Clinical Studies:
CHROMA
Citation: Holz FG, Sadda SR, Busbee B, et al. Efficacy and Safety of Lampalizumab for Geographic Atrophy Due to Age-Related Macular Degeneration: Chroma and Spectri Phase 3 Randomized Clinical Trials. JAMA Ophthalmol. 2018;136(6):666-677.
Key Points
- CHROMA was an international, randomized, double-masked, sham-controlled phase 3 trial that evaluated the effect of intravitreal lampalizumab 10 mg administered every 4 or 6 weeks vs sham procedure on the enlargement of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
- There was no reduction in GA lesion growth with lampalizumab compared to sham at either dosing interval, including in patients with complement factor I (CFI) risk alleles.
- Lampalizumab was well-tolerated, with a low rate of ocular serious adverse events and no new safety signals, but did not demonstrate clinical efficacy in slowing GA progression.
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Objective
To evaluate the safety and efficacy of lampalizumab, a selective complement factor D inhibitor, in slowing the progression of GA.
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Study Design
Phase 3, randomized, double-masked, sham-controlled, multicenter trial. Conducted in parallel with the identically designed SPECTRI trial.
Subjects
- Inclusion criteria:
- Age ≥50 years
- GA lesion area 2.54–17.78 mm²
- Bilateral GA with no evidence of active or prior choroidal neovascularization (CNV)
- Diffuse or banded fundus autofluorescence pattern
- ETDRS BCVA ≥49 letters (= 20/100 or better)
- Exclusion criteria:
- CNV in either eye (current or prior), prior anti-VEGF therapy
- GA due to causes other than AMD
Randomization Scheme/Study Interventions
- Randomized 2:1:2:1 to:
- Intravitreal Lampalizumab 10 mg every 4 weeks
- Sham every 4 weeks
- Intravitreal Lampalizumab 10 mg every 6 weeks
- Sham every 6 weeks
Primary Endpoint
- Mean change in GA lesion area from baseline to week 48 based on fundus autofluorescence images
Results
- 906 participants; 92.1% study completion
- No significant difference in GA lesion area between lampalizumab and sham in either dosing group (−0.02 mm² for monthly, +0.05 mm² for q6w)
- No benefit in complement factor I (CFI) biomarker subgroups
- Mean GA lesion growth = ~2 mm²/year
- Mean BCVA decline of 4-5 ETDRS letters over 48 weeks in all groups (−4.9 sham, −4.1 q4w, −4.9 q6w)
Safety
- Ocular serious adverse events were higher in lampalizumab arms (~6% vs ~3% with sham), mostly due to expected intravitreal injection risks (i.e. IOP spikes and endophthalmitis)
- Endophthalmitis rate = 0.04%
- No new systemic safety concerns
Conclusions
- Lampalizumab did not demonstrate efficacy in reducing GA lesion progression over 48 weeks of treatment.
- These results highlight the progressive nature of GA and the visual burden it causes patients.