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

Alkahest

Status and phase: Completed; Phase 2

Conditions: Neovascular Age-related Macular Degeneration

Treatments: Drug: Aflibercept; Drug: Placebo; Drug: AKST4290

Study type: Interventional

Funder types: Industry

Identifiers

NCT04331730

AKST4290-205

Details and patient eligibility

About

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).

Full 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.

Enrollment: 107 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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107 participants in 3 patient groups, including a placebo group

AKST4290 (800 mg) + Aflibercept

Experimental group

Description:

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

Treatment:

Drug: Aflibercept

Drug: AKST4290

AKST4290 (1600 mg) + Aflibercept

Experimental group

Description:

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

Treatment:

Drug: Aflibercept

Drug: AKST4290

Placebo + Aflibercept

Placebo Comparator group

Description:

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

Treatment:

Drug: Aflibercept

Drug: Placebo