Multicenter Randomized Open-label Three-arms Controlled 12 Months Clinical Proof of Concept Study to Evaluate Efficacy and Safety of Ranibizumab Alone or in Combination With Laser Photocoagulation vs. Laser Photocoagulation Alone in Proliferative Diabetic Retinopathy
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 107
- Locations
- 1
- Primary Endpoint
- Change From Baseline in Area of Neovascularizations (NVs) at End of Core Study (EOCS)
Study Overview
Brief Summary
The purpose of this study was to assess the efficacy and safety of the anti-Vascular Endothelial Growth Factor (VEGF) agent ranibizumab (0.5 mg) with or without Panretinal laser photocoagulation (PRP) compared to PRP alone in patients with Proliferative Diabetic Retinopathy (PDR).
Detailed Description
A 12-month core phase was followed by a 12-month observational follow-up phase (physician's routine), for a planned individual study duration of 24-25 months. A separate informed consent was signed for the 12-month observational follow-up phase. This study was conducted in Germany.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Masking Description
An open-label design was chosen in which the evaluation of the primary objective was performed by a reading center. The reading center that evaluated the primary and several secondary objectives was blinded to randomization and therefore assessed these objectives uninfluenced by treatment information. However, laser burns were visible on the images, and no full blinding regarding panretinal laser photocoagulation (PRP) was possible for the reading center.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Proliferative Diabetic Retinopathy
- •Best Corrected Visual Acuity (BCVA) in study eye of at least 20 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/400)
- •Type 1 or type 2 diabetes under medical surveillance / with stabilized treatment
Exclusion Criteria
- •Proliferative vitreoretinopathy in study eye
- •Clinically significant macular edema (CSME) in the study eye
- •Clinically non significant macular edema (CNSME) that is likely to develop to CSME in the study eye
- •Uncontrolled glaucoma in either eye
- •Other protocol-specified conditions
Arms & Interventions
Ranibizumab mono
Interventional Core Phase: One intravitreal injection of ranibizumab 0.5 mg to the study eye monthly until stability regarding morphological parameters is confirmed (ie, no further improvement of morphology or no worsening of morphology for 3 consecutive months)
Intervention: Ranibizumab 0.5 mg (Drug)
PRP mono
Interventional Core Phase: Panretinal laser photocoagulation (PRP) treatment administered to the study eye in accordance with the modified diabetic retinopathy study (DRS) guidelines for panretinal laser photocoagulation procedures
Intervention: Panretinal laser photocoagulation (Procedure)
Ranibizumab+PRP
Interventional Core Phase: Ranibizumab 0.5 mg as described for the ranibizumab mono arm and PRP treatment as described for the PRP mono arm until stability regarding morphological parameters is confirmed
Intervention: Ranibizumab 0.5 mg (Drug)
Ranibizumab+PRP
Interventional Core Phase: Ranibizumab 0.5 mg as described for the ranibizumab mono arm and PRP treatment as described for the PRP mono arm until stability regarding morphological parameters is confirmed
Intervention: Panretinal laser photocoagulation (Procedure)
Outcomes
Primary Outcomes
Change From Baseline in Area of Neovascularizations (NVs) at End of Core Study (EOCS)
Time Frame: Baseline, EOCS
The area of neovascularizations (NV) was assessed by a central reading center via fluorescein angiography (FA) images. The area of NV was calculated as the sum of area of neovascularization of the disc (NVD) and neovascularization elsewhere (NVE) and was recorded in square millimeters. A higher positive change value may indicate a greater formation of new, abnormal blood vessels and thus disease progression. One eye (study eye) contributed to the analysis.
Secondary Outcomes
- Change From Baseline in Area of Neovascularizations (NVs) at Month 3(Baseline, Month 3)
- Number of Patients With Change From Baseline in ETDRS Severity Grade of Diabetic Retinopathy (DR) at EOCS(Baseline, EOCS)
- Change From Baseline in Central Subfield Thickness at EOCS(Baseline, EOCS)
- Best Corrected Visual Acuity (BCVA) (ETDRS Letters) at EOCS(EOCS)
- Number of Ranibizumab Injections Until EOCS(Baseline to EOCS)
- Number of PRP Laser Spots Until EOCS(Baseline to EOCS)
- Percentage of Patients With Change From Baseline in BCVA (ETDRS Letters) at EOCS(Baseline, EOCS)
- Change From Baseline in Foveal Center Point Retinal Thickness at EOCS(Baseline, EOCS)