Clinical trial NCT04331730: A Study to Assess the Efficacy and Safety of AKST4290 With Aflibercept in Patients With Newly Diagnosed nAMD
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neovascular Age-related Macular Degeneration
Keywords: Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Lead sponsor: Alkahest, Inc.
Sponsor class: INDUSTRY
First posted: 2020-04-02
Enrollment: 107
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Per the Early Treatment Diabetic Retinopathy Study (ETDRS) Testing Method
timeFrame: Baseline to Week 36
Secondary outcomes:
measure: Time to PRN Injection (Arms 1 and 2 Only)
timeFrame: Baseline to Week 36
measure: Median Number of Aflibercept Injections Received Beginning at Week 12
timeFrame: Week 12 to Week 36
measure: Percentage of Subjects With Best Corrected Visual Acuity (BCVA) Change of ≥ 15 Letters
timeFrame: Baseline to Week 36
measure: Mean Change in Central Subfield Thickness (CST) Compared With Control Through Week 12
timeFrame: Baseline to Week 12
measure: Number of Participants With Adverse Events Assessed by Intensity
timeFrame: Screening to Week 40
measure: Mean Change in Best Corrected Visual Acuity (BCVA) Per the Early Treatment Diabetic Retinopathy Study (ETDRS) Testing Method as Compared With Control
timeFrame: Week 12 to Week 36
measure: Time to the First Visit Where PRN Injection Criteria Are Met
timeFrame: Week 12 to the first visit meeting PRN injection criteria through week 36
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Retina-Vitreous Associates Medical Group
state: California
city: Saint Petersburg
country: United States
facility: Retina Vitreous Associates of FL
state: Florida
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Düsseldorf
country: Germany
facility: Internationale Innovative Ophthalmochirurgie GbR
city: Kiel
country: Germany
facility: nordBLICK Augenklinik Bellevue
city: Rheine
country: Germany
facility: Augentagesklinik Rheine
city: Budapest
country: Hungary
facility: Jahn Ferenc Dél-pesti Kórház (Jahn Ferenc South-Pest Hospital)
city: Budapest
country: Hungary
facility: Magyar Honvédség Egészségügyi Központ, Szemészeti Osztály (Medical Centre, Hungarian Defence Forces, Ophthalmology Department)
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház (Borsod-Abaúj-Zemplén County Hospital and University Teaching Hospital)
city: Pécs
country: Hungary
facility: GANGLION Orvosi Központ
city: Szekszárd
country: Hungary
facility: 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)
city: Bialystok
country: Poland
facility: Tęczówka (IRIS)
city: Bydgoszcz
country: Poland
facility: Specjalistyczny Ośrodek Okulistyczny Oculomedica (Specialized Eye Center Oculomedica)
city: Częstochowa
country: Poland
facility: PROVISUS Sp. z o.o.
city: Gdańsk
country: Poland
facility: Optimum Profesorskie Centrum Okulistyki
city: Kraków
country: Poland
facility: Centrum Medyczne Dietla 19 Sp zoo
city: Lublin
country: Poland
facility: Klinika Chirurgii Siatkówki i Ciała Szklistego Medical University in Lublin
city: Poznań
country: Poland
facility: Szpital św. Wojciecha
city: Suwałki
country: Poland
facility: ArtOptica Salon Okulistyczno
city: Tarnów
country: Poland
facility: Centrum Medyczne UNO-MED
city: Warsaw
country: Poland
facility: Central Clinical Hospital of the MSWiA
Study officials:
affiliation: Alkahest, Inc.
name: Alkahest Medical Monitor
role: STUDY_DIRECTOR
References: