Treatment of geographic atrophy by the topical administration of OT-551: results of a phase II clinical trial

Abstract

Purpose: To investigate the safety and preliminary efficacy of OT-551, a disubstituted hydroxylamine with antioxidant properties, for the treatment of geographic atrophy (GA), the advanced atrophic form of age-related macular degeneration (AMD).

Methods: The study was a single-center, open-label phase II trial, enrolling 10 participants with bilateral GA. Topical 0.45% OT-551 was administered in one randomly assigned eye three times daily for 2 years. Safety measures were assessed by complete ophthalmic examination, fundus photography, and review of symptoms. The primary efficacy outcome measure was the change in best corrected visual acuity at 24 months. Secondary efficacy measures included changes in area of GA, contrast sensitivity, microperimetry measurements, and total drusen area from baseline.

Results: Study drug was well tolerated and was associated with few adverse events. The mean change in BCVA at 2 years was +0.2 ± 13.3 letters in the study eyes and -11.3 ± 7.6 letters in fellow eyes (P = 0.0259). However, no statistically significant differences were found between the study and fellow eyes for all other secondary outcome measures.

Conclusions: OT-551 was well tolerated by study participants and was not associated with any serious adverse effects. Efficacy measurements in this small study indicate a possible effect in maintaining visual acuity. However, the absence of significant effects on other outcomes measures in this study suggests that OT-551, in the current concentration and mode of delivery, may have limited or no benefit as a treatment for GA (ClinicalTrials.gov number, NCT00306488).

Figure 1.

Baseline GA lesion area and visual acuity in the study and fellow eyes. Baseline GA areas, as measured on CFPs (A) and HRA FAF (B) correlated positively between the study and fellow eyes. Baseline visual acuity in the study and fellow eyes did not show a similar correlation (C).

Figure 2.

Change in visual acuity measurements in the study and fellow eyes from baseline in all participants completing 104 weeks (2 years) of study follow-up (n = 10). (A) Change in visual acuity from baseline for each participant (indicated by P1, P2, and so forth) at 104 weeks for the study and fellow eyes. The study eyes in P5 and P11 maintained baseline acuity. (B) Mean change in visual acuity at 24, 52, 76, and 104 weeks after baseline (P values indicate results of a two-tailed paired t-tests). (C) Proportion of the study and fellow eyes experiencing a 5-letter or greater vision loss from baseline at 104 weeks. (D) Proportion of the study and fellow eyes experiencing a 10-letter or greater vision loss from baseline at 104 weeks.

Figure 3.

Mean change in contrast sensitivity from baseline as measured by the Pelli-Robson chart in the study and fellow eyes at 52 and 104 weeks.

Figure 4.

Change in microperimetry test parameters in the study and fellow eyes from baseline in all participants completing microperimetry evaluation (n = 8). (A) Change in the number of scotomatous points from baseline for each participant (indicated by P1, P2, and so forth) at 104 weeks in the study and fellow eyes. (B) The mean change in the number of scotomatous points at 24, 52, 76, and 104 weeks after baseline. (C) Change in the mean retinal sensitivity of nonscotomatous points from baseline for each participant. (D) Mean change in retinal sensitivity of nonscotomatous points at 24, 52, 76, and 104 weeks after baseline. P values indicate results of two-tailed paired t-tests.

Figure 5.

Change in GA area measurements in the study and fellow eyes from baseline for all participants completing 104 weeks (2 years) of study follow-up (n = 10). (A, B) Change in GA area from baseline in each participant (indicated by P1, P2, and so forth) at 104 weeks in the study and fellow eyes, as measured from CFPs (A) and HRA FAF (B). (C, D) Mean increase in GA area at 24, 52, 76, and 104 weeks after baseline as measured from CFPs (C) and HRA FAF (D). (E, F) Mean percentage increase in GA area at 24, 52, 76, and 104 weeks after baseline as measured from CFPs (E) and HRA FAF (F). P values indicate results of two-tailed paired t-tests.

Figure 6.

Change in total drusen area in the study and fellow eyes from baseline for all participants completing 104 weeks (2 years) of study follow-up (n = 10). (A) Percentage change in visual acuity from baseline for each participant (indicated by P1, P2, and so forth) at 104 weeks for study and fellow eyes. (B) Mean total drusen area at 24, 52, 76, and 104 weeks after baseline. (C) Mean and (D) percentage changes in total drusen at 24, 52, 76, and 104 weeks after baseline. P values indicate results of a two-tailed paired t-test.