Elsevier

Ophthalmology

Volume 112, Issue 10, October 2005, Pages 1747-1757
Ophthalmology

Original Article
A Phase II Randomized Double-Masked Trial of Pegaptanib, an Anti–Vascular Endothelial Growth Factor Aptamer, for Diabetic Macular Edema

Study results presented in part at: Association for Research in Vision and Ophthalmology annual meeting, May 1–5, 2005; Fort Lauderdale, Florida.
https://doi.org/10.1016/j.ophtha.2005.06.007Get rights and content

Objective

To evaluate the safety and efficacy of pegaptanib sodium injection (pegaptanib) in the treatment of diabetic macular edema (DME).

Design

Randomized, double-masked, multicenter, dose-ranging, controlled trial.

Participants

Individuals with a best-corrected visual acuity (VA) between 20/50 and 20/320 in the study eye and DME involving the center of the macula for whom the investigator judged photocoagulation could be safely withheld for 16 weeks.

Intervention

Intravitreous pegaptanib (0.3 mg, 1 mg, 3 mg) or sham injections at study entry, week 6, and week 12 with additional injections and/or focal photocoagulation as needed for another 18 weeks. Final assessments were conducted at week 36.

Main Outcome Measures

Best-corrected VA, central retinal thickness at the center point of the central subfield as assessed by optical coherence tomography measurement, and additional therapy with photocoagulation between weeks 12 and 36.

Results

One hundred seventy-two patients appeared balanced for baseline demographic and ocular characteristics. Median VA was better at week 36 with 0.3 mg (20/50), as compared with sham (20/63) (P = 0.04). A larger proportion of those receiving 0.3 mg gained VAs of ≥10 letters (approximately 2 lines) (34% vs. 10%, P = 0.003) and ≥15 letters (18% vs. 7%, P = 0.12). Mean central retinal thickness decreased by 68 μm with 0.3 mg, versus an increase of 4 μm with sham (P = 0.02). Larger proportions of those receiving 0.3 mg had an absolute decrease of both ≥100 μm (42% vs. 16%, P = 0.02) and ≥75 μm (49% vs. 19%, P = 0.008). Photocoagulation was deemed necessary in fewer subjects in each pegaptanib arm (0.3 mg vs. sham, 25% vs. 48%; P = 0.04). All pegaptanib doses were well tolerated. Endophthalmitis occurred in 1 of 652 injections (0.15%/injection; i.e., 1/130 [0.8%] pegaptanib subjects) and was not associated with severe visual loss.

Conclusions

In this phase II trial, subjects assigned to pegaptanib had better VA outcomes, were more likely to show reduction in central retinal thickness, and were deemed less likely to need additional therapy with photocoagulation at follow-up.

Section snippets

Study Design

This study was a randomized, controlled, double-masked, parallel-group, dose-finding, phase II trial. Patients with DME were enrolled at 39 sites. The study was conducted in conformance with the principles of the Declaration of Helsinki and with the laws of the country in which the research was conducted. Institutional review board or ethics committee approval was obtained at all sites, and each patient provided signed informed consent before study entry.

Subject Selection

Patients 18 years or older of either

Results

All 172 randomized subjects (0.3 mg, n = 44; 1 mg, n = 44; 3 mg, n = 42; sham, n = 42) were included in the intention-to-treat analyses; data were missing for 1 patient each in the 1-mg and sham groups. A total of 169 individuals received at least one study treatment and were included in the safety analyses (0.3 mg, n = 44; 1 mg, n = 42; 3 mg, n = 42; sham, n = 41). Baseline demographic and ocular characteristics were well balanced across all treatment groups (Table 1). More than 90% of study

Discussion

The totality of our results suggests an overall VA gain as well as a reduced risk of VA loss in eyes with DME (as recognized on OCT) treated with intravitreous pegaptanib. The 0.3-mg dose seemed to be the most efficacious dose studied. Outcomes appeared to favor the 0.3-mg dose with respect to mean VA, greater decrease in retinal thickness, and less need for focal/grid laser intervention. Due to the relatively small number of participants in the study, however, we were unable to identify

References (27)

  • The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus

    N Engl J Med

    (1993)
  • I.M. Stratton et al.

    UKPDS 50risk factors for incidence and progression of retinopathy in type II diabetes over 6 years from diagnosis

    Diabetologia

    (2001)
  • R. Klein et al.

    The Wisconsin Epidemiologic Study of Diabetic Retinopathy III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years

    Arch Ophthalmol

    (1984)
  • Cited by (552)

    View all citing articles on Scopus

    Manuscript no. 2005-273.

    The study was sponsored by Eyetech Pharmaceuticals, Inc., New York, New York, and Pfizer Inc., New York, New York.

    [email protected]

    For names of members of the Study Group taking authorship responsibility for this article and who had complete access to the data needed for this report, and pertinent financial conflicts of interest, see “Appendix.”

    View full text