Evaluate the Therapeutic Effects and Safety of ALK4290 in Patients With Refractory Wet Age-Related Macular Degeneration

A Single Arm Open-Label Study to Evaluate the Therapeutic Effects and Safety of a 6-Week Treatment Regimen of ALK4290 in Patients With Refractory Wet Age-Related Macular Degeneration (wAMD)

This study will evaluate the therapeutic effects and safety of 800 mg ALK4290 administered daily over a 6-week dosing period in subjects with refractory wet age-related macular degeneration (wAMD).

Study Overview

• Status: Completed
• Conditions: Wet Age-related Macular Degeneration
• Intervention / Treatment: Drug: ALK4290

Detailed Description

This study is designed to investigate the potential therapeutic effects and safety of oral ALK4290 administered 800 mg daily over a 6-week dosing period as measured by Best Corrected Visual Acuity (BCVA) in subjects with refractory wAMD (i.e., following monthly intravitreal [IVT] anti-VEGF therapy for at least 3 months in the study eye).

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary
    • Jahn Ferenc South-Pest Hospital and Clinic
  • Miskolc, Hungary
    • Borsod-Abaúj-Zemplén County Hospital and Teaching Hospital
  • Nyíregyháza, Hungary
    • Szabolcs-Szatmar-Bereg County Hospital and University Hospital
  • Szeged, Hungary
    • University of Szeged Faculty of Medicine
  • Szombathely, Hungary
    • Markusovszky University Teaching Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women with refractory active CNV secondary to AMD, diagnosed by a retinal specialist with all the following characteristics and ophthalmic inclusion criteria applied to the study eye:

  • Persistent exudation of SRF and IRF as documented by SD-OCT and absence of improvement in visual acuity following monthly IVT anti-VEGF therapy of at least 3 months; subject must have received their last IVT anti-VEGF injection 30 to 90 days prior to the initial screening visit
  • Central subfield retinal thickness ≥ 250 microns on SD-OCT (exclusive of subretinal pigment epithelial fluid, inclusive of SRF)
  • Total lesion size not greater than 12 disc areas on FA
  • If present, subretinal hemorrhage must comprise < 50% of the total lesion area on FA
  • No subfoveal fibrosis or atrophy on FA
• BCVA letter score, as measured by ETDRS in the study eye, between 70 and 24 letters, inclusive, at screening
• Patients 50 years of age or older at screening visit 1
• Body mass index (BMI) between18 and ≤ 40 at screening visit 1
• Female subjects must not be pregnant or breastfeeding. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry. 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
• Signed informed consent consistent with ICH-GCP guidelines and local legislation prior to participation in the trial, which includes medication washout and restrictions

Exclusion Criteria:

• Treatment with IVT anti-VEGF therapy within 30 days preceding screening visit in the study eye and/or planned concomitant IVT anti-VEGF treatment in the fellow eye during the study period
• Previous participation in any studies of investigational drugs within 1 month preceding screening visit
• Any form of macular degeneration that is not age-related (e.g., Best's disease, Stargardt's disease, Sorsby's disease, etc.)
• Additional eye disease in the study eye that could compromise BCVA (i.e., uncontrolled glaucoma (intraocular pressure > 24) with visual field loss, clinically significant diabetic maculopathy, history of ischemic optic neuropathy or retinal vascular occlusion, vitreomacular traction, monocular vision, or genetic disorders such as retinitis pigmentosa; high myopia > 8 diopters)
• Anterior segment and vitreous abnormalities in the study eye that would preclude adequate observation with fundus photography/FA or SD-OCT
• Intraocular surgery in the study eye within 3 months prior to screening
• Aphakia or total absence of the posterior capsule (yttrium aluminum garnet (YAG) laser capsulotomy permitted, a minimum of 1 month prior to enrollment) in the study eye

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Active; ALK4290 800 mg daily	Drug: ALK4290; ALK4290 400 mg tablet twice a day; Other Names: AKST4290; BI 144807

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Corrected Visual Acuity (BCVA)	Mean changes in BCVA as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) testing method. The ETDRS chart assesses changes in vision based on the number of letters correctly read by the subject	Baseline to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-emergent Adverse Events (Safety)	Treatment-emergent adverse events identified by the Common Terminology Criteria for Adverse Events (CTCAE v4.03)	Baseline to 10 weeks

Collaborators and Investigators

• Sponsor: Alkahest, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 20, 2018
• Primary Completion (ACTUAL): November 29, 2018
• Study Completion (ACTUAL): November 29, 2018

Study Registration Dates

• First Submitted: May 15, 2018
• First Submitted That Met QC Criteria: June 13, 2018
• First Posted (ACTUAL): June 15, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 22, 2020
• Last Update Submitted That Met QC Criteria: November 30, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Refractory wAMD
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration
• Other Study ID Numbers: ALK4290-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes