2. Academic Validation
  3. A CCR2/5 Inhibitor, PF-04634817, Is Inferior to Monthly Ranibizumab in the Treatment of Diabetic Macular Edema

A CCR2/5 Inhibitor, PF-04634817, Is Inferior to Monthly Ranibizumab in the Treatment of Diabetic Macular Edema

  • Invest Ophthalmol Vis Sci. 2018 May 1;59(6):2659-2669. doi: 10.1167/iovs.17-22731.
Jeremy D Gale 1,  Brian Berger 2,  Steven Gilbert 3,  Serghei Popa 4,  Marla B Sultan 5,  Ronald A Schachar 6,  Douglas Girgenti 5,  Christelle Perros-Huguet 1
Affiliations

Affiliations

  • 1 Inflammation and Immunology Research Unit, Pfizer, Inc., Cambridge, Massachusetts, United States.
  • 2 Retina Research Center, Austin, Texas, United States.
  • 3 Early Clinical Development, Pfizer, Inc., Cambridge, Massachusetts, United States.
  • 4 Department of Rheumatology and Nephrology, State University of Medicine and Pharmacy, N. Testemitanu, Chisinau, Moldova.
  • 5 Global Product Development, Pfizer, Inc., New York, New York, United States.
  • 6 Clinical Affairs, Pfizer Essential Health, Pfizer, Inc., San Diego, California, United States.
PMID: 29847672 DOI: 10.1167/iovs.17-22731
Abstract

Purpose: Ligands for the proinflammatory C-C Chemokine Receptor types 2 and 5 (CCR2 and CCR5) are elevated in the eyes of patients with diabetic macular edema (DME). We evaluated the efficacy and safety of PF-04634817, an oral CCR2/5 dual antagonist, versus intravitreal ranibizumab, in adult subjects with DME.

Methods: In this phase II, randomized, placebo-controlled, double-masked study, eligible subjects (≥18 years of age) had type 1 or 2 diabetes and DME with best-corrected visual acuity (BCVA) of 20/32 or worse (letter score ≤ 78), and up to 20/320 or better (≥24 letter score), in the study eye. Subjects were assigned randomly 1:1 to once-daily (QD) oral PF-04634817 200 mg plus masked sham therapy as placebo or monthly intravitreal ranibizumab 0.3/0.5 mg plus QD oral placebo. The primary objective was to evaluate the efficacy of PF-04634817 compared with ranibizumab in change from baseline in BCVA after 12 weeks in a noninferiority design. Noninferiority was based on BCVA 80% confidence interval (CI): there had to be a less than three letter loss in the PF-04634817 arm compared with the ranibizumab arm.

Results: A total of 199 subjects were randomized. Least squares mean difference in change in BCVA from baseline to week 12 in the study eye for the PF-04634817 arm was -2.41 letters (80% CI: -3.91, -0.91; P = 0.04) compared with ranibizumab. PF-04634817 was well tolerated.

Conclusions: Treatment with oral CCR2/5 receptor dual antagonist PF-04634817 was associated with a modest improvement in BCVA, but did not meet the predefined noninferiority criteria compared with intravitreal ranibizumab.

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