Prospective, Randomized, Multicentre, Open-label, Phase II / III Study to Assess Efficacy and Safety of Ranibizumab 0.5 mg Intravitreal Injections Plus Panretinal Photocoagulation (PRP) Versus PRP in Monotherapy in the Treatment of Subjects With High Risk Proliferative Diabetic Retinopathy.

NCT01941329 | Completed Phase 2

• 1 other identifier: ECR-RET-2013-05
• Study Type: interventional
• Target: 94
• Locations: 4 countries
• Sites: 13

Brief Summary

This study is a prospective, randomized, multicentre, open label study that intents to compare the efficacy and safety of ranibizumab 0.5 mg Intravitreal (ITV) injections plus Panretinal Photocoagulation versus Panretinal Photocoagulation alone in the regression of the neovascularization area in patients with High Risk Proliferative Diabetic Retinopathy over a 12-month treatment period. One of the major complications of the diabetes mellitus is Diabetic Retinopathy (DR), one of the leading causes of visual impairment in working age in industrialized countries. Longer diabetes duration and poor glycaemic and blood pressure control are strongly associated with Diabetic Retinopathy. The overall prevalence of any form of Diabetic Retinopathy is 34.4% and 6.96% corresponds to Proliferative Diabetic Retinopathy (PDR). Therefore, approximately 93 million people have Diabetic Retinopathy and 17 million of them have Proliferative Diabetic Retinopathy. It has been shown that treatment with repeated injections of ranibizumab can improve visual acuity in patients with PDR. Further, , the standard PRP treatment of PDR remains unsatisfactory. The knowledge of the mechanisms of this retinal complication is incomplete and, therefore, efforts should be done to understand and characterize patients' eyes response to combined treatments. Therefore, the purpose of this study is to compare the standard treatment for PDR (i.e. Panretinal Photocoagulation) with Panretinal Photocoagulation treatment combined with ITV injections of ranibizumab since it is expected that anti-vascular endothelial growth factor (VEGF) treatment with ITV injections will increase the rate of success of Panretinal Photocoagulation in regression of neovascularization with improved final visual acuity.

Conditions

High Risk Proliferative Diabetic Retinopathy

Keywords

Diabetes; Proliferative Retinopathy; Ranibizumab; Panretinal Photocoagulation

Outcome Measures

Primary Outcomes (1)

• Regression of neovascularization

  Defined as any decrease in the area of neovascularization

  12-month treatment

Secondary Outcomes (7)

• Changes in Best Corrected Visual Acuity (BCVA)

  12-Month treatment

• Time to complete neovascularization regression

  12-Month treatment

• Recurrence of neovascularization

  12-Month treatment

• Macular retinal thickness

  12-Month treatment

• Need of treatment for Diabetic Macular Edema

  12-Month treatment

Study Arms (2)

Ranimizumab + Panretinal photocoagulation (PRP)

EXPERIMENTAL

3 Intravitreous injections of ranibizumab combined with standard PRP (2 ± 1 weeks after injection), at month-0, month-1 and month-2 that can be repeated after month-3, with always at least 1 month of interval between injections.

Procedure: Panretinal Photocoagulation (PRP); Drug: Intravitreous injection of ranibizumab

Panretinal photocoagulation (PRP)

ACTIVE COMPARATOR

Panretinal photocoagulation treatment (PRP) between month-0 and month-2, with 1 mandatory laser session in month-0 and more laser sessions as needed until Month-2 to complete the PRP treatment. After completing the PRP treatment, PRP sessions can be repeated from Month-3 to Month-11.

Procedure: Panretinal Photocoagulation (PRP)

Interventions

Panretinal Photocoagulation (PRP) PROCEDURE

Panretinal photocoagulation (PRP); Ranimizumab + Panretinal photocoagulation (PRP)

Intravitreous injection of ranibizumab DRUG

Ranimizumab + Panretinal photocoagulation (PRP)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• High-risk proliferative diabetic retinopathy (HR-PDR); Neovascularization in the disc (NVD) ≥ 1/4 disc area (DA) OR Neovascularization elsewhere (NVE) ≥ 1/2 DA; NVE \< 1/2 DA + vitreous and/or pre-retinal haemorrhage and/or rubeosis; NVD \<1/4 DA + vitreous and/or pre-retinal haemorrhage and/or rubeosis;
• BCVA at baseline ≥ 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters score (approximate Snellen equivalent 20/320);
• Type I or Type II diabetic subjects of either gender;
• Age ≥ 18 years;
• Ability to provide written informed consent;
• Ability to return for all clinical trial visits;

You may not qualify if:

• Any intraocular surgery within 6 months before trial enrolment, including:
• Prior scatter (panretinal) or focal/grid photocoagulation; Eyes who have received yttrium aluminum garnet (YAG) laser, or peripheral retinal cryoablation, or laser retinopexy (for retinal tears only);
• Fibrovascular proliferation with retinal traction;
• Other cause of retinal NV (retinal vein occlusion, radiation retinopathy or others);
• Atrophy/scarring/fibrosis/ hard exudates involving the centre of the macula;
• Significant media opacities or inadequate pupillary dilation, which might interfere with visual acuity, assessment of toxicity or fundus photography;
• Any likelihood that the subject will require cataract surgery within the following 1 year;
• Diabetic macular edema (DME) with central involvement, i.e., central macular thickness (Central Point Thickness) \> 300 µm (Stratus OCT) equivalent values measured by spectral domain (SD)-OCT, adjusted according to the SD-OCT machine used;
• Previous vitrectomy;
• Intraocular pressure \> 21 mmHg;
• Previous anti-VEGF therapy within the last 3 months;
• Known serious allergies or history of hypersensitivity to fluorescein used in angiography, or to components of Lucentis® formulation;
• Acute ocular or periocular infection;
• Systolic BP \> 170 mmHg or diastolic BP \> 100 mmHg;
• HbA1C level \>11% or recent signs of uncontrolled diabetes;

Sponsors & Collaborators

• Association for Innovation and Biomedical Research on Light and Image: lead
• European Vision Institute Clinical Research Network: collaborator

Study Sites (13)

Department of Ophthalmology, University Hospital, CHU Dijon

Dijon, 21033, France

Location

Department of Ophthalmology, Lariboisière Hospital

Paris, 75475, France

Location

Centre d'Investigation Clinique - Centre National d'Ophtalmologie des Quinze-Vingts

Paris, 75571, France

Location

Department of Ophthalmology, University Vita Salute - Scientific Institute of San Raffael

Milan, 20132, Italy

Location

Centre for Clinical Trials, Department of Ophthalmology, University of Padova

Padua, 35128, Italy

Location

G.B.Bietti Eye Foundation - IRCCS

Rome, 00198, Italy

Location

Centre for Clinical Trials - Association for Innovation and Biomedical Research on Light and Image

Coimbra, 3000-548, Portugal

Location

Espaço Médico de Coimbra

Coimbra, 3030-163, Portugal

Location

Instituto de Retina de Lisboa

Lisbon, 1050-085, Portugal

Location

Serviço de Oftalmologia,Hospital de Vila Franca de Xira

Vila Franca de Xira, 2600-009, Portugal

Location

Ophthalmology Clinical Trials Unit Frimley Park Hospital Foundation Trust

Frimley, GU16 7UJ, United Kingdom

Location

Clinical Trial Unit, Dep. Ophth., Gloucestershire Hospitals NHS Foundation Trust

Gloucestershire, GL53 7PX, United Kingdom

Location

Laser and Retinal Research Unit, King's Health Partners

London, SE5 9RS, United Kingdom

Location

MeSH Terms

Conditions

Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• José Cunha-Vaz, MD, PhD

  Association of Innovation and Biomedical Research on Light and Image

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2013
• First Posted: September 13, 2013
• Study Start: April 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: October 1, 2017
• Last Updated: May 14, 2018

Record last verified: 2018-05

Locations

PT (4); GB (3); FR (3); IT (3)