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

Sponsor

Aerie Pharmaceuticals (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05769153

Collaborator

Alcon Research (Industry)

140

Enrollment

Arms

Anticipated Duration (Months)

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Neovascular Age-related Macular Degeneration (nAMD)	Drug: AR-14034 SR implant lower dose Drug: Aflibercept Injection Drug: Sham procedure Drug: AR-14034 SR implant higher dose	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

140 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Stage 1 will enroll 2 cohorts. Stage 2 will enroll 3 treatment arms.Stage 1 will enroll 2 cohorts. Stage 2 will enroll 3 treatment arms.

Masking:

Double (Participant, Investigator)

Masking Description:

Stage 1 is open label. Stage 2 is double-masked.

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Nov 1, 2026

Anticipated Study Completion Date :

Nov 1, 2026

Arms and Interventions

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 16 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 16 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 lower dose (Stage 2) 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.	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 Drug: Sham procedure Needleless syringe used to simulate an intravitreal injection
Experimental: AR-14034 SR higher dose (Stage 2) 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.	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 higher dose 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 Weeks 16 and 52.	Drug: Aflibercept Injection Aflibercept administered as a 2 milligram (mg) intravitreal injection Drug: Sham procedure Needleless syringe used to simulate an intravitreal injection

Outcome Measures

Primary Outcome Measures

Mean change from baseline in ETDRS BCVA averaged over Weeks 44-48 (Stage 2) [Baseline, Weeks 44-48]
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 of Week 44-48 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) [Baseline to Week 56]
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) [Baseline to Week 56]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts 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.