Efficacy and Safety of RTH258 Versus Aflibercept - Study 1 (HAWK)

Alcon

Status and phase: Completed; Phase 3

Conditions: Choroidal Neovascularization; Neovascular Age-Related Macular Degeneration

Treatments: Drug: Aflibercept ophthalmic solution; Drug: Brolucizumab ophthalmic solution

Study type: Interventional

Funder types: Industry

Identifiers

NCT02307682

RTH258-C001

CRTH258A2301 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to compare brolucizumab (RTH258) ophthalmic solution for intravitreal (IVT) injection at two dosage levels (3 mg and 6 mg) to aflibercept ophthalmic solution for IVT injection (2 mg) in subjects with untreated active choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) in the study eye.

Full description

Subjects were randomized to brolucizumab 3 mg, brolucizumab 6 mg,and aflibercept 2 mg in a 1:1:1 ratio. Subjects in all treatment arms received 3 monthly loading doses (Day 0, Week 4 and Week 8), followed by a maintenance regimen, until the end of the study (Week 96/Exit). All subjects attended pre-specified visits every 4 weeks.

Subjects in the brolucizumab 3 mg and brolucizumab 6 mg arms followed a q12w/q8w maintenance regimen. Within the q12w/q8w regimen, the initial treatment after the loading phase was q12w (1 injection every 12 weeks). If disease activity was identified by the masked investigator at any of the disease activity assessments, dosing was adjusted to q8w (1 injection every 8 weeks) ("q12w/q8w regimen"). Once subjects were adjusted to the q8w interval, they stayed on that interval until the end of the study.

Subjects in the aflibercept 2 mg arm followed a q8w maintenance regimen until the end of the study.

Results reported up to Week 48 are based on the database locked for the primary analysis at Week 48. Results reported after Week 48 are based on the database locked at the end of study (final analysis).

Enrollment: 1,775 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Provide written informed consent
• Active choroidal neovascularization (CNV) lesions secondary to age-related macular degeneration (AMD) that affected the central subfield in the study eye at Screening;
• Total area of CNV comprising >50% of the total lesion area in the study eye at Screening;
• Intraretinal and/or subretinal fluid affecting the central subfield of the study eye at Screening;
• Best Corrected Visual Acuity (BCVA) between 78 and 23 letters, inclusive, in the study eye at Screening and Baseline using Early Treatment Diabetic Retinopathy Study (ETDRS) testing.

Key Exclusion Criteria:

• Any active intraocular or periocular infection or active intraocular inflammation in either eye at Baseline;
• Central subfield of the study eye affected by fibrosis or geographic atrophy or total area of fibrosis >50% of the total lesion in the study eye at Screening;
• Subretinal blood affecting the foveal center point and/or >50% of the lesion of the study eye at Screening;
• Any approved or investigational treatment for neovascular age-related macular degeneration (nAMD) in the study eye at any time;
• Retinal pigment epithelial rip/tear in the study eye at Screening or Baseline or current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to Baseline;
• Pregnant or nursing women; women of child-bearing potential;
• Stroke or myocardial infarction in the 90-day period prior to Baseline.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

1,775 participants in 3 patient groups

Brolucizumab 3 mg

Experimental group

Description:

Single intravitreal (IVT) injection of brolucizumab ophthalmic solution administered as a 3 mg/50 microliter (μL) dose at Day 0, Week 4, and Week 8, followed by 1 injection every 8 weeks/1 injection every 12 weeks (q8w/q12w) maintenance regimen until study exit

Treatment:

Drug: Brolucizumab ophthalmic solution

Brolucizumab 6 mg

Experimental group

Description:

Single IVT injection of brolucizumab ophthalmic solution administered as a 6 mg/50 μL dose at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit

Treatment:

Drug: Brolucizumab ophthalmic solution

Aflibercept 2 mg

Active Comparator group

Description:

Single IVT injection of aflibercept ophthalmic solution administered as a 2 mg/50 μL dose at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit

Treatment:

Drug: Aflibercept ophthalmic solution