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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04331730
Recruitment Status : Completed
First Posted : April 2, 2020
Last Update Posted : October 11, 2021
Sponsor:
Information provided by (Responsible Party):
Alkahest, Inc.

Tracking Information
First Submitted Date  ICMJE March 16, 2020
First Posted Date  ICMJE April 2, 2020
Last Update Posted Date October 11, 2021
Actual Study Start Date  ICMJE January 28, 2020
Actual Primary Completion Date August 19, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE 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  ICMJE A Study to Assess the Efficacy and Safety of AKST4290 With Aflibercept in Patients With Newly Diagnosed nAMD
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Neovascular Age-related Macular Degeneration
Intervention  ICMJE
  • Drug: AKST4290
    Oral AKST4290
  • Drug: Placebo
    Oral placebo
  • Drug: Aflibercept
    Aflibercept intravitreal injection
Study Arms  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 7, 2021)
107
Original Estimated Enrollment  ICMJE
 (submitted: April 1, 2020)
100
Actual Study Completion Date  ICMJE September 16, 2021
Actual Primary Completion Date August 19, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Hungary,   Poland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04331730
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Current Responsible Party Alkahest, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Alkahest, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Alkahest Medical Monitor Alkahest, Inc.
PRS Account Alkahest, Inc.
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP