A Study to Assess the Efficacy and Safety of AKST4290 With Aflibercept in Patients With Newly Diagnosed nAMD

Neovascular Age-related Macular Degeneration Clinical Trial

— PHTHALO-205  

Official title:

A Double-Masked, Placebo-Controlled, Dose Ranging Study to Evaluate the Efficacy of Oral AKST4290 With Loading Doses of Aflibercept in Patients With Newly Diagnosed Neovascular Age-Related Macular Degeneration

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04331730
• Other study ID #: AKST4290-205
• Status: Completed
• Phase: Phase 2
• Start date: January 28, 2020
• Est. completion date: September 16, 2021

Study information

• Verified date: October 2022
• Source: Alkahest, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy and safety of AKST4290 in combination with aflibercept injections in subjects with newly diagnosed neovascular age-related macular degeneration (nAMD).

Description:

This is a randomized, double-masked, placebo-controlled, dose-ranging, multicenter study to assess the efficacy and safety of AKST4290 administered orally at 400 mg b.i.d. or 800 mg b.i.d. in combination with intravitreal aflibercept injections (IAI), in subjects with newly diagnosed neovascular age-related macular degeneration (nAMD) who are naïve to treatment with anti-vascular endothelial growth factor (anti-VEGF) medications in the study eye. Subjects will be treated with AKST4290 800 mg daily, 1600 mg daily, or placebo for a total of 36 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 107
• Est. completion date: September 16, 2021
• Est. primary completion date: August 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Key Inclusion Criteria:

• Men and women with newly diagnosed active Choroidal Neovascularization (CNV) secondary to Age-Related Macular Degeneration (AMD), diagnosed by a retinal specialist with all the following characteristics and ophthalmic inclusion criteria applied to the study

eye, as assessed by a central reader:

• Has been examined by a retinal specialist and found to be eligible to receive Intravitreal Aflibercept Injection (IAI) in the study eye.
• No prior treatment for Neovascular Age-Related Macular Degeneration (nAMD) in the study eye.
• Study eye has not undergone pars plana vitrectomy or glaucoma filtering surgery.
• Participation in studies of investigational drugs must have been discontinued within 30 days or 5 half-lives of the drug (whichever was longer) prior to screening.
• Central subfield thickness (CST) thickness = 250 microns on SD-OCT (spectral domain OCT) (exclusive of subretinal pigment epithelial fluid, inclusive of SRF).
• Presence of SRF (subretinal fluid) and/or IRF (intraretinal fluid) on SD-OCT.
• Total lesion size not greater than 12 disc areas (30.48 mm2) (1 disc area = 2.54 mm2) on FA (fluorescein angiography).
• If present, subretinal hemorrhage must comprise < 50% of the total lesion area on FA, SD-OCT, or FP/FAF (fundus photography/fundus autofluorescence).
• No subfoveal fibrosis or atrophy on FA, SD-OCT, or FP/FAF.
• Active CNV (choroidal neovascularization) membranes with subfoveal leakage or juxtafoveal leakage too close for laser photocoagulation.
• BCVA (Best Corrected Visual Acuity) in the study eye between 70 and 24 letters inclusive.
• Body mass index (BMI) between (and inclusive of) 18 and 40 at screening.

Key Exclusion Criteria:

• Participation in studies of investigational drugs within 30 days or 5 half-lives of the drug (whichever was longer) prior to screening.
• Known hypersensitivity to the active substance or any of the excipients of AKST4290 or aflibercept.
• Active or suspected ocular or periocular infection and/or active, severe intraocular inflammation.
• Any form of macular degeneration that is not age-related (e.g., Best's disease, Stargardt's disease, Sorsby's disease).
• Additional disease in the study eye that could compromise BCVA (i.e., uncontrolled glaucoma (IOP >24) with visual field loss, clinically significant diabetic macular edema, history of ischemic optic neuropathy or retinal vascular occlusion, vitreomacular traction, high myopia > 6 diopters, or genetic disorders such as retinitis pigmentosa).
• Presence of RPE (Retinal Pigment Epithelium) tears or rips in the study eye.
• Anterior segment and vitreous abnormalities in the study eye that would preclude adequate visualization with FP/FAF, 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 in an eye with a posterior chamber intraocular lens if performed a minimum of 1 month prior to enrollment) in the study eye.
• Known allergy to fluorescein sodium.
• Significant alcohol or drug abuse within past 2 years.
• Based on ECG (electrocardiogram) reading, subjects with a risk of QT prolongation. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-related Macular Degeneration
• Wet Macular Degeneration

Intervention

Drug:
• AKST4290
Oral AKST4290
• Placebo
Oral placebo
• Aflibercept
Aflibercept intravitreal injection

Locations

Country	Name	City	State
Germany	Internationale Innovative Ophthalmochirurgie GbR	Düsseldorf
Germany	nordBLICK Augenklinik Bellevue	Kiel
Germany	Augentagesklinik Rheine	Rheine
Hungary	Jahn Ferenc Dél-pesti Kórház (Jahn Ferenc South-Pest Hospital)	Budapest
Hungary	Magyar Honvédség Egészségügyi Központ, Szemészeti Osztály (Medical Centre, Hungarian Defence Forces, Ophthalmology Department)	Budapest
Hungary	Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház (Borsod-Abaúj-Zemplén County Hospital and University Teaching Hospital)	Miskolc
Hungary	GANGLION Orvosi Központ	Pécs
Hungary	Szegedi Tudományegyetem Általános Orvostudományi Kar, Szent-Györgyi Albert Klinikai Központ, Szemészeti Klinika, (University of Szeged Faculty of Medicine, Albert-Szent Gyorgyi Health Care, Department of Ophthalmology)	Szekszárd
Poland	Teczówka (IRIS)	Bialystok
Poland	Specjalistyczny Osrodek Okulistyczny Oculomedica (Specialized Eye Center Oculomedica)	Bydgoszcz
Poland	PROVISUS Sp. z o.o.	Czestochowa
Poland	Optimum Profesorskie Centrum Okulistyki	Gdansk
Poland	Centrum Medyczne Dietla 19 Sp zoo	Kraków
Poland	Klinika Chirurgii Siatkówki i Ciala Szklistego Medical University in Lublin	Lublin
Poland	Szpital sw. Wojciecha	Poznan
Poland	ArtOptica Salon Okulistyczno	Suwalki
Poland	Centrum Medyczne UNO-MED	Tarnów
Poland	Central Clinical Hospital of the MSWiA	Warsaw
United States	Retina-Vitreous Associates Medical Group	Beverly Hills	California
United States	Sierra Eye Associates	Reno	Nevada
United States	Retina Vitreous Associates of FL	Saint Petersburg	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Alkahest, Inc.

Countries where clinical trial is conducted

United States,  Germany,  Hungary,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Per the Early Treatment Diabetic Retinopathy Study (ETDRS) Testing Method	Mean change from baseline in Best Corrected Visual Acuity (BCVA) per the Early Treatment Diabetic Retinopathy Study (ETDRS) testing method. BCVA will be assessed using ETDRS charts at 4 meters initial testing distance and assessed in both eyes. Score range is 0 to 93. A higher score indicates better vision.	Baseline to Week 36
Secondary	Time to PRN Injection (Arms 1 and 2 Only)	Time to first use of intravitreal aflibercept injection, as needed (AKST4290 Arms only). UNITS: weeks.	Baseline to Week 36
Secondary	Median Number of Aflibercept Injections Received Beginning at Week 12	Median number of injections received beginning at Week 12 as a rate. UNITS: number of injections per week from Week 12	Week 12 to Week 36
Secondary	Percentage of Subjects With Best Corrected Visual Acuity (BCVA) Change of = 15 Letters	Percentage of subjects with Best Corrected Visual Acuity (BCVA) change of = 15 letters at Week 36.	Baseline to Week 36
Secondary	Mean Change in Central Subfield Thickness (CST) Compared With Control Through Week 12	Mean change in Central Subfield Thickness (CST) compared with control through Week 12. UNITS: micrometre	Baseline to Week 12
Secondary	Number of Participants With Adverse Events Assessed by Intensity	Number of Participants with Adverse Events categorized by intensity	Screening to Week 40
Secondary	Mean Change in Best Corrected Visual Acuity (BCVA) Per the Early Treatment Diabetic Retinopathy Study (ETDRS) Testing Method as Compared With Control	Mean change in Best Corrected Visual Acuity (BCVA) letter score per the Early Treatment Diabetic Retinopathy Study (ETDRS) testing method from Week 12 as compared to control at Week 36. BCVA will be assessed using ETDRS charts at 4 meters initial testing distance and assessed in both eyes. Score range is 0 to 93. A higher score indicates better vision.	Week 12 to Week 36
Secondary	Time to the First Visit Where PRN Injection Criteria Are Met	Time to the first visit where PRN injection criteria are met starting at Week 12 will be calculated in weeks as the first date where PRN injection criteria are first met minus the date of first dose of study drug plus one, divided by seven. Subjects who do not experience the event of interest (meet the criteria for PRN IAI) while on the study will be censored at their last visit completed through Week 36. Units: weeks	Week 12 to the first visit meeting PRN injection criteria through week 36