Phase 3
Completed N=1,082
Efficacy and Safety of RTH258 Versus Aflibercept - Study 1
Neovascular Age-Related Macular Degeneration · Choroidal Neovascularization
Source: ClinicalTrials.gov NCT02307682 ↗
Enrolled (actual)
1,082
Serious AEs
28.1%
Results posted
Oct 2019
Primary outcomePrimary: Change From Baseline in Best Corrected Visual Acuity (BCVA) (Letters Read) at Week 48 - Study Eye — 5.9; 6.4; 7.0 letters — p=0.0003
◆ Published Evidence
Highly cited
943citations · ~157 / year
HAWK and HARRIER: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration.
Summary
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.
Linked Publications (5)
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HAWK and HARRIER: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration.
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Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER.
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Bacillary Layer Detachment in Neovascular Age-Related Macular Degeneration from a Phase III Clinical Trial.
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Efficacy Outcomes of Brolucizumab Versus Aflibercept in Neovascular Age-Related Macular Degeneration Patients with Early Residual Fluid.
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Effect of Brolucizumab and Aflibercept on the Maximum Thickness of Pigment Epithelial Detachments and Sub-Retinal Pigment Epithelium Fluid in HAWK and HARRIER.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Best Corrected Visual Acuity (BCVA) (Letters Read) at Week 48 - Study Eye |
5.9; 6.4; 7.0 | 0.0003 sig |
| SECONDARY Average Change From Baseline in BCVA (Letters Read) Over the Period Week 36 Through Week 48 - Study Eye |
6.0; 6.5; 6.9 | 0.0001 sig |
| SECONDARY Proportion of Subjects With Positive q12 (Every 12 Weeks) Treatment Status at Week 48 |
0.4939; 0.5563 | — |
| SECONDARY Proportion of Subjects With Positive q12 Treatment Status at Week 48 Within the Subjects With no q8 (Every 8 Weeks) Treatment Need During the First q12 Cycle (Week 16, Week 20) |
0.8085; 0.8539 | — |
| SECONDARY Proportion of Subjects With Positive q12 Treatment Status up to Week 96 |
0.3973; 0.4537 | — |
| SECONDARY Proportion of Subjects With Positive q12 Treatment Status at Week 96 Within the Subjects With no q8 Treatment Need During the Initial q12 Cycle (Week 16, Week 20) |
0.6504; 0.6963 | — |
| SECONDARY Change From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye |
3.7; 3.8; 4.2; 5.7; 5.5; 6.1 | — |
| SECONDARY Average Change From Baseline in BCVA (Letters Read) Over the Period Week 4 to Week 48/96 - Study Eye |
5.7; 6.2; 6.5; 5.8; 6.0; 6.4 | — |
| SECONDARY Average Change From Baseline in BCVA (Letters Read) Over the Period Week 12 to Week 48/96 - Study Eye |
5.9; 6.5; 6.7; 5.9; 6.1; 6.5 | — |
| SECONDARY Average Change From Baseline in BCVA (Letters Read) Over the Period Week 84 to Week 96 - Study Eye |
5.7; 5.7; 5.7 | — |
| SECONDARY Percentage of Subjects With >=15 Letter Gain From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye |
9.2; 10.8; 9.7; 15.9; 19.2; 15.6 | — |
| SECONDARY Percentage of Subjects With >=10 Letter Gain From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye |
19.3; 24.4; 19.2; 30.7; 32.5; 32.2 | — |
| SECONDARY Percentage of Subjects With >=5 Letter Gain From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye |
40.2; 43.3; 43.1; 54.2; 53.1; 56.1 | — |
| SECONDARY Percentage of Subjects With >=15 Letter Loss From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye |
1.7; 3.1; 1.4; 1.7; 2.8; 2.2 | — |
| SECONDARY Percentage of Subjects With >=10 Letter Loss From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye |
3.6; 4.4; 4.2; 3.4; 3.9; 3.9 | — |
| SECONDARY Percentage of Subjects With >=5 Letter Loss From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye |
9.8; 10.3; 7.8; 7.5; 10.3; 7.5 | — |
| SECONDARY Percentage of Subjects With BCVA of 73 Letters Read or More at Each Visit - Study Eye |
24.9; 21.7; 19.2; 34.6; 33.3; 33.9 | — |
| SECONDARY Change From Baseline in Central Subfield Thickness (CSFTtot) at Each Post-baseline Visit - Study Eye |
-142.2; -150.9; -137.8; -163.7; -169.1; -154.3 | 0.0159 sig |
| SECONDARY Average Change From Baseline in CSFTtot Over the Period Week 36 Through Week 48 - Study Eye |
-166.9; -170.1; -151.8 | 0.0183 sig |
| SECONDARY Average Change From Baseline in CSFTtot Over the Period Week 84 Through Week 96 - Study Eye |
-177.7; -173.0; -158.4 | — |
| SECONDARY Average Change From Baseline in CSFTtot Over the Period Week 4 Through Week 48/96 - Study Eye |
-161.0; -165.2; -149.3; -167.5; -167.8; -152.4 | — |
| SECONDARY Change From Baseline in Choroidal Neovascularization (CNV) Lesion Size at Week 12, Week 48, and Week 96 - Study Eye |
-3.3; -3.8; -3.2; -3.9; -4.0; -3.5 | — |
| SECONDARY Change From Baseline in Central Subfield Neurosensory Retinal Thickness (CSFTns) at Each Post-baseline Visit - Study Eye |
-56.3; -62.1; -61.0; -63.7; -66.3; -63.2 | — |
| SECONDARY Percentage of Subjects With Presence of Subretinal Fluid at Each Post-baseline Visit - Study Eye |
33.2; 28.9; 42.8; 19.0; 12.8; 27.5 | — |
| SECONDARY Percentage of Subjects With Presence of Intraretinal Fluid at Each Post-baseline Visit - Study Eye |
20.4; 23.9; 22.2; 17.9; 20.8; 22.5 | — |
| SECONDARY Percentage of Subjects With Presence of Sub-retinal Pigment Epithelium (RPE) Fluid at Each Post-baseline Visit - Study Eye |
25.4; 24.2; 29.2; 16.5; 17.5; 21.4 | — |
| SECONDARY Percentage of Subjects With Presence of Subretinal and/or Intraretinal Fluid at Each Post-baseline Visit - Study Eye |
47.8; 47.2; 54.7; 32.7; 30.3; 42.5 | 0.0030 sig |
| SECONDARY Number of Subjects With Subretinal Fluid (SRF) and/or Intraretinal Fluid (IRF) Present Between Week 36 to Week 48, Reported by Number of Visits |
154; 171; 153; 67; 73; 48 | 0.0574 |
| SECONDARY Percentage of Subjects With Disease Activity Present (q8 Treatment Need = "Yes") at Week 16 - Study Eye |
28.0; 24.0; 34.6 | 0.0331 sig |
| SECONDARY Change From Baseline in Visual Function Questionnaire (VFQ-25) Composite Score at Week 24, Week 48, Week 72, and Week 96 |
4.4; 4.0; 3.5; 4.3; 4.1; 4.5 | — |
| SECONDARY Percentage of Subjects With Induced or Boosted Anti-drug Antibody (ADA) Status at Week 48 (Brolucizumab Only) |
25.6; 20.4; 65.8 | — |
| SECONDARY Percentage of Subjects With Intraretinal Hemorrhage (Central Subfield) Present at the Visit While Absent at Baseline at Each Treatment - Study Eye |
0.0; 0.3; 0.9; 0.0; 0.0; 0.0 | — |
| SECONDARY Percentage of Subjects With Subretinal Hemorrhage (Central Subfield) Present at the Visit While Absent at Baseline at Each Treatment - Study Eye |
1.6; 2.4; 0.7; 1.8; 0.4; 2.6 | — |
Eligibility 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.
Data sourced from ClinicalTrials.gov (NCT02307682) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.