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

NCT04331730 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AKST4290-205
• Study Type: interventional
• Target: 107
• Locations: 4 countries
• Sites: 21

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).

Conditions

Neovascular Age-related Macular Degeneration

Keywords

Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Time to PRN Injection (Arms 1 and 2 Only)

  Baseline to Week 36

• Median Number of Aflibercept Injections Received Beginning at Week 12

  Week 12 to Week 36

• Percentage of Subjects With Best Corrected Visual Acuity (BCVA) Change of ≥ 15 Letters

  Baseline to Week 36

• Mean Change in Central Subfield Thickness (CST) Compared With Control Through Week 12

  Baseline to Week 12

• Number of Participants With Adverse Events Assessed by Intensity

  Screening to Week 40

Study Arms (3)

AKST4290 (800 mg) + Aflibercept

EXPERIMENTAL

Subjects will receive 400 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment

Drug: AKST4290; Drug: Aflibercept

AKST4290 (1600 mg) + Aflibercept

EXPERIMENTAL

Subjects will receive 800 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment

Drug: AKST4290; Drug: Aflibercept

Placebo + Aflibercept

PLACEBO COMPARATOR

Subjects will receive placebo for 36 weeks, in combination with intravitreal aflibercept injection treatment

Drug: Placebo; Drug: Aflibercept

Interventions

AKST4290 DRUG

Oral AKST4290

AKST4290 (1600 mg) + Aflibercept; AKST4290 (800 mg) + Aflibercept

Placebo DRUG

Oral placebo

Placebo + Aflibercept

Aflibercept DRUG

Aflibercept intravitreal injection

AKST4290 (1600 mg) + Aflibercept; AKST4290 (800 mg) + Aflibercept; Placebo + Aflibercept

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alkahest, Inc.: lead

Study Sites (21)

Retina-Vitreous Associates Medical Group

Beverly Hills, California, 90211, United States

Location

Retina Vitreous Associates of FL

St. Petersburg, Florida, 33711, United States

Location

Sierra Eye Associates

Reno, Nevada, 89502, United States

Location

Internationale Innovative Ophthalmochirurgie GbR

Düsseldorf, Germany

Location

nordBLICK Augenklinik Bellevue

Kiel, Germany

Location

Augentagesklinik Rheine

Rheine, Germany

Location

Jahn Ferenc Dél-pesti Kórház (Jahn Ferenc South-Pest Hospital)

Budapest, Hungary

Location

Magyar Honvédség Egészségügyi Központ, Szemészeti Osztály (Medical Centre, Hungarian Defence Forces, Ophthalmology Department)

Budapest, Hungary

Location

Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház (Borsod-Abaúj-Zemplén County Hospital and University Teaching Hospital)

Miskolc, Hungary

Location

GANGLION Orvosi Központ

Pécs, Hungary

Location

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, Hungary

Location

Tęczówka (IRIS)

Bialystok, Poland

Location

Specjalistyczny Ośrodek Okulistyczny Oculomedica (Specialized Eye Center Oculomedica)

Bydgoszcz, Poland

Location

PROVISUS Sp. z o.o.

Częstochowa, Poland

Location

Optimum Profesorskie Centrum Okulistyki

Gdansk, Poland

Location

Centrum Medyczne Dietla 19 Sp zoo

Krakow, Poland

Location

Klinika Chirurgii Siatkówki i Ciała Szklistego Medical University in Lublin

Lublin, Poland

Location

Szpital św. Wojciecha

Poznan, Poland

Location

ArtOptica Salon Okulistyczno

Suwałki, Poland

Location

Centrum Medyczne UNO-MED

Tarnów, Poland

Location

Central Clinical Hospital of the MSWiA

Warsaw, Poland

Location

MeSH Terms

Conditions

Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary

Results Point of Contact

• Title: Head of Communications
• Organization: Alkahest, Inc.

trials@alkahest.com

(650) 801-0474

Study Officials

• Alkahest Medical Monitor

  Alkahest, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2020
• First Posted: April 2, 2020
• Study Start: January 28, 2020
• Primary Completion: August 19, 2021
• Study Completion: September 16, 2021
• Last Updated: October 26, 2022
• Results First Posted: October 26, 2022

Record last verified: 2022-10

Locations

US (3); DE (3); HU (5); PL (10)