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

Alcon

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Neovascular Age-related Macular Degeneration (nAMD)

Treatments: Drug: AR-14034 SR implant lower dose; Drug: AR-14034 SR implant higher dose; Drug: Sham procedure; Drug: Aflibercept Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT05769153

RTE888-E001

Details and patient eligibility

About

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).

Full 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.

Enrollment: 140 estimated patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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140 participants in 5 patient groups

Cohort 1 (Stage 1)

Experimental group

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.

Treatment:

Drug: Aflibercept Injection

Drug: AR-14034 SR implant lower dose

Cohort 2 (Stage 1)

Experimental group

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.

Treatment:

Drug: Aflibercept Injection

Drug: AR-14034 SR implant higher dose

AR-14034 SR lower dose (Stage 2)

Experimental group

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.

Treatment:

Drug: Aflibercept Injection

Drug: Sham procedure

Drug: AR-14034 SR implant lower dose

AR-14034 SR higher dose (Stage 2)

Experimental group

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.

Treatment:

Drug: Aflibercept Injection

Drug: AR-14034 SR implant higher dose

Drug: Sham procedure

Aflibercept (Stage 2)

Active Comparator group

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.

Treatment:

Drug: Aflibercept Injection

Drug: Sham procedure