Age-related macular degeneration MedDRA version: 20.0 Level: LLT Classification code 10075568 Term: Wet age-related macular degeneration System Organ Class: 100000004853
Conditions
Interventions
Product Name: AKST4290
Product Code: AKST4290
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: AKST4290
CAS Number: 1251528-23-0
Current Sponsor code: AKST4290
Concentration unit: mg milli
Sponsors
Alkahest, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women with active CNV secondary to AMD in 1 eye, as diagnosed by a retinal specialist, with all the following characteristics and ophthalmic inclusion criteria applied to the contralateral eye (study eye), as assessed by a reader. a. No active CNV secondary to AMD. b. No geographic atrophy. c. No previous treatment for AMD. d. Ametropy =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Previous participation in any studies of investigational drugs within 1 month preceding Screening. 2. Any form of macular degeneration that is not age-related (e.g., Best’s disease, Stargardt’s disease, Sorsby’s disease). 3. Additional eye disease in either eye that could compromise BCVA (i.e., uncontrolled glaucoma (intraocular pressure > 24) with visual field loss, clinically significant diabetic edema, history of ischemic optic neuropathy or retinal vascular occlusion, vitreomacular traction, monocular vision, high myopia > 8 diopters, or genetic disorders such as retinitis pigmentosa). 4. Anterior segment and vitreous abnormalities in the either eye that would preclude adequate visualization with fundus photography or SD-OCT. 5. Intraocular surgery in either eye within 3 months prior to screening. 6. Aphakia or total absence of the posterior capsule (yttrium-aluminum-garnet laser capsulotomy is permitted in an eye with a posterior chamber intraocular lens if performed a minimum of 1 month prior to enrollment) in the study eye. 7. Known allergy to fluorescein sodium. 8. Current or planned use of medications known to be toxic to the retina, lens, or optic nerve. (e.g., desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol). 9. Medical history or condition: a. Uncontrolled diabetes mellitus, with hemoglobin A1c (HbA1c) > 8%. b. Myocardial infarction or stroke within 12 months of screening. c. Active bleeding disorder. d. Concomitant use of Vitamin K antagonists or new oral anticoagulants. e. Major surgery within 1 month of screening or planned within the study period. f. Hepatic impairment. g. Uncontrolled systemic arterial hypertension. h. Positive test result for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) at Screening (Visit 1). 10. Prior treatment within 4 weeks of Screening (Visit 1) or planned use of potent cytochrome P450 3A4/5 (CYP3A4/5) or P-glycoprotein (P-gp) inhibitors or inducers during the study. 11. Planned concomitant use of CYP3A4/5 or P-gp substrates that have a narrow therapeutic index (e.g., digoxin). 12. Planned concomitant use of CYP3A4/5 sensitive substrates, such as fentanyl. 13. Planned concomitant use of drugs with a narrow therapeutic window that are metabolized predominantly by CYP2C8 (e.g., carbamazepine), or are CYP2C8 sensitive substrates, such as dasabuvir and repaglinide. 14. Planned concomitant use of organic anion transporter 3 (OAT3) substrates, such as methotrexate and pravastatin. 15. Patients with renal impairment (estimated glomerular filtration rate [GFR] = 60) who have planned concomitant use of OCT2 substrates with a narrow therapeutic index or OCT2 inhibitors (e.g. metformin). 16. Use of any nonselective monoamine oxidase inhibitors (MAOI) (MAOI-B treatment is acceptable). 17. Use of systemic corticosteroids (> 10 mg prednisone or equivalent/day) within 14 days of first dose of study agent or known diseases which could require the use of systemic corticosteroids within the study period. 18. Use of intravitreal or implanted corticosteroids: a. Dexamethasone (Ozurdex®) or triamcinolone within 6 months prior to screening. b. Fluocinolone (Retisert® or Iluvien®) within 48 months prior to screening. 19. Patients with clinically relevant, abnormal screening hematology, blood chemistry, or urinalysis test results, if the abnormality defines a significant disease as defined in o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effects of a 4-week, oral b.i.d. dosing regimen of AKST4290 on choroidal blood flow (ChBF) in the contralateral eye in subjects with unilateral neovascular age-related macular degeneration (nAMD);Secondary Objective: Secondary Objectives: To assess central retinal thickness (CRT), retinal nerve fiber layer thickness (RNFLT), retinal microcirculation, RVD, ROS, best corrected visual acuity (BCVA), intraocular pressure (IOP), and ocular perfusion pressure (OPP) in both eyes. Exploratory Objectives: To assess biomarkers and pharmacokinetics (PK) on blood and plasma samples.;Primary end point(s): Mean change in ChBF in the contralateral (study) eye measured using laser Doppler flowmetry (LDF).;Timepoint(s) of evaluation of this end point: Before treatment start and after 4 weeks treatment. 2 weeks after end of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): o Mean changes in central retinal thickness (CRT) and retinal nerve fiber layer thickness (RNFLT) as measured by SD-OCT. o Mean change in best corrected visual acuity (BCVA) as measured by the ETDRS chart method. o Mean changes on intraocular pressure (IOP) and ocular perfusion pressure (OPP). o Mean changes in retinal vessel diameters (RVD) and retinal oxygen saturation (ROS) as measured by dynamic vessel analyzer (DVA) and fundus photography. o Mean change in retinal microcirculation as measured by OCT angiography (OCT-A). o Mean changes in systemic hemodynamics including SBP, DBP, and HR. o Incidence of AEs. ;Timepoint(s) of evaluation of this end point: Before treatment start and after 4 weeks treatment. 2 weeks after end of treatment | — |
Countries
Austria
Contacts
Public ContactDepartment of Clinical Pharmacology
Medical University of Vienna
Outcome results
None listed