Phase III clinical study to evaluate the efficacy, expressed as improvement in visual acuity in patients suffering diabetic macular edema after one year of treatment with PRO-169, compared to treatment with Lucentis® (ranibizumab).
A total of 442 patients with diabetic macular edema will be randomized 1:1 to be treated with either PRO-169 (bevacizumab) or Lucentis® (ranibizumab). There will be a total of 14 visits, including selection and final visits. Monthly evaluations will include ophthalmologic evaluations of anterior and posterior segments, as well as OCT (optic coherence tomography) to obtain central macular width and retinal volume. Fluorescein angiography will be performed on selection visit as well as 6 and 12 months into the study (visits 7 and 13). All patients will be exposed to intravitreal injection of either of the studied drugs monthly for the first 4 months. Starting on visit 5 patients will be injected depending on their response to treatment, calculated according predetermined algorithms including clinical and image variables. Starting on month 6, patients may be subjected to rescue therapy with photocoagulation if they comply with predetermined criteria for such measure.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
509
Administration of monthly intravitreal bevacizumab (4-12 injections)
Administration of monthly intravitreal ranibizumab (4-12 injections)
SalaUno Salud, S.A.P.I. de C.V.
Mexico City, Mexico City, Mexico
Best Corrected Visual Acuity
Best Corrected Visual Acuity will be evaluated according the standardized ETDRS. The mean change between two treatments will be used evaluated as difference between baseline and final (12 months) values.
Time frame: Day 30±3 (Visit 2), Day 60±3 (Visit 3), Day 90±3 (Visit 4), Day 120±3 (Visit 5), Day 150±3 (Visit 6), Day 180±3 (Visit 7), Day 210±3 (Visit 8), Day 240±3 (Visit 9), Day 270±3 (Visit 10), Day 300±3 (Visit 11), Day 330±3 (Visit 12), Day 360±3 (Final Visit)
Best Corrected Visual Acuity Area Under the Curve
Best Corrected Visual Acuity will be evaluated according the standardized ETDRS. The area under the curve of both treatments will be used evaluated as difference between baseline and final (12 months) values.
Time frame: Day 30±3 (Visit 2), Day 60±3 (Visit 3), Day 90±3 (Visit 4), Day 120±3 (Visit 5), Day 150±3 (Visit 6), Day 180±3 (Visit 7), Day 210±3 (Visit 8), Day 240±3 (Visit 9), Day 270±3 (Visit 10), Day 300±3 (Visit 11), Day 330±3 (Visit 12), Day 360±3 (Final Visit)
Best Corrected Visual Acuity
Best Corrected Visual Acuity will be evaluated according the standardized ETDRS. The corrected BCVA (adjusted to baseline value) of both treatments will be used evaluated at 4 months. The value was obtained from the value obtained on day 120 minus the baseline value.
Time frame: Day 120±3 (Visit 5)
Central Macular Thickness
Central macular thickness will be evaluated through OCT scan. The mean change between two treatments will be used evaluated as difference between baseline and final (12 months) values.
Time frame: Day 30±3 (Visit 2), Day 60±3 (Visit 3), Day 90±3 (Visit 4), Day 120±3 (Visit 5), Day 150±3 (Visit 6), Day 180±3 (Visit 7), Day 210±3 (Visit 8), Day 240±3 (Visit 9), Day 270±3 (Visit 10), Day 300±3 (Visit 11), Day 330±3 (Visit 12), Day 360±3 (Final Visit)
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Retinal Volume
Retinal volume will be evaluated through OCT scan. The mean change between two treatments will be used evaluated as difference between baseline and final (12 months) values.
Time frame: Day 30±3 (Visit 2), 60±3 (Visit 3), 90±3 (Visit 4), 120±3 (Visit 5), 150±3 (Visit 6), 180±3 (Visit 7), 210±3 (Visit 8), 240±3 (Visit 9), 270±3 (Visit 10), 300±3 (Visit 11), 330±3 (Visit 12), 360±3 (Final Visit)
Percentage of Patients With a Positive Response to Treatment.
Determining the percentage of patients with a positive response to treatment, considered as: absolute improvement (20/20 vision for two consecutive visits and central macular thickness \< 300 μm in men and \< 290 μm in women), improvement (one or more of the following: patient who gained 5 or more letters for BCVA, ≥ 10% decrease of macular central thickness value compared to last two visits) and stability (one or more of the following: patient with neither a gain of 5 or more letters for BCVA nor a ≥ 10% decrease of macular central thickness value compared to last two visits, patient without loss of 5 or more letters for BCVA or a ≥ 10% decrease of macular central thickness value compared to last visit).
Time frame: Day 120±3 (Visit 5), Day 150±3 (Visit 6), Day 180±3 (Visit 7), Day 210±3 (Visit 8), Day 240±3 (Visit 9), Day 270±3 (Visit 10), Day 300±3 (Visit 11), Day 330±3 (Visit 12), Day 360±3 (Final Visit)
Mean Number of Injections
Determining the mean number of injections applied during study, comparing both arms.
Time frame: Day 30±3 (Visit 2), Day 60±3 (Visit 3), Day 90±3 (Visit 4), Day 120±3 (Visit 5), Day 150±3 (Visit 6), Day 180±3 (Visit 7), Day 210±3 (Visit 8), Day 240±3 (Visit 9), Day 270±3 (Visit 10), Day 300±3 (Visit 11), Day 330±3 (Visit 12), Day 360±3 (Final Visit)
Frequency of Rescue Therapy Administration
Number of patients who required photocoagulation treatment
Time frame: Day 30±3 (Visit 2), Day 60±3 (Visit 3), Day 90±3 (Visit 4), Day 120±3 (Visit 5), Day 150±3 (Visit 6), Day 180±3 (Visit 7), Day 210±3 (Visit 8), Day 240±3 (Visit 9), Day 270±3 (Visit 10), Day 300±3 (Visit 11), Day 330±3 (Visit 12), Day 360±3 (Final Visit)
Adverse Events Related to the Injection
This section describes the treatment-related adverse events reported throughout the study
Time frame: Day 360±3 (Final Visit)
Ophthalmic Drug-related Adverse Events
The number of adverse events related to the eyes associated with the medication is described.
Time frame: Day 360±3 (Final Visit)
Systemic Drug-related Adverse Events
The number of treatment-related adverse events at the systemic level is described
Time frame: Day 360±3 (Final Visit)