A clinical study to assess the effect of AKST4290 in patients with age-related macular degeneratio

Phase 1

• Conditions: Age-related macular degeneration; MedDRA version: 20.0Level: LLTClassification code 10075568Term: Wet age-related macular degenerationSystem Organ Class: 100000004853; Therapeutic area: Diseases [C] - Eye Diseases [C11]

• Registration Number: EUCTR2019-002821-31-AT
• Lead Sponsor: Alkahest, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-07-15
• Last Update Posted: 20 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 15

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 2.Patients 50 years of age or older at Screening (Visit 1).
3.Body mass index (BMI) between 18 and = 40 at Screening (Visit 1).
4.Female subjects must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at Screening (Visit 1), and the last treatment visit (Visit 3). WOCBP and men must agree to use highly effective contraception (Clinical Trial Facilitation Group 2014) prior to study entry. A woman is considered of childbearing potential following menarche and until becoming postmenopausal (no menses for at least 2 years without an alternative cause). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in the study, she should inform her treating physician immediately.
5.Signed informed consent consistent with ICH-GCP guidelines and local legislation prior to participation in the trial, which includes medication washout and restrictions.
6.Must agree to be on stable doses of medications that may impact ChBF (complete listing of these medications will be provided in the Investigator Site File (ISF).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.<br><br>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. <br>2 weeks after end of treatment

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): oMean changes in central retinal thickness (CRT) and retinal nerve fiber layer thickness (RNFLT) as measured by SD-OCT. <br>oMean change in best corrected visual acuity (BCVA) as measured by the ETDRS chart method.<br>oMean changes on intraocular pressure (IOP) and ocular perfusion pressure (OPP).<br>oMean changes in retinal vessel diameters (RVD) and retinal oxygen saturation (ROS) as measured by dynamic vessel analyzer (DVA) and fundus photography.<br>oMean change in retinal microcirculation as measured by OCT angiography (OCT-A).<br>oMean changes in systemic hemodynamics including SBP, DBP, and HR.<br>oIncidence of AEs.<br><br>;Timepoint(s) of evaluation of this end point: Before treatment start and after 4 weeks treatment. <br>2 weeks after end of treatment