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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Neovascular Age-related Macular Degeneration (nAMD)
• Intervention / Treatment: Drug: AR-14034 SR implant lower dose; Drug: Aflibercept Injection; Drug: AR-14034 SR implant higher dose; Drug: Sham procedure; Drug: AR-14034 SR implant

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 will receive AR-14034 SR in one of two dose levels and 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 one injection, AR-14034 SR two injections, 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.

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Dothan, Alabama, United States, 36301
      • Trinity Research Group
  • Arizona
    • Gilbert, Arizona, United States, 85297
      • Associated Retina Consultants - Gilbert
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants - Phoenix
    • Tucson, Arizona, United States, 85704
      • Retina Associates of SW PC
  • California
    • Encino, California, United States, 91436
      • The Retina Partners
    • Laguna Hills, California, United States, 92653
      • Retina Associates of Orange County
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates Medical Group
    • Newport Beach, California, United States, 92663
      • Eye Research Foundation
    • Pasadena, California, United States, 99107
      • Azul Vision Pasadena
  • Colorado
    • Colorado Springs, Colorado, United States, 80809
      • Retina Consultants of Southern Colorado
  • Connecticut
    • Waterford, Connecticut, United States, 06385
      • Retina Group of New England | Waterford
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Florida Retina Institute
    • Mt. Dora, Florida, United States, 32757
      • Mid Florida Eye Center
    • Orlando, Florida, United States, 32806
      • Florida Retina Institute
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
    • Pinellas Park, Florida, United States, 33782
      • Eye Associates of Pinellas
    • Winter Haven, Florida, United States, 33880
      • Center for Retina and Macular Disease
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
    • Sandy Springs, Georgia, United States, 30328
      • Thomas Eye Group Main Office
  • Illinois
    • Oak Forest, Illinois, United States, 60452
      • University Retina and Macula Associates, PC
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Twin Cities Eye Consultants
  • Mississippi
    • Madison, Mississippi, United States, 39110
      • Mississippi Retina Associates
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Vision Research Center Eye Associates of New Mexico
  • New York
    • Forest Hills, New York, United States, 11375
      • NYC Retina - Queens
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Verum Research, LLC
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • Erie Retina Research
    • Philadelphia, Pennsylvania, United States, 19107
      • MidAtlantic Retina Research
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Retina Consultants of Carolina
    • Mt. Pleasant, South Carolina, United States, 29464
      • Carolina Eyecare Physicians LLC
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Arlington, Texas, United States, 76012
      • Texas Retina Associates - Arlington
    • Austin, Texas, United States, 78705
      • Austin Retina Associates
    • Austin, Texas, United States, 78705
      • Austin Research Center for Retina
    • Austin, Texas, United States, 78750
      • Austin Clinical Research, LLC
    • Burleson, Texas, United States, 76028
      • Star Vision Research
    • Dallas, Texas, United States, 75231
      • Texas Retina Associates
    • Houston, Texas, United States, 77027
      • Berkeley Eye Center
    • San Antonio, Texas, United States, 78251
      • Retina Consultants of Texas - San Antonio
    • San Marcos, Texas, United States, 78666
      • Austin Retina Associates (San Marcos)
  • Utah
    • St. George, Utah, United States, 84790
      • Retina Research Center of Southern Utah
  • Washington
    • Burlington, Washington, United States, 98233
      • Pacific Northwest Retina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 20 letters (approximately 20/400 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 diagnosis of exudative neovascular age-related macular degeneration (nAMD) in the study eye.

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 in the study eye within 28 days before Week 1 [Stage 1] or within 56 days before Screening [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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (Stage 1); 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.	Drug: AR-14034 SR implant lower dose; AR-14034 SR administered as an intravitreal implant; Drug: Aflibercept Injection; Aflibercept administered as a 2 milligram (mg) intravitreal injection
Experimental: Cohort 2 (Stage 1); 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.	Drug: Aflibercept Injection; Aflibercept administered as a 2 milligram (mg) intravitreal injection; Drug: AR-14034 SR implant higher dose; AR-14034 SR administered as an intravitreal implant
Experimental: AR-14034 SR one injection (Stage 2); One IVT injection of aflibercept 2 mg at Baseline, Week 4, and Week 8, with one IVT insertion of AR-14034 SR at Week 2. Sham procedures will be performed between Baseline and Week 52 when other arms are receiving scheduled treatment injections.	Drug: Aflibercept Injection; Aflibercept administered as a 2 milligram (mg) intravitreal injection; Drug: Sham procedure; Needleless syringe used to simulate an intravitreal injection; Drug: AR-14034 SR implant; AR-14034 SR administered as an intravitreal implant
Experimental: AR-14034 SR two injections (Stage 2); One IVT injection of aflibercept 2 mg at Baseline, Week 4, and Week 8, with IVT insertions of AR-14034 SR at Week 2 and Week 6. Sham procedures will be performed between Baseline and Week 52 when other arms are receiving scheduled treatment injections.	Drug: Aflibercept Injection; Aflibercept administered as a 2 milligram (mg) intravitreal injection; Drug: Sham procedure; Needleless syringe used to simulate an intravitreal injection; Drug: AR-14034 SR implant; AR-14034 SR administered as an intravitreal implant
Active Comparator: Aflibercept (Stage 2); 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 Baseline and Week 52 when other arms are receiving scheduled treatment injections.	Drug: Aflibercept Injection; Aflibercept administered as a 2 milligram (mg) intravitreal injection; Drug: Sham procedure; Needleless syringe used to simulate an intravitreal injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 44, Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to Week 56
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.	Baseline to Week 56

Collaborators and Investigators

• Sponsor: Alcon Research
• Collaborators: Alcon Research
• Investigators: Study Director: Director of Clinical Development, Alcon, Alcon Research, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2023
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: March 3, 2023
• First Submitted That Met QC Criteria: March 3, 2023
• First Posted (Actual): March 15, 2023

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: eyes; retina; ophthalmology; nAMD
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Wet Macular Degeneration; Antineoplastic Agents; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; aflibercept
• Other Study ID Numbers: RTE888-E001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No