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Efficacy and Safety of Ranibizumab 0.5 vs Verteporfin PDT in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia

Phase 3
Completed
Conditions
Visual Impairment Due to Choroidal Neovascularization (CNV) Secondary to Pathologic Myopia (PM)
Interventions
Registration Number
NCT01922102
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

This study was designed to evaluate the efficacy and safety of two different dosing regimens of 0.5 mg ranibizumab given as intravitreal injection in comparison to verteporfin PDT in patients with visual impairment due to choroidal neovascularization secondary to pathologic myopia (PM)

Detailed Description

This was a phase III, multi-center, randomized, double-masked, active-controlled study comparing 0.5 mg ranibizumab vs. vPDT therapy. The study included 15 scheduled visits over 12 months, and there were to be two additional visits (2a, 3a) for subset of patients in whom PK analysis were performed.

There were 3 periods in this study: Screening period-from Day -14 to Baseline; Treatment period-from Baseline to Month 11; Follow-up period-from Month 11 to Month 12 Patients entered the 11 months Treatment period at Visit 2 (Day 1) if eligibility criteria were met and were randomized in three treatment groups Group I ranibizumab 0.5 mg driven by VA stability criteria or Group II ranibizumab 0.5 mg driven by disease activity criteria or Group III vPDT (randomization ratio of 2:2:1) and received first treatment of either a ranibizumab injection and sham vPDT or sham injection and active vPDT and will return to the clinical center within 7 days to undergo safety assessments as well as assessments of the effect of treatment by the evaluating investigator. The following visits were performed at one month intervals starting at Visit 4 and continuing through Visit 14. At all monthly visits (at/from Month 2 for group I, at/from Month 1 for group II and at/from Month 3 for group III) the decision for treatment were made by the evaluating investigator based on the VA stability criteria and on the disease activity criteria. At Month 3 (visit 6) and at all following monthly visits for all three groups one of the three options can recommended by evaluating investigator: a) ranibizumab 0.5 mg, b) ranibizumab 0.5 mg + vPDT; c) vPDT. The treating investigator were then perform treatment based on randomization and masking requirements.

At each monthly visit, patients had a safety evaluation by the evaluating investigator prior to study treatment, consisting of visual acuity measurements, ophthalmic examinations and evaluation of adverse events and vital signs. Routine hematology, chemistry, and urinalysis profiles were obtained at Visit 6, 9 and 12 (Month 3, 6 and 9). At Month 12 several procedures and assessments were performed which are required at study completion visit.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
457
Inclusion Criteria
  • Visual impairment due to CNV secondary to PM.
  • Best corrected visual acuity in the study eye > 24 and < 78 ETDRS letters.
  • High myopia (> -6D),
  • anterio-posterior elongation > 26 mm; posterior changes compatible with the pathologic myopia.
  • Either CNV locations in the study eye: subfoveal, juxtafoveal, extrafoveal.
Exclusion Criteria
  • Some preexisting eye disorders or systemic diseases;-Blood pressure > 150/90 mmHg
  • Prior focal/grid laser to the macular area -History of treatment with any anti-VEGF or verteporfin PDT in the study eye
  • Intravitreal treatment with corticosteroids or intraocular surgery within last 3 months in the study eye

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group IIRanibizumab 0.5 mg0.5 mg ranibizumab driven by disease activity criteria
Group IRanibizumab 0.5mg0.5 mg ranibizumab driven by visual acuity stability criteria
Group IIIVerteporfin PDTverteporfin PDT
Primary Outcome Measures
NameTimeMethod
Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 3From Baseline to Month 3

Best corrected visual acuity (BCVA) was tested using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) charts testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.

Secondary Outcome Measures
NameTimeMethod
The Average Change in BCVA Score From Baseline to Month 1 Through Month 12From Baseline to Month 12

Best corrected visual acuity (BCVA) was tested using the ETDRS VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.

Between treatment comparison of 0.5 mg ranibizumab intravitreal injections driven by disease activity re-treatment criteria (Group II) versus 0.5 mg ranibizumab intravitreal injections driven by visual acuity stability criteria (Group I) based on the average BCVA change from Baseline to Month 1 through Month 12

Mean Change From Baseline in Visual Acuity Over TimeChange from baseline at months 3, 6, and 12

Best corrected visual acuity (BCVA) was tested using the ETDRS VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.

NEI-VFQ-25 - Change From Baseline to Month 3, 6 and 12Change from baseline at month 3, 6 and 12

The VFQ-25 consists of 25 vision related questions across 11 vision related subscales, including general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision and peripheral vision, and a general health rating. Items are converted to a 0-100 scale on each subscale and for the composite score where higher scores represents better functioning.

Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12From Baseline until Month 12

CNV leakage is assessed via fluorescein angiography (center involvement) category: definite, questionable, absent, can't grade, and missing.

Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 6From Baseline to Month 6

Best corrected visual acuity (BCVA) was tested using the early treatment diabetic retinopathy study (ETDRS) VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.

Between treatment comparison of 0.5 mg ranibizumab intravitreal injections driven by disease activity re-treatment criteria (Group II) versus 0.5 mg ranibizumab intravitreal injections driven by visual acuity stability criteria (Group I) based on the average BCVA change from Baseline to Month 1 through Month 6.

Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study EyeFrom Baseline to Month 12

ETDRS VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.

Mean Change From Baseline Over Time in Central Sub-field Thickness (CSFT)Baseline, Month 3, Month 6, and Month 12

Central sub-field thickness (CSFT) is a variable assessed via Optical Coherence Tomography (OCT). OCT was performed prior to any study drug administration to assess presence of intra, subretinal fluid, or increase of CSFT.

Number of Ranibizumab Injections Received in the Study Eye for the Ranibizumab GroupsFrom Baseline to Month 12

To assess treatment pattern with ranibizumab

Trial Locations

Locations (1)

Novartis Investigative Site

🇹🇭

Nakornphathom, Thailand

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