PHTHALO-205: A Study to Assess the Efficacy and Safety of AKST4290 With Aflibercept in Patients With Newly Diagnosed nAMD

Sponsor
Alkahest, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT04331730
Collaborator
(none)
107
21
3
19.6
5.1
0.3

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 2

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 twice per day 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
107 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 28, 2020
Actual Primary Completion Date :
Aug 19, 2021
Actual Study Completion Date :
Sep 16, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: AKST4290 (800 mg) + Aflibercept

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

Drug: AKST4290
Oral AKST4290

Drug: Aflibercept
Aflibercept intravitreal injection

Experimental: AKST4290 (1600 mg) + Aflibercept

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

Drug: AKST4290
Oral AKST4290

Drug: Aflibercept
Aflibercept intravitreal injection

Placebo Comparator: Placebo + Aflibercept

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

Drug: Placebo
Oral placebo

Drug: Aflibercept
Aflibercept intravitreal injection

Outcome Measures

Primary Outcome Measures

  1. Mean change from baseline in Best Corrected Visual Acuity (BVCA) [Screening to Week 40]

    Mean change from baseline in BCVA per the Early Treatment Diabetic Retinopathy Study (ETDRS) testing method.

Secondary Outcome Measures

  1. Time to first use of rescue therapy [Baseline to Week 40]

    Time to first use of intravitreal aflibercept injection, as needed (AKST4290 Arms only). UNITS: days

  2. Mean number of aflibercept injections received [Baseline to Week 36]

    Mean number of intravitreal aflibercept injections received. UNITS: number of injections

  3. Proportion of subjects with Best Corrected Visual Acuity (BCVA) change of ≥ 15 letters [Screening to Week 40]

    Proportion of subjects with BCVA change of ≥ 15 letters at Week 36.

  4. Mean change in Central Subfield Thickness (CST) [Screening to Week 40]

    Mean change in CST compared with control. UNITS: microns

  5. incidence and intensity of adverse events [Screening to Week 40]

    Safety as assessed by incidence and intensity of adverse events.

Other Outcome Measures

  1. Mean change in Best Corrected Visual Acuity (BCVA) per the Early Treatment Diabetic Retinopathy Study (ETDRS) testing method [Screening to Week 40]

    Mean change in BCVA per the ETDRS testing method in AKST4290 arms as compared with control.

  2. Changes in Low-Luminance Visual Acuity (LLVA) [Baseline to Week 36]

    Changes in LLVA.

  3. Dose response as assessed by mean change in Best Corrected Visual Acuity (BCVA) and mean number of injections in [Screening to Week 40]

    Dose response as assessed by mean change in BCVA and mean number of injections in all treatment arms by study visit.

  4. Changes in National Eye Institute Visual Function Questionnaire-39 (NEI-VFQ-39) [Screening to Week 40]

    Scale is 0-100. Higher number corresponds to better visual function.

Eligibility Criteria

Criteria

Ages Eligible for Study:
50 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
  • Men and women with newly diagnosed active CNV secondary to 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 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.

  • CST thickness ≥ 250 microns on SD-OCT (exclusive of subretinal pigment epithelial fluid, inclusive of SRF).

  • Presence of SRF and/or IRF on SD-OCT.

  • Total lesion size not greater than 12 disc areas (30.48 mm2) (1 disc area = 2.54 mm2) on FA.

  • If present, subretinal hemorrhage must comprise < 50% of the total lesion area on FA, SD-OCT, or FP/FAF.

  • No subfoveal fibrosis or atrophy on FA, SD-OCT, or FP/FAF.

  • Active CNV membranes with subfoveal leakage or juxtafoveal leakage too close for laser photocoagulation.

  • BCVA 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 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 reading, subjects with a risk of QT prolongation.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Retina-Vitreous Associates Medical Group Beverly Hills California United States 90211
2 Retina Vitreous Associates of FL Saint Petersburg Florida United States 33711
3 Sierra Eye Associates Reno Nevada United States 89502
4 Internationale Innovative Ophthalmochirurgie GbR Düsseldorf Germany
5 nordBLICK Augenklinik Bellevue Kiel Germany
6 Augentagesklinik Rheine Rheine Germany
7 Jahn Ferenc Dél-pesti Kórház (Jahn Ferenc South-Pest Hospital) Budapest Hungary
8 Magyar Honvédség Egészségügyi Központ, Szemészeti Osztály (Medical Centre, Hungarian Defence Forces, Ophthalmology Department) Budapest Hungary
9 Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház (Borsod-Abaúj-Zemplén County Hospital and University Teaching Hospital) Miskolc Hungary
10 GANGLION Orvosi Központ Pécs Hungary
11 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
12 Tęczówka (IRIS) Bialystok Poland
13 Specjalistyczny Ośrodek Okulistyczny Oculomedica (Specialized Eye Center Oculomedica) Bydgoszcz Poland
14 PROVISUS Sp. z o.o. Częstochowa Poland
15 Optimum Profesorskie Centrum Okulistyki Gdańsk Poland
16 Centrum Medyczne Dietla 19 Sp zoo Kraków Poland
17 Klinika Chirurgii Siatkówki i Ciała Szklistego Medical University in Lublin Lublin Poland
18 Szpital św. Wojciecha Poznań Poland
19 ArtOptica Salon Okulistyczno Suwałki Poland
20 Centrum Medyczne UNO-MED Tarnów Poland
21 Central Clinical Hospital of the MSWiA Warsaw Poland

Sponsors and Collaborators

  • Alkahest, Inc.

Investigators

  • Study Director: Alkahest Medical Monitor, Alkahest, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Alkahest, Inc.
ClinicalTrials.gov Identifier:
NCT04331730
Other Study ID Numbers:
  • AKST4290-205
First Posted:
Apr 2, 2020
Last Update Posted:
Oct 11, 2021
Last Verified:
Oct 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Alkahest, Inc.
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 11, 2021