A prospective, randomized, parallel group, double-blind, multicenter study to compare the efficacy, safety and immunogenicity of Lupin’s Ranibizumab with Lucentis® in patients with neovascular age-related macular degeneration
CTRI/2019/03/018322 | Not reported | Singh R et al. (2022)
Singh, R., Chauhan, R., Saxena, A., Shah, A., Mondal, L., Bakhle, D., Shah, C., Shah, A., Deoghare, S., Krishnan, N., Godse, N. A prospective, randomized, parallel group, double-blind, multicenter study to compare the efficacy, safety and immunogenicity of Lupin’s Ranibizumab with Lucentis® in patients with neovascular age-related macular degeneration. Indian J Ophthalmol, 2022; 70(8):3008-3014.
Locations
19 centers in India
Study Period
June 2019 – October 2020
Study Design
Phase 3, multicenter, randomized, double-blind, parallel-group trial
Study Population
Experimental Group
Control Group
Follow-up Time: 3 months
Outcomes
Durability
Not reported
Vision
Vision Maintaining
The proportion of Patients Losing <15 Letters (Primary Outcome) at Month 3:
• Lupin = 100%
• Lucentis = 98.8%
• Difference = 1.0% (95% CI: -3.3% to 5.4%) is within the predefined equivalence margin of 8.5%
Best-corrected visual acuity (BCVA)
Mean Change in BCVA (ETDRS Letters) from baseline to Month 3:
• Lupin = +8.9
• Lucentis = +7.6
• Difference = 1.33 (95% CI: -1.39 to 4.04, p = 0.338)
Other
N/A
Immunognicity
Positive anti-drug antibodies (ADA) at any time point during the study:
• Lupin = 4.95%
• Lucentis = 12.87%
Pharmokinetics
Not reported
Anatomic
Not reported
Safety
Treatment-emergent AEs (TEAEs)
Total events:
• Lupin: 18
• Lucentis: 31
Ocular-related TEAEs
Total events:
• Lupin: 8
• Lucentis: 15
Patients having at least one ocular TEAE in the study eye:
• Lupin: 2 (1.98%)
• Lucentis: 3 (2.97%)
Patients having at least one ocular TEAE in the fellow eye:
• Lupin: 4 (3.96%)
• Lucentis: 5 (4.95%)
Non-ocular AEs
Total events:
• Lupin: 10
• Lucentis: 16
Patients having at least one non‑ocular TEAE:
• Lupin: 6 (5.94%)
• Lucentis: 14 (13.86%)
Serious TEAEs
Total events:
• Lupin: 1
• Lucentis: 1
Conclusion
Lupin’s Ranibizumab demonstrated therapeutic equivalence to Lucentis® in terms of visual outcomes and safety, with a numerically lower immunogenicity rate.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: “…the randomization list produced by interactive web recognition system (IWRS). This randomization list was not accessible to the investigators or participants involved in the study.” “The demographics and baseline characteristics were comparable between the treatment groups.”
Missing Outcome Data
Low risk
Note: The evidence that the result was not biased by missing outcome data: Analysis based on per protocol (PP) population data was performed as sensitivity analysis.
Selection of the Reported Results
Low risk Note: Registration with the protocol.
Deviations from Intended Observations
Low risk Note: This is a double-blinded study. ITT principle was applied for the primary outcome analysis.
Measurement of the Outcome
Some concerns Note: This is a double-blinded study. There is no information on whether the primary outcome measurements are different or not for the two groups. In addition, this is a multiple-site study; there may be differences in measurement through various sites. However, the outcome assessors were unaware of the intervention.
Overall
Some concerns
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