Clinical Studies:
HARBOR
Citation: Ho AC, Busbee BG, Regillo CD, et al. Twenty-four-month efficacy and safety of 0.5mg or 2.0 ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology 2014; 121: 2181-2192
Key Points
- The HARBOR trial was a randomized, treatment-controlled trial that compared ranibizumab 0.5mg monthly, 0.5.mg x 3 then monthly PRN, 2mg monthly, and 2mg x 3 then monthly PRN for choroidal neovascularization (CNV) from age-related macular degeneration (AMD)
- There was no significant difference at 24 months in visual outcomes for patients treated with ranibizumab 0.5mg monthly, 0.5.mg x 3 then monthly PRN, 2mg monthly, or 2mg x 3 then monthly PRN (PRN treatment criteria was vision decrease or activity on OCT imaging), with a mean treatment interval of 9.9 weeks (0.5mg PRN) or 12.5 weeks (2mg PRN) in the PRN groups.
- Adverse ocular and non-ocular events, including Antiplatelet Trialists’ Collaboration criteria (APTC), were similar across all groups
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Objective
To study the efficacy of ranibizumab 0.5mg vs. 2 mg monthly vs. PRN for age-related macular degeneration (AMD)
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STUDY DESIGN
Phase 3, multicenter, randomized, double-masked, treatment-controlled trial
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Duration
24 months
STUDY SUBJECTS
- treatment-naïve AMD with subfoveal lesion on FA (all subtypes -- predominantly classic, minimally classic, and occult) ▪ For occult lesions, documented activity including: >10% increase in lesion size, ≥ 1 line vision loss, or hemorrhage
Major Inclusion criteria:
- history of VR surgery, any prior treatment for AMD
Major exclusion criteria:
RANDOMIZATION SCHEME AND INTERVENTIONS
Randomized (stratified by vision (VA ≤ 20/80; VA > 20/80); lesion subtype; study center) 1:1:1:1 to
(a) ranibizumab 0.5mg monthly
(b) ranibizumab 2mg monthly
(c) ranibizumab 0.5mg monthly x 3 then monthly PRN
(d) ranibizumab 2mg monthly x 3 then monthly PRN
Retreatment criteria for PRN group: monthly evaluation and treatment if ≥ 5 letter decrease in vision or disease activity on OCT (IRF, SRF, sub-RPE fluid)
RESULTS (24 months)
Study population:
- 1097 subjects
- Study completion 86%; similar across all groups
Visual acuity end-points
- Loss of < 15 letters: 90-94%, similar across all groups
- Gain of > 15 letter: 33-37%, similar across all groups
- Mean VA change similar in all groups: +9.1 letters (0.5mg monthly), +8.0 (2mg monthly), +7.9 (0.5mg PRN), +7.6 letters (2mg PRN)
# of injections
- At 12 mth: 11.3 (0.5mg monthly), 11.2 (2mg monthly), 7.7 (0.5mg PRN), 6.9 (2mg PRN)
- At 24 mth: 21.4 (0.5mg monthly), 21.6 (2mg monthly), 13.3 (0.5mg PRN), 11.2 (2mg PRN)
- Average treatment interval after the loading doses: 9.9 weeks (0.5mg PRN) and 12.5 weeks (2mg PRN)
Anatomic end-points on OCT
- Mean change in central foveal thickness (CFT) were similar in all groups: -183µm (0.5mg monthly), -172µm (2mg monthly), -172 µm (0.5mg PRN), -181µm (2mg PRN)
Angiographic end-points
- Mean change in total lesion area was similar in all groups: -1.6 disc areas (DA) (0.5mg monthly), -2.1 DA (2mg monthly), -1.1 DA (0.5mg PRN), -1.4 (2mg PRN)
Adverse events
- APTC events were similar in all four groups: 6.6% (0.5mg monthly), 5.8% (2mg monthly), 4.7% (0.5mg PRN), 5.9% (2mg PRN)
CONCLUSIONS
- Similar visual and anatomical outcomes in all 4 groups