11) in Group I and 3.5 injections (range 1-12) in Group II. In Group II, which is the recommended posology (see section 4.2), 50.9% of patients required 1 or 2 injections, 34.5% required 3 to 5 injections and 14.7% required 6 to 12 injections over the 12-month study period. 62.9% of Group II patients did not require injections in the second 6 months of the study.
The key outcomes from RADIANCE are summarised in Table 7 and Figure 5.
Table 7 Outcomes at Month 3 and 12 (RADIANCE)
Group I
Ranibizumab
0.5 mg
“vision stability”
(n=105)
Group II
Ranibizumab
0.5 mg
“disease activity”
(n=116)
Group III
vPDTb
(n=55)
Month 3
Mean average BCVA change from Month 1 to Month 3 compared to baselinea (letters)
+10.5
+10.6
+2.2
Proportion of patients who gained:
≥10 letters, or reached ≥84 letters in BCVA
≥15 letters, or reached ≥84 letters in BCVA
61.9%
38.1%
65.5%
43.1%
27.3%
14.5%
Month 12
Number of injections up to Month 12:
Mean
Median
4.6
4
3.5
2.0
N/A
N/A
Mean average BCVA change from Month 1 to Month 12 compared to baseline (letters)
+12.8
+12.5
N/A
Proportion of patients who gained:
≥10 letters, or reached ≥84 letters in BCVA
≥15 letters, or reached ≥84 letters in BCVA
69.5%
53.3%
69.0%
51.7%
N/A
N/A
a p<0.00001 comparison with vPDT control
b Comparative control up to Month 3. Patients randomised to vPDT were allowed to receive ranibizumab treatment as of Month 3 (in Group III, 38 patients received ranibizumab as of Month 3)
Figure 5 Mean change from baseline BCVA over time to Month 12 (RADIANCE)
The improvement of vision was accompanied by a reduction in central retinal thickness.
Patient-reported benefits were observed with ranibizumab treatment arms over vPDT (p-value <0.05) in terms of improvement in the composite score and several subscales (general vision, near activities, mental health and dependency) of the NEI VFQ-25.
Paediatric population
The safety and efficacy of ranibizumab have not yet been studied in paediatric patients.
The European Medicines Agency has waived the obligation to submit the results of studies with Lucentis in all subsets of the paediatric population in neovascular AMD, visual impairment due to DME, visual impairment due to macular oedema secondary to RVO and visual impairment due to CNV secondary to PM (see section 4.2 for information on paediatric use).
5.2 Pharmacokinetic properties
Following monthly intravitreal administration of Lucentis to patients with neovascular AMD, serum concentrations of ranibizumab were generally low, with maximum levels (Cmax) generally below the ranibizumab concentration necessary to inhibit the biological activity of VEGF by 50% (11-27 ng/ml, as assessed in an in vitro cellular proliferation assay). Cmax was dose proportional over the dose range of 0.05 to 1.0 mg/eye. Serum concentrations in a limited number of DME patients indicate that a slightly higher systemic exposure cannot be excluded comp
