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

• ClinicalTrials.gov Identifier: NCT04331730
• Recruitment Status: Completed
• First Posted: April 2, 2020
• Last Update Posted: October 11, 2021
• Sponsor: Alkahest, Inc.
• Information provided by (Responsible Party): Alkahest, Inc.

Tracking Information

• First Submitted Date: March 16, 2020
• First Posted Date: April 2, 2020
• Last Update Posted Date: October 11, 2021
• Actual Study Start Date: January 28, 2020
• Actual Primary Completion Date: August 19, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 1, 2020)

Mean change from baseline in Best Corrected Visual Acuity (BVCA) [ Time Frame: Screening to Week 40 ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 1, 2020)

• Time to first use of rescue therapy [ Time Frame: Baseline to Week 40 ]
  Time to first use of intravitreal aflibercept injection, as needed (AKST4290 Arms only). UNITS: days
• Mean number of aflibercept injections received [ Time Frame: Baseline to Week 36 ]
  Mean number of intravitreal aflibercept injections received. UNITS: number of injections
• Proportion of subjects with Best Corrected Visual Acuity (BCVA) change of ≥ 15 letters [ Time Frame: Screening to Week 40 ]
  Proportion of subjects with BCVA change of ≥ 15 letters at Week 36.
• Mean change in Central Subfield Thickness (CST) [ Time Frame: Screening to Week 40 ]
  Mean change in CST compared with control. UNITS: microns
• incidence and intensity of adverse events [ Time Frame: Screening to Week 40 ]
  Safety as assessed by incidence and intensity of adverse events.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: April 1, 2020)

• Mean change in Best Corrected Visual Acuity (BCVA) per the Early Treatment Diabetic Retinopathy Study (ETDRS) testing method [ Time Frame: Screening to Week 40 ]
  Mean change in BCVA per the ETDRS testing method in AKST4290 arms as compared with control.
• Changes in Low-Luminance Visual Acuity (LLVA) [ Time Frame: Baseline to Week 36 ]
  Changes in LLVA.
• Dose response as assessed by mean change in Best Corrected Visual Acuity (BCVA) and mean number of injections in [ Time Frame: 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.
• Changes in National Eye Institute Visual Function Questionnaire-39 (NEI-VFQ-39) [ Time Frame: Screening to Week 40 ]
  Scale is 0-100. Higher number corresponds to better visual function.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: 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
• 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 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Neovascular Age-related Macular Degeneration

Intervention

• Drug: AKST4290
  Oral AKST4290
• Drug: Placebo
  Oral placebo
• Drug: Aflibercept
  Aflibercept intravitreal injection

Study Arms

• Experimental: AKST4290 (800 mg) + Aflibercept
  Subjects will receive 400 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
  Interventions:

  • Drug: AKST4290
  • Drug: Aflibercept
• Experimental: AKST4290 (1600 mg) + Aflibercept
  Subjects will receive 800 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
  Interventions:

  • Drug: AKST4290
  • Drug: Aflibercept
• Placebo Comparator: Placebo + Aflibercept
  Subjects will receive placebo for 36 weeks, in combination with intravitreal aflibercept injection treatment
  Interventions:

  • Drug: Placebo
  • Drug: Aflibercept

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 7, 2021): 107
• Original Estimated Enrollment (submitted: April 1, 2020): 100
• Actual Study Completion Date: September 16, 2021
• Actual Primary Completion Date: August 19, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Hungary, Poland, United States

Administrative Information

• NCT Number: NCT04331730
• Other Study ID Numbers: AKST4290-205
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Alkahest, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Alkahest, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Alkahest, Inc.
• Verification Date: October 2021