search
Back to results

Study of AR-14034 in Participants With Neovascular Age-Related Macular Degeneration (nAMD) (NOVA-1)

Primary Purpose

Neovascular Age-related Macular Degeneration (nAMD)

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
AR-14034 SR implant lower dose
Aflibercept Injection
Sham procedure
AR-14034 SR implant higher dose
Sponsored by
Aerie Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neovascular Age-related Macular Degeneration (nAMD) focused on measuring nAMD, retina, eyes, ophthalmology

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria [Stage 1 and Stage 2]: Presence of an active choroidal neovascularization (CNV) lesion secondary to age-related macular degeneration (AMD); Best corrected visual acuity (BCVA) between 80 and 35 letters (20/25 to 20/200 Snellen equivalent) in the study eye; BCVA greater than 34 letters (approximately 20/200 Snellen equivalent) in the non-study eye; Media clarity and pupillary dilation in the study eye sufficient for all planned study procedures; Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol; Other protocol-specified inclusion criteria may apply. [Stage 1]: Greater than or equal to 3 and less than or equal to 6 prior treatments of an ocular anti-VEGF medication within the 8 months prior to Screening in the study eye, with demonstrated anatomic response, as assessed by the Investigator. [Stage 2]: Treatment-naïve, or initial diagnosis of exudative neovascular age-related macular degeneration (nAMD) in the study eye within 9 months before Screening. Key Exclusion Criteria [Stage 1 and Stage 2]: History or current ocular disease in the study eye other than nAMD, that, might require medical or surgical intervention during the study; Structural damage to the macula that is likely to preclude improvement in visual acuity in the study eye after resolution of the nAMD; Any active intraocular or periocular infection or active intraocular inflammation; Treatment with ocular anti-VEGF product within 28-days before Week -1 [Stage 1] or Baseline [Stage 2]; Uncontrolled glaucoma in the study eye; Uncontrolled blood pressure; Females of child-bearing potential who are pregnant, intending to become pregnant, nursing, or who are not willing to use an acceptable form of contraception for the duration of the study; Other protocol-specified exclusion criteria may apply.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Active Comparator

    Arm Label

    Cohort 1 (Stage 1)

    Cohort 2 (Stage 1)

    AR-14034 SR lower dose (Stage 2)

    AR-14034 SR higher dose (Stage 2)

    Aflibercept (Stage 2)

    Arm Description

    One intravitreal (IVT) injection of aflibercept 2 mg at Week -1 and one IVT insertion of AR-14034 SR lower dose at Baseline. Up to one retreatment with AR-14034 SR will be administered between Weeks 4 and 36 according to protocol-specified disease activity criteria.

    One IVT injection of aflibercept 2 mg at Week -1 and one IVT insertion of AR-14034 SR higher dose at Baseline. Up to one retreatment with AR-14034 SR will be administered between Weeks 4 and 36 according to protocol-specified disease activity criteria.

    One IVT injection of aflibercept 2 mg at Baseline, Week 4, and Week 8, with one IVT insertion of AR-14034 SR lower dose at Week 6. Up to one retreatment of AR-14034 SR will be administered between Weeks 16 and 52 according to protocol-specified disease activity criteria. Sham procedures will be performed between Weeks 16 and 52 except when AR-14034 SR repeat treatment is administered.

    One IVT injection of aflibercept 2 mg at Baseline, Week 4, and Week 8, with one IVT insertion of AR-14034 SR higher dose at Week 6. Up to one retreatment of AR-14034 SR will be administered between Weeks 16 and 52 according to protocol-specified disease activity criteria. Sham procedures will be performed between Weeks 16 and 52 except when AR-14034 SR repeat treatment is administered.

    One IVT injection of aflibercept 2 mg at Baseline, Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, and Week 48. Sham procedures will be performed between Weeks 16 and 52.

    Outcomes

    Primary Outcome Measures

    Mean change from baseline in ETDRS BCVA at the average across two visits, Weeks 44 and 48 (Stage 2)
    Visual acuity will be measured after manifest refraction using Early Treatment of Diabetic Retinopathy Study (ETDRS) letter charts in a 4-meter lane under standard illumination. Best corrected visual acuity (BCVA) will be recorded as the number of letters read correctly. The difference between the average across Weeks 44 and 48, and the baseline visit will be reported. One eye (study eye) will contribute to the analysis.

    Secondary Outcome Measures

    Mean change from baseline in ETDRS BCVA by visit (Stage 2)
    Visual acuity will be measured after manifest refraction using ETDRS letter charts in a 4-meter lane under standard illumination. BCVA will be recorded as the number of letters read correctly. The difference between a given post-baseline visit and the baseline visit will be reported. One eye (study eye) will contribute to the analysis.
    Mean change from baseline in Central Subfield Thickness (CST) by visit (Stage 2)
    Central subfield thickness (CST) will be assessed using spectral domain optical coherence tomography (SD-OCT) imaging and measured in micrometers. The difference between a given post-baseline visit and the baseline visit will be reported. One eye (study eye) will contribute to the analysis.

    Full Information

    First Posted
    March 3, 2023
    Last Updated
    September 15, 2023
    Sponsor
    Aerie Pharmaceuticals
    Collaborators
    Alcon Research
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05769153
    Brief Title
    Study of AR-14034 in Participants With Neovascular Age-Related Macular Degeneration (nAMD)
    Acronym
    NOVA-1
    Official Title
    A Phase 1/2 Two-Stage Dose Escalation and Randomized Parallel-Group Study to Evaluate the Safety, Preliminary Treatment Effects, and Durability of AR-14034 Sustained Release Implant Compared to Intravitreal Anti-Vascular Endothelial Growth Factor Treatment in Participants With Neovascular Age-Related Macular Degeneration
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 2023 (Anticipated)
    Primary Completion Date
    January 2027 (Anticipated)
    Study Completion Date
    January 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Aerie Pharmaceuticals
    Collaborators
    Alcon Research

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The primary purpose of this study is to evaluate the safety and durability of single- and repeat administration of AR-14034 Sustained Release (SR) in subjects with neovascular age-related macular degeneration (nAMD).
    Detailed Description
    This study will be conducted in two stages. Stage 1 is a 48-week, dose-escalation, open-label evaluation of AR-14034 SR. Two cohorts will be enrolled, for an approximate total of 10 subjects. Subjects in both cohorts will attend visits through Week 48 for assessment of safety and preliminary treatment effects. Stage 2 is a 56-week (plus extension) double-masked, active comparator, randomized, parallel group evaluation of AR-14034 SR compared with aflibercept. Approximately 130 subjects will be enrolled and randomized 2:2:1 to AR-14034 SR lower dose, AR-14034 SR higher dose, or aflibercept dosed as labelled. Subjects will attend visits through Week 56 for assessment of safety and treatment effects. A 16-week open label extension phase will be conducted thereafter.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Neovascular Age-related Macular Degeneration (nAMD)
    Keywords
    nAMD, retina, eyes, ophthalmology

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Parallel Assignment
    Model Description
    Stage 1 will enroll 2 cohorts. Stage 2 will enroll 3 treatment arms.
    Masking
    ParticipantInvestigator
    Masking Description
    Stage 1 is open label. Stage 2 is double-masked.
    Allocation
    Randomized
    Enrollment
    140 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Cohort 1 (Stage 1)
    Arm Type
    Experimental
    Arm Description
    One intravitreal (IVT) injection of aflibercept 2 mg at Week -1 and one IVT insertion of AR-14034 SR lower dose at Baseline. Up to one retreatment with AR-14034 SR will be administered between Weeks 4 and 36 according to protocol-specified disease activity criteria.
    Arm Title
    Cohort 2 (Stage 1)
    Arm Type
    Experimental
    Arm Description
    One IVT injection of aflibercept 2 mg at Week -1 and one IVT insertion of AR-14034 SR higher dose at Baseline. Up to one retreatment with AR-14034 SR will be administered between Weeks 4 and 36 according to protocol-specified disease activity criteria.
    Arm Title
    AR-14034 SR lower dose (Stage 2)
    Arm Type
    Experimental
    Arm Description
    One IVT injection of aflibercept 2 mg at Baseline, Week 4, and Week 8, with one IVT insertion of AR-14034 SR lower dose at Week 6. Up to one retreatment of AR-14034 SR will be administered between Weeks 16 and 52 according to protocol-specified disease activity criteria. Sham procedures will be performed between Weeks 16 and 52 except when AR-14034 SR repeat treatment is administered.
    Arm Title
    AR-14034 SR higher dose (Stage 2)
    Arm Type
    Experimental
    Arm Description
    One IVT injection of aflibercept 2 mg at Baseline, Week 4, and Week 8, with one IVT insertion of AR-14034 SR higher dose at Week 6. Up to one retreatment of AR-14034 SR will be administered between Weeks 16 and 52 according to protocol-specified disease activity criteria. Sham procedures will be performed between Weeks 16 and 52 except when AR-14034 SR repeat treatment is administered.
    Arm Title
    Aflibercept (Stage 2)
    Arm Type
    Active Comparator
    Arm Description
    One IVT injection of aflibercept 2 mg at Baseline, Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, and Week 48. Sham procedures will be performed between Weeks 16 and 52.
    Intervention Type
    Drug
    Intervention Name(s)
    AR-14034 SR implant lower dose
    Intervention Description
    AR-14034 SR administered as an intravitreal implant
    Intervention Type
    Drug
    Intervention Name(s)
    Aflibercept Injection
    Intervention Description
    Aflibercept administered as a 2 milligram (mg) intravitreal injection
    Intervention Type
    Drug
    Intervention Name(s)
    Sham procedure
    Intervention Description
    Needleless syringe used to simulate an intravitreal injection
    Intervention Type
    Drug
    Intervention Name(s)
    AR-14034 SR implant higher dose
    Intervention Description
    AR-14034 SR administered as an intravitreal implant
    Primary Outcome Measure Information:
    Title
    Mean change from baseline in ETDRS BCVA at the average across two visits, Weeks 44 and 48 (Stage 2)
    Description
    Visual acuity will be measured after manifest refraction using Early Treatment of Diabetic Retinopathy Study (ETDRS) letter charts in a 4-meter lane under standard illumination. Best corrected visual acuity (BCVA) will be recorded as the number of letters read correctly. The difference between the average across Weeks 44 and 48, and the baseline visit will be reported. One eye (study eye) will contribute to the analysis.
    Time Frame
    Baseline, Week 44, Week 48
    Secondary Outcome Measure Information:
    Title
    Mean change from baseline in ETDRS BCVA by visit (Stage 2)
    Description
    Visual acuity will be measured after manifest refraction using ETDRS letter charts in a 4-meter lane under standard illumination. BCVA will be recorded as the number of letters read correctly. The difference between a given post-baseline visit and the baseline visit will be reported. One eye (study eye) will contribute to the analysis.
    Time Frame
    Baseline to Week 56
    Title
    Mean change from baseline in Central Subfield Thickness (CST) by visit (Stage 2)
    Description
    Central subfield thickness (CST) will be assessed using spectral domain optical coherence tomography (SD-OCT) imaging and measured in micrometers. The difference between a given post-baseline visit and the baseline visit will be reported. One eye (study eye) will contribute to the analysis.
    Time Frame
    Baseline to Week 56

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Key Inclusion Criteria [Stage 1 and Stage 2]: Presence of an active choroidal neovascularization (CNV) lesion secondary to age-related macular degeneration (AMD); Best corrected visual acuity (BCVA) between 80 and 35 letters (20/25 to 20/200 Snellen equivalent) in the study eye; BCVA greater than 34 letters (approximately 20/200 Snellen equivalent) in the non-study eye; Media clarity and pupillary dilation in the study eye sufficient for all planned study procedures; Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol; Other protocol-specified inclusion criteria may apply. [Stage 1]: Greater than or equal to 3 and less than or equal to 6 prior treatments of an ocular anti-VEGF medication within the 8 months prior to Screening in the study eye, with demonstrated anatomic response, as assessed by the Investigator. [Stage 2]: Treatment-naïve, or initial diagnosis of exudative neovascular age-related macular degeneration (nAMD) in the study eye within 9 months before Screening. Key Exclusion Criteria [Stage 1 and Stage 2]: History or current ocular disease in the study eye other than nAMD, that, might require medical or surgical intervention during the study; Structural damage to the macula that is likely to preclude improvement in visual acuity in the study eye after resolution of the nAMD; Any active intraocular or periocular infection or active intraocular inflammation; Treatment with ocular anti-VEGF product within 28-days before Week -1 [Stage 1] or Baseline [Stage 2]; Uncontrolled glaucoma in the study eye; Uncontrolled blood pressure; Females of child-bearing potential who are pregnant, intending to become pregnant, nursing, or who are not willing to use an acceptable form of contraception for the duration of the study; Other protocol-specified exclusion criteria may apply.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Alcon Call Center
    Phone
    1-888-451-3937
    Email
    alcon.medinfo@alcon.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Director of Clinical Development, Alcon
    Organizational Affiliation
    Aerie Pharmaceuticals
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Study of AR-14034 in Participants With Neovascular Age-Related Macular Degeneration (nAMD)

    We'll reach out to this number within 24 hrs