A Study of the Efficacy and Safety of Ranibizumab Injection in Patients With Macular Edema Secondary to Central Retinal Vein Occlusion (CRUISE)

Study Type: Phase III, multicenter, randomized, double-masked, sham injection-controlled (Interventional)

Purpose: Compare efficacy and safety of intravitreal ranibizumab compared with sham injections in patients with macular edema secondary to central retinal vein occlusion (CRVO) – (Treatment)

3 Intervention Groups: single dose regimen given every month (Day 0 through the Month 5 visit for a total of 6 injections

  • Sham injection
  • Ranibizumab injection 0.3 mg
  • Ranibizumab injection 0.5 mg

Participants: 392 patients (Male and female; ≥ 18 years with CRVO at 95 investigational sites in the United States)

  • Sham injection: 130 started, 115 completed (88.5%)
  • Ranibizumab 0.3 mg: 132 started, 129 completed (97.7%)
  • Ranibizumab 0.5 mg: 130 started, 119 completed (91.5%)

Outcome:

  • Primary – Mean change from baseline in BCVA (based on Early Treatment Diabetic Retinopathy Study, ETDRS, visual acuity letters and assessed at a starting distance of 4 meters)
    • Sham injection: 49.2 baseline, 0.8 mean change
    • Ranibizumab injection 0.3 mg: 47.4 baseline, 12.7 mean change
    • Ranibizumab injection 0.5 mg: 48.1 baseline, 14.9 mean change
  • Secondary

    • BCVA
    • Percentage of participants who gained ≥ 15 letters in BCVA score at month 6 compared with baseline
      • Sham injection: 16.9
      • Ranibizumab injection 0.3 mg: 46.2
      • Ranibizumab injection 0.5 mg: 47.7
    • Percentage of participants who lost < 15 letters in BCVA score at month 6 compared with baseline
      • Sham injection: 84.6
      • Ranibizumab injection 0.3 mg: 96.2
      • Ranibizumab injection 0.5 mg: 98.5
    • Central Foveal Thickness - A central reading center assessed all optical coherence tomography (OCT) images. Central foveal thickness was defined as the center point thickness.
    • Percentage of participants with a central foveal thickness of ≤ 250 um at month 6
      • Sham injection: 23.1
      • Ranibizumab injection 0.3 mg: 75.0
      • Ranibizumab injection 0.5 mg: 76.9
    • Mean absolute change from baseline in central foveal thickness at month 6

      • Sham injection: 687.0 baseline, -167.7 mean absolute change
      • Ranibizumab injection 0.3 mg: 679.9 baseline, -433.7 mean absolute change
      • Ranibizumab injection 0.5 mg: 688.7 baseline, -452.3 mean absolute change
    • NEI VFQ-25 - The NEI VFQ-25 (v. 2000; Interviewer Format) consisted of the base set of 25 questions, plus the optional additional questions (where questions A3, A4, and A5 pertained to the Near Activities Subscale; questions A6, A7, and A8 pertained to the Distance Activities Subscale). Scores ranged from 0 to 100; a higher score represented better functioning.

    • Mean change from baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) near activities subscale score at month 6
      • Sham injection: 69.9 baseline, 5.1 change from baseline
      • Ranibizumab injection 0.3 mg: 71.2 baseline, 10.2 change from baseline
      • Ranibizumab injection 0.5 mg: 70.7 baseline, 9.3 change from baseline
    • Mean change from baseline in the NEI FVQ-25 distance activities subscale score at 6 months
      • Sham injection: 77.0 baseline, 2.8 change from baseline
      • Ranibizumab injection 0.3 mg: 77.3 baseline, 8.9 change from baseline
      • Ranibizumab injection 0.5 mg: 77.0 baseline, 6.7 change from baseline

Summary: Subjects who received the Ranibizumab injection saw significantly more improvement in BCVA, central foveal thickness, and the NEI FVQ-25 questionnaire versus those who did not. Those with the 0.5 mg Ranibizumab saw more improvement in BCVA, while those with the 0.3 mg Ranibizumab saw more improvement in central foveal thickness and the NEI FVQ-25 questionnaire.