Clinical proof of concept for anti-FGF2 therapy in exudative age-related macular degeneration (nAMD): phase 2 trials in treatment-naïve and anti-VEGF pretreated patients
NCT04200248, NCT04640272, NCT04895293 | TOFU, RAMEN, TEMPURA | Pereira DS (2024)
Pereira, D. S., Maturi, R. K., Akita, K., Mahesh, V., Bhisitkul, R. B., Nishihata, T., et al. Clinical proof of concept for anti-FGF2 therapy in exudative age-related macular degeneration (nAMD): phase 2 trials in treatment-naïve and anti-VEGF pretreated patients. Eye, 2024; 38:1140–1148.
Locations
United States and Japan
Study Period
December 2019 – December 2021
Study Design
Phase 2, multicenter, randomized, controlled trial (TOFU) and open-label investigator-sponsored trials (RAMEN, TEMPURA)
Study Population
Experimental Group
Control Group
Follow-up Time: 20 weeks
Outcomes
Durability
Not reported
Vision
Best-Corrected Visual Acuity (BCVA)
Mean BCVA change at Week 16 (Primary Outcome):
• Umedaptanib pegol = -4.8 ± 2.2 letters
• Aflibercept = +2.2 ± 1.9 letters
• Difference = -7.0 letters (95% CI: -11.4 to -2.6, p = 0.016).
Proportion of Patients Gaining ≥10 Letters
At Week 16:
• Umedaptanib pegol: 12.1%
• Aflibercept: 19.3%
• Difference = -7.2% (p = 0.18).
Other
N/A
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Change in Central Subfield Thickness (CST)
Mean CST change at Week 16:
• Umedaptanib pegol = +37.1 ± 15.2 µm
• Aflibercept = -19.4 ± 13.2 µm
• Difference = +56.5 µm (95% CI: 23.8 to 89.2, p = 0.006).
Safety
Treatment-emergent AEs (TEAEs)
Subjects with at least one TEAE:
• Umedaptanib pegol: 75.0%
• Aflibercept: 51.7%
Subjects with at least one Ocular TEAE:
• Umedaptanib pegol: 57.1%
• Aflibercept: 34.5%
Serious Ocular AEs
Subjects with at least one serious TEAE:
• Umedaptanib pegol: 10.7%
• Aflibercept: 10.3%.
Non-ocular AEs
Subjects with at least one Non-ocular TEAE:
• Umedaptanib pegol: 46.4%
• Aflibercept: 31.0%.
Study drug-related AEs
Subjects with at least one Non-ocular TEAE:
• Umedaptanib pegol: 10.7%
• Aflibercept: 0.0%.
Conclusion
Umedaptanib pegol showed bioactivity but was not superior to aflibercept in pretreated nAMD patients. It demonstrated potential efficacy in treatment-naïve nAMD patients in the TEMPURA study. Further trials are needed.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: “Block randomization with randomly selected block sizes (3 or 6) is used. Only the study randomizer will know the true block sizes.” “Baseline demographic features were balanced between treatment groups…”
Missing Outcome Data
Some concerns
Note: There is no evidence that the result was not biased by missing outcome data. However, as the missingness is balanced among the groups, there is unlikely the missingness will impact the outcome.
Selection of the Reported Results
Low risk Note: Registration with protocol.
Deviations from Intended Observations
High risk Note: This is an open-labeled study. However, the assessment of the outcome unlikely can be influenced by knowledge of intervention received. Besides, no ITT or mITT was applied for the data analysis for the primary outcome. However, the total missingness was 11.7% (>5%). Therefore, there is potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized.
Measurement of the Outcome
Some concerns Note: This is an open-label study. In addition, 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. However, the assessment of the outcome unlikely have been influenced by knowledge of intervention received.
Overall
High risk
Categories: Wet AMD