Efficacy and Safety of Ranibizumab Biosimilar QL1205 in Neovascular Age-related Macular Degeneration: A Phase 3 Randomized Trial
EudraCT 2018-004486-13 | Not reported | Hamouz J et al. (2024)
Hamouz, J., Nowosielska, A., Święch-Zubilewicz, A., Abengoechea, S., Baumane, K., Vajas, A., Siewierska, M., Veselovsky, M., Veith, M., Kerényi, Á., Mange, S., Baidya, K., Laganovska, G., Jürgens, I., Papp, A., Gosai, J., Štefanickova, J., Han, M., Fryczkowski, P., Zalewski, D., Wang, J., Wei, W. Efficacy and Safety of Ranibizumab Biosimilar QL1205 in Neovascular Age-related Macular Degeneration: A Phase 3 Randomized Trial. Ophthalmology Retina, 2024; -:1-10.
Locations
97 centers across Asia and Europe
Study Period
June 2019 – June 2021
Study Design
Phase 3, randomized, double-blind, parallel-group trial
Study Population
Experimental Group
Control Group
Follow-up Time: 52 weeks
Outcomes
Durability
Not reported
Vision
Best-Corrected Visual Acuity (BCVA)
Mean BCVA change at Week 8 (primary outcome):
• QL1205 = +6.3 ± 9.13 letters
• RBZ= +7.3 ± 8.82 letters
• Difference = -1.0 letters (95% CI: -2.46 to 0.36, p = 0.1434).
Mean BCVA change at Week 24:
• QL1205 = 9.2±10.44 letters
• RBZ = 9.6±9.81 letters
Mean BCVA change at Week 48:
• QL1205 = 10.6±11.89 letters
• RBZ = 11.2±11.80 letters
Mean BCVA change at Week 52:
• QL1205 = +10.6 ± 11.89 letters
• RBZ = +11.2 ± 11.80 letters
• Difference = -0.6 letters (95% CI: -2.46 to 1.26, p = 0.1459).
Vision Maintaining
The proportions of patients who lost 15 letters or less compared to baseline were similar between QL1205 and RBZ:
• Week 8 (98.6% vs 99.3%; difference, 0.71)
• Week 24 (97.8% vs 99.6%; difference, -1.82)
• Week 52 (97% vs 97.7%; difference, -0.66)
The proportions of patients gained 15 letters or more compared to baseline were similar between QL1205 and RBZ:
• Week 8 (12.7% vs 14.3%; difference, -1.61)
• Week 24 (26.9% vs 25.3%; difference, 1.63)
• Week 52 (37.2% vs 34.4%; difference, 2.81)
Other
N/A
Immunognicity
Treatment-induced ADA positivity at Week 8:
• QL1205 = 2.4%
• RBZ = 2.1%.
• No neutralizing antibodies detected.
Pharmokinetics
Mean plasma concentration at Week 20:
• QL1205 = 1435.0 pg/mL
• RBZ = 1741.3 pg/mL.
Anatomic
Central Foveal Thickness (CFT)
Mean CFT reduction at Week 52:
• QL1205 = -138.0 ± 120.2 µm
• RBZ = -149.6 ± 118.5 µm
• Difference = +11.6 µm (p = 0.8441).
Choroidal neovascularization (CNV)
Both the QL1205 group and the RBZ group showed decrease from baseline level in total size of CNV leakage area:
• At week 24(1.22±4.324 mm2 vs. 1.14±4.308 mm2, p=0.8703)
• At week 52 (1.40±5.079 mm2 vs. 1.84±4.423 mm2, p =0.2856).
Mean total size of CNV decreased from baseline in both groups with a mean change in lesion area for the QL1205 group and the RBZ group:
• 0.2±2.36 mm2 and 0.3±2.27 mm2 at week 24 (P=0.6508)
• 0.0±2.94 mm2 and 0.3±2.70 mm2 at week 52 (P=0.1900)
Others
• The proportions of patients with no intra- or sub-retinal fluid increased in both groups without significant difference throughout the study.
• The proportions of patients with retinal pigment epithelium detachments in the QL1205 group and the RBZ group both decreased from baseline to week 24 (7.9% vs. 9.8%) and week 52 (5.7% vs. 6.7%), respectively.
Safety
TEAEs
At least one TEAEs
• QL1205: 73.1%
• RBZ: 71.0%
At least one severe TEAE:
• QL1205: 7.4%
• RBZ: 5.9%
At least one serious TEAE:
• QL1205: 9.7%
• RBZ: 6.5%
At least one TEAE leading to discontinuation:
• QL1205: 1.6%
• RBZ: 2.6%
At least one TEAE leading to death:
• QL1205: 1.6%
• RBZ: 1.0%
Ocular TEAEs
Neovascular age-related macular degeneration:
• QL1205: 4.5%
• RBZ: 3.3%
Visual acuity reduced:
• QL1205: 3.2%
• RBZ: 3.9%
Conjunctival hemorrhage:
• QL1205: 3.9%
• RBZ: 2.6%
Intraocular pressure increased:
• QL1205: 3.9%
• RBZ: 2.6%
Endophthalmitis:
• QL1205: 0.3%
• RBZ: 0.3%
Non-Ocular TEAEs
Hypertension:
• QL1205: 5.8%
• RBZ: 7.5%
Back pain:
• QL1205: 3.9%
• RBZ: 3.6%
Urinary tract infection:
• QL1205: 3.9%
• RBZ: 2.3%
Headache:
• QL1205: 3.6%
• RBZ: 2.6%
Nasopharyngitis:
• QL1205: 3.2%
• RBZ: 3.3%
Upper respiratory tract infection:
• QL1205: 3.2%
• RBZ: 2.3%
Blood pressure increased:
• QL1205: 3.2%
• RBZ: 2.3%
Blood glucose increased:
• QL1205: 3.2%
• RBZ: 2.0%
Toothache:
• QL1205: 1.9%
• RBZ: 3.3%
Conclusion
QL1205 demonstrated equivalent efficacy, safety, pharmacokinetics, and immunogenicity compared to reference ranibizumab, supporting its use as a biosimilar for nAMD treatment.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: “Randomization was performed using an interactive web response system…An independent biostatistician created the randomization scheme, which remained unavailable to all other masked individuals until study completion.” “There was no significant difference in baseline characteristics between the two groups…”
Missing Outcome Data
Low risk
Note: The evidence that the result was not biased by missing outcome data: both the ITT set, and the per-protocol set (PPS) were applied for the primary outcome analysis.
Selection of the Reported Results
Low risk Note: Registration with the protocol.
Deviations from Intended Observations
Low risk Note: “Patients and investigators were both masked to the treatment assignment…” and ITT principle was applied in the data analysis.
Measurement of the Outcome
Some concerns Note: This is a double blinded study. However, this is a multiple-site study. There is no information on if the primary outcome assessment is consistent across all sites. However, assessment of the outcome could not have been influenced by knowledge of intervention received.
Overall
Some concerns
Categories: Wet AMD