time of 0-infinity
Time frame: Baseline to end of study, SAD up to 12 weeks and MAD up to 24 weeks
Cmax
The peak concentration
Time frame: Baseline to end of study, SAD up to 12 weeks and MAD up to 24 weeks
Tmax
The peak time
Time frame: Baseline to end of study, SAD up to 12 weeks and MAD up to 24 weeks
CL
Clearance rate
Time frame: Baseline to end of study, SAD up to 12 weeks and MAD up to 24 weeks
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t1/2
Half-life
Time frame: Baseline to end of study, SAD up to 12 weeks and MAD up to 24 weeks
MAD phase: Cmin,ss
The trough concentration in steady state
Time frame: Baseline to 24 weeks
MAD phase: Cavg,ss
The average concentration in steady state
Time frame: Baseline to 24 weeks
MAD phase: Rac
Accumulation Index
Time frame: Baseline to 24 weeks
Immunogenicity evaluation indicators
Positive rate of anti-drug antibody. (neutralizing antibody, if needed)
Time frame: Baseline to end of study, SAD up to 12 weeks and MAD up to 24 weeks
Preliminary biological effects and efficacy evaluation indicator 1
Anatomical changes in optic nerve head by OCT compared with baseline/fellow eyes
Time frame: Baseline to end of study, SAD up to 12 weeks and MAD up to 24 weeks
Preliminary biological effects and efficacy evaluation indicator 2
Changes in RNFL thickness by OCT with baseline/fellow eyes
Time frame: Baseline to end of study, SAD up to 12 weeks and MAD up to 24 weeks
Preliminary biological effects and efficacy evaluation indicator 3
Changes in GCC by OCT compared with baseline/fellow eyes
Time frame: Baseline to end of study, SAD up to 12 weeks and MAD up to 24 weeks
Preliminary biological effects and efficacy evaluation indicator 4
Changes in blood flow density of optic disc by OCTA with baseline/fellow eyes
Time frame: Baseline to end of study, SAD up to 12 weeks and MAD up to 24 weeks
Preliminary biological effects and efficacy evaluation indicator 5
Changes in blood flow density of macula by OCTA with baseline/fellow eyes
Time frame: Baseline to end of study, SAD up to 12 weeks and MAD up to 24 weeks
Preliminary biological effects and efficacy evaluation indicator 6
Changes in BCVA/Visual Field compared with baseline
Time frame: Baseline to end of study, SAD up to 12 weeks and MAD up to 24 weeks
Preliminary biological effects and efficacy evaluation indicator 7
Changes in P-VEP(pattern-visual evoked potential)compared with baseline
Time frame: Baseline to end of study, SAD up to 12 weeks and MAD up to 24 weeks
Preliminary biological effects and efficacy evaluation indicator 8
Changes in P-ERG compared with baseline
Time frame: Baseline to end of study, SAD up to 12 weeks and MAD up to 24 weeks