Safety and efficacy of intravitreal risuteganib for non-exudative AMD: A multicenter, phase 2a, randomized, clinical trial
NCT03626636 | Not reported | Boyer DS et al. (2021)
Boyer, D. S., Gonzalez, V. H., Kunimoto, D. Y., Maturi, R. K., Roe, R. H., Singer, M. A., Xavier, S., Kornfield, J. A., Kuppermann, B. D., Quiroz-Mercado, H., Aubel, J., Karageozian, H. L., Park, J. Y., Karageozian, V. H., Karageozian, L., Sarayba, M. A., & Kaiser, P. K. Safety and efficacy of intravitreal risuteganib for non-exudative AMD: A multicenter, phase 2a, randomized, clinical trial. Ophthalmic Surg Lasers Imaging Retina, 2021; 52:327-335.
Locations
7 sites in the United States
Study Period
June 23, 2017 to March 5, 2019
Study Design
Phase 2a, prospective, randomized, double-masked, sham-controlled, multicenter clinical trial
Study Population
Experimental Group
Control Group
Follow-up Time: 28 weeks
Outcomes
Durability
Not reported
Vision
Vision Maintaining
Patients gaining ≥ 8 ETDRS from baseline to week 28 (Primary Outcome):
• Risuteganib = 12/25, 48% (95% CI: 27.8% - 68.69%)
• Sham = 1/14, 7.1% (95% CI: 0.18% - 33.87%) at Week 12
• Difference: p=0.013 (two-sided Fisher’s exact test)
Patients gaining ≥ 10 ETDRS from baseline to week 28:
• Risuteganib = 32.0%
• Sham = 7.1% at Week 12
• Difference: p=0.12 (two-sided Fisher’s exact test)
Patients gaining ≥ 15 ETDRS from baseline to week 28:
• Risuteganib = 20.0%
• Sham = 0% at Week 12
• Difference: p=0.14 (two-sided Fisher’s exact test)
Best-Corrected Visual Acuity (BCVA)
Mean BCVA change at 28 weeks:
• Risuteganib = +6.1 letters
• Sham = +2.1 letters
Other
N/A
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Not reported
Safety
Treatment-emergent AEs (TEAEs)
The only ocular treatment-related TEAE was vitreous floaters in control group, which resolved without sequelae
Serious AEs
No serious treatment-related AEs were reported
Ocular-related AEs
2 subjects in the risuteganib group converted to exudative AMD (not considered drug-related)
Conclusion
Risuteganib demonstrated significant BCVA improvement in non-exudative AMD patients with no drug-related serious AEs over a 32-week observation period.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: “Eligible subjects were enrolled by the principal investigator and assigned to the experimental treatment group or sham group by the contract research organization using central electronic data capture randomization.” “The demographics and baseline characteristics were similar between the two treatment groups.”
Missing Outcome Data
High risk
Note: The missingness (4/29=13.8 vs. 1/16=6.25%) is unbalanced: Differences between intervention groups in the proportions of missing outcome data. No sensitivity analysis or other adjustment was supplied.
Selection of the Reported Results
Low risk Note: Registration with protocol.
Deviations from Intended Observations
High risk Note: This is a double-masked study. The per-protocol principle was applied for primary outcome analysis (inappropriate method). The missingness (4/29=13.8 vs. 1/16=6.25%) is unbalanced. In addition, there is a difference between the effects of the experimental and comparator interventions on the outcome. Therefore, there was a substantial impact (on the result) of the failure to analyze participants in the group to which they were randomized
Measurement of the Outcome
Some concerns Note: This is a multiple-site study; the primary outcome measurement may have differences between the different centers. However, “Masked investigators, photographers, and VA technicians examined all subjects every 4 weeks for 32 weeks.”
Overall
High risk
Categories: Dry AMD