Neovascular Age-related Macular Degeneration
Conditions
Keywords
nAMD
Brief summary
The purpose of this Phase 1 study is comprised of multiple ascending-dose component (Part 1) and high concentration component (Part 2) to evaluate the safety, tolerability, pharmacokinetics, and efficacy of AM712 in patients with neovascular age- related macular degeneration (nAMD).
Detailed description
The Part 1 of study is a multicenter, open-label, sequentially, multiple ascending-dose study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of AM712 in subjects with nAMD. Subjects will be sequentially enrolled into different dose-level cohorts following the traditional 3+3 design until the maximally tolerated dose (MTD) or the maximally administered dose (MAD) has been reached. The Part 2 of study is a multicenter, open-label, sequential study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of AM712 in treatment-naïve patients with nAMD.
Interventions
BIOLOGICALAM712(ASKG712)
AM712 is a recombinant anti-VEGF humanized monoclonal antibody and Ang-2 antagonist peptide fusion protein, which has high specificity for the binding of VEGF-A and Ang-2.
Sponsors
AffaMed Therapeutics Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
The Phase 1 study is comprised of open-label multiple ascending-dose component (Part 1) and high concentration component (Part 2) to evaluate the safety, tolerability, pharmacokinetics, and efficacy of AM712 in patients with neovascular age- related macular degeneration (nAMD).
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects with 50 years of age or older 2. Active sub-foveal CNV lesion secondary to nAMD including juxta or extra-foveal lesions that partially affect the fovea 3. The area of CNV must occupy at least 50% of total lesion 4. Total lesion area ≤ 12 DA 5. ETDRS BCVA letter score measured at screening and baseline 6. Clear ocular media and adequate pupil dilation to permit good quality photographic imaging in study eye
Exclusion criteria
1. Any previous systemic anti-VEGF treatment 2. Any systemic treatment or therapy to treat neovascular AMD 3. Continuous use of systemic corticosteroids 4. Diseases that affect intravenous injection and venous blood sampling 5. Presence of CNV due to other causes, such as ocular histoplasmosis, trauma, multifocal choroiditis, angioid streaks, history of choroidal rupture, or pathologic myopia in study eye 6. History or any concurrent ocular condition which, in opinion of investigator, could either confound interpretation of efficacy and safety of IP or require medical or surgical intervention. 7. The area of fibrosis occupies ≥ 50% of total lesion area in study eye 8. Evidence of myopia degeneration, diagnosis supported by the axial length examination in study eye 9. History or any concurrent macular abnormality other than AMD in study eye 10. Current vitreous hemorrhage or history of vitreous hemorrhage in study eye 11. History of recurrent inflammation in study eye 12. History of treatment for nAMD 13. Subject having out of range laboratory values defined as: ALT or AST \> 2 x ULN, total bilirubin \> 1.5 x ULN Serum creatinine \> 1.5 x ULN, BUN \> 2 x ULN HbA1c \> 7.5% at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Any relevant safety observations derived from SD-OCT | 252 days | To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD) |
| Incidence of ocular adverse events (AEs) of the study eyes | 252 days | To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD) |
| Incidence of non-ocular AEs | 252 days | To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD) |
| Any relevant safety observations derived from BCVA | 252 days | To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean change from baseline in central subfield thickness as assessed by SD-OCT | 252 days | To evaluate the efficacy of AM712 in Subjects with nAMD |
| Proportion of patients with no intraretinal fluid, subretinal fluid, or pigment epithelial detachment as assessed by SD-OCT | 252 days | To evaluate the efficacy of AM712 in Subjects with nAMD |
| Mean change from baseline in BCVA (ETDRS) | 252 days | To evaluate the efficacy of AM712 in Subjects with nAMD |
| Proportion of patients gaining ≥ 15 letters from baseline BCVA | 252 days | To evaluate the efficacy of AM712 in Subjects with nAMD |
Countries
United States
Outcome results
None listed