Multicenter 12 Months Clinical Study to Evaluate Efficacy and Safety of Ranibizumab Alone or in Combination With Laser Photocoagulation vs. Laser Photocoagulation Alone in Proliferative Diabetic Retinopathy (PRIDE) (PRIDE)

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

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).

Study Overview

• Status: Completed
• Conditions: Proliferative Diabetic Retinopathy (PDR)
• Intervention / Treatment: Drug: Ranibizumab 0.5 mg; Procedure: Panretinal laser photocoagulation

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 Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • Novartis Investigative Site
  • Augsburg, Germany, 86156
    • Novartis Investigative Site
  • Berlin, Germany, 12203
    • Novartis Investigative Site
  • Darmstadt, Germany, 64297
    • Novartis Investigative Site
  • Duesseldorf, Germany, 40225
    • Novartis Investigative Site
  • Essen, Germany, 45122
    • Novartis Investigative Site
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Glauchau, Germany, 08371
    • Novartis Investigative Site
  • Gottingen, Germany, 37075
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Hösbach, Germany, 63768
    • Novartis Investigative Site
  • Karlsruhe, Germany, 76133
    • Novartis Investigative Site
  • Koeln, Germany, 51109
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Marburg, Germany, 35039
    • Novartis Investigative Site
  • Muenchen, Germany, 81675
    • Novartis Investigative Site
  • Muenster, Germany, 48149
    • Novartis Investigative Site
  • Muenster, Germany, 48145
    • Novartis Investigative Site
  • München, Germany, 80336
    • Novartis Investigative Site
  • Regensburg, Germany, 93042
    • Novartis Investigative Site
  • Tübingen, Germany, 72076
    • Novartis Investigative Site
  • Ulm, Germany, 89075
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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)	Drug: Ranibizumab 0.5 mg; Pre-filled syringe for intravitreal injection; Other Names: Lucentis®; RFB002
Active Comparator: 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	Procedure: Panretinal laser photocoagulation; PRP treatment following DRS guidelines; Other Names: PRP
Experimental: 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	Drug: Ranibizumab 0.5 mg; Pre-filled syringe for intravitreal injection; Other Names: Lucentis®; RFB002; Procedure: Panretinal laser photocoagulation; PRP treatment following DRS guidelines; Other Names: PRP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Area of Neovascularizations (NVs) at End of Core Study (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.	Baseline, EOCS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Area of Neovascularizations (NVs) at Month 3	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.	Baseline, Month 3
Best Corrected Visual Acuity (BCVA) (ETDRS Letters) at EOCS	BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at a testing distance of 4 meters. A higher number of ETDRS letters may indicate better visual acuity. One eye (study eye) contributed to the analysis.	EOCS
Percentage of Patients With Change From Baseline in BCVA (ETDRS Letters) at EOCS	BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at a testing distance of 4 meters. No clinically relevant change was defined as <5 letters gain or loss. A higher positive change value may indicate a greater improvement in visual acuity. One eye (study eye) contributed to the analysis.	Baseline, EOCS
Number of Patients With Change From Baseline in ETDRS Severity Grade of Diabetic Retinopathy (DR) at EOCS	The severity level of diabetic retinopathy was determined using the ETDRS severity scale. However, in contrast to the original ETDRS severity scale, wide field fluorescein angiography images were used in addition to color fundus photography for identification of NVs and prior PRP treatment was not considered for determining the severity level. Eyes could be graded in the following classes: "DR absent" (10), "questionable DR" (14,15), "NPDR" (20-53), "mild PDR" (60-61), "moderate PDR" (65), "high risk PDR" (71-75), "advanced PDR" (81-85) and "cannot grade" (90). One eye (study eye) contributed to the analysis. No statistical analysis was conducted for ≥ 1 class deterioration or ≥ 2 class deterioration from Baseline at EOCS because ratios could not be calculated in case of zero frequencies in at least one of the three treatment groups.	Baseline, EOCS
Change From Baseline in Central Subfield Thickness at EOCS	Central subfield retinal thickness was assessed by a central reading center using Optical Coherence Tomography images. A positive change value may indicate disease progression. One eye (study eye) contributed to the analysis.	Baseline, EOCS
Change From Baseline in Foveal Center Point Retinal Thickness at EOCS	Foveal center point retinal thickness was assessed by a central reading center using Optical Coherence Tomography images. A positive change value may indicate disease progression. One eye (study eye) contributed to the analysis.	Baseline, EOCS
Number of Ranibizumab Injections Until EOCS	The total number of ranibizumab injections until EOCS was calculated. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.	Baseline to EOCS
Number of PRP Laser Spots Until EOCS	The total number of PRP laser spots from baseline until EOCS was calculated. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.	Baseline to EOCS

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2012
• Primary Completion (Actual): November 30, 2016
• Study Completion (Actual): December 5, 2017

Study Registration Dates

• First Submitted: May 3, 2012
• First Submitted That Met QC Criteria: May 7, 2012
• First Posted (Estimate): May 9, 2012

Study Record Updates

• Last Update Posted (Actual): March 15, 2019
• Last Update Submitted That Met QC Criteria: November 20, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Ranibizumab; Panretinal photocoagulation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Diseases; Diabetic Retinopathy; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: CRFB002DDE21; 2011-005542-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No