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Neovascular Age-related Macular DegenerationPhase 2PHTHALO-205NCT04331730

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

A Phase 2 study testing AKST4290 and Aflibercept in people with Neovascular Age-related Macular Degeneration, run by Alkahest, Inc. at 21 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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). Read more about this study

Who is it for?
Ages 50 years and older
What is being tested?
AKST4290 and Aflibercept
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
107 participants
Where
21 sitesin 4 countries
Study dates
28 Jan 2020to 16 Sep 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

21 sites in 4 countries.

21 sites in 4 countries

Poland10 sites

  • Tęczówka (IRIS)

    Bialystok

  • Specjalistyczny Ośrodek Okulistyczny Oculomedica (Specialized Eye Center Oculomedica)

    Bydgoszcz

  • PROVISUS Sp. z o.o.

    Częstochowa

  • Optimum Profesorskie Centrum Okulistyki

    Gdansk

  • Centrum Medyczne Dietla 19 Sp zoo

    Krakow

  • Klinika Chirurgii Siatkówki i Ciała Szklistego Medical University in Lublin

    Lublin

  • Szpital św. Wojciecha

    Poznan

  • ArtOptica Salon Okulistyczno

    Suwałki

  • Centrum Medyczne UNO-MED

    Tarnów

  • Central Clinical Hospital of the MSWiA

    Warsaw

Other trials in Poland

Hungary5 sites

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

    Budapest

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

    Budapest

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

    Miskolc

  • GANGLION Orvosi Központ

    Pécs

  • 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

Other trials in Hungary

United States3 sites

  • Retina-Vitreous Associates Medical Group

    Beverly Hills, California, 90211

  • Sierra Eye Associates

    Reno, Nevada, 89502

  • Retina Vitreous Associates of FL

    St. Petersburg, Florida, 33711

Other trials in United States

Germany3 sites

  • Internationale Innovative Ophthalmochirurgie GbR

    Düsseldorf

  • nordBLICK Augenklinik Bellevue

    Kiel

  • Augentagesklinik Rheine

    Rheine

Other trials in Germany

About this study

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

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).

Read the 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.

Being tested
AKST4290, Placebo, Aflibercept
Keywords
Macular Degeneration, Retinal Degeneration, Retinal Diseases, Eye Diseases
Medical subject headings
Macular Degeneration, Retinal Degeneration, Retinal Diseases, Eye Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AKST4290Drug

    Oral AKST4290

  • PlaceboDrug

    Oral placebo

  • AfliberceptDrug

    Aflibercept intravitreal injection

Study groups in NCT04331730
Study groupRoleWhat they receive
AKST4290 (800 mg) + AfliberceptExperimentalSubjects will receive 400 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
Receives: Drug: AKST4290; Drug: Aflibercept
AKST4290 (1600 mg) + AfliberceptExperimentalSubjects will receive 800 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
Receives: Drug: AKST4290; Drug: Aflibercept
Placebo + AfliberceptPlacebo comparatorSubjects will receive placebo for 36 weeks, in combination with intravitreal aflibercept injection treatment
Receives: Drug: Placebo; Drug: Aflibercept

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to Week 36

Secondary outcomes (7)

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

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

    Measured: Baseline to Week 36

  2. 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

    Measured: Week 12 to Week 36

  3. 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.

    Measured: Baseline to Week 36

  4. 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

    Measured: Baseline to Week 12

  5. Number of Participants With Adverse Events Assessed by Intensity

    Number of Participants with Adverse Events categorized by intensity

    Measured: Screening to Week 40

  6. 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.

    Measured: Week 12 to Week 36

  7. 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

    Measured: Week 12 to the first visit meeting PRN injection criteria through week 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Apr 2020
  2. Study start28 Jan 2020
  3. Primary completion19 Aug 2021
  4. Study completion16 Sep 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
107 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04331730
Sponsor's protocol ID
AKST4290-205
Acronym
PHTHALO-205
Status last verified
Oct 2022
First submitted
16 Mar 2020
Last updated
26 Oct 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AKST4290 and Aflibercept in people with Neovascular Age-related Macular Degeneration, run by Alkahest, Inc. at 21 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Poland, Hungary, United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Per the Early Treatment Diabetic Retinopathy Study (ETDRS) Testing Method (time frame: Baseline to Week 36). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04331730.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2022.

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