To Assess the Efficacy and Safety of Intravitreal Ranibizumab in People With Vision Loss Due to Macular Edema

A 12-month, Randomized, Double-masked, Sham-controlled, Multicenter Study to Evaluate the Efficacy and Safety of 0.5mg Ranibizumab Intravtitreal Injections in Patients With Visual Impairment Due to Vascular Endothelial Growth Factor (VEGF)Driven Macular Edema

To evaluate the efficacy and safety of 0.5 mg Ranibizumab intravitreal injections in adult patients with visual impairment due to macular edema (ME).

Study Overview

• Status: Completed
• Conditions: Macular Edema (ME)
• Intervention / Treatment: Drug: Ranibizumab; Other: Sham control

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2000
      • Novartis Investigative Site
    • Westmead, New South Wales, Australia, 2145
      • Novartis Investigative Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Novartis Investigative Site
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Novartis Investigative Site
    • South Launceston, Tasmania, Australia, 7249
      • Novartis Investigative Site
• Belgium
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2E1
      • Novartis Investigative Site
• Czech Republic
  • Plzen, Czech Republic, 301 00
    • Novartis Investigative Site
  • Praha 10, Czech Republic, 100 34
    • Novartis Investigative Site
• France
  • Bordeaux Cedex, France, F-33076
    • Novartis Investigative Site
  • Lyon, France, 69003
    • Novartis Investigative Site
  • Paris cedex 10, France, 75010
    • Novartis Investigative Site
  • Saint-Jean, France, 31240
    • Novartis Investigative Site
• Germany
  • Duesseldorf, Germany, 40225
    • Novartis Investigative Site
  • Freiburg i. Br, Germany, 79106
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Regensburg, Germany, 93042
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1083
    • Novartis Investigative Site
  • Budapest, Hungary, 1133
    • Novartis Investigative Site
  • Debrecen, Hungary, 4012
    • Novartis Investigative Site
  • Szeged, Hungary, H-6720
    • Novartis Investigative Site
• Israel
  • Jerusalem, Israel, 9112001
    • Novartis Investigative Site
  • Kfar-Sava, Israel, 4428164
    • Novartis Investigative Site
  • Petach Tikva, Israel, 49100
    • Novartis Investigative Site
  • Rehovot, Israel, 7610001
    • Novartis Investigative Site
  • Tel-Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • FI
    • Firenze, FI, Italy, 50134
      • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16132
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20123
      • Novartis Investigative Site
  • PI
    • Pisa, PI, Italy, 56124
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00133
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10122
      • Novartis Investigative Site
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 150-034
    • Novartis Investigative Site
  • Korea
    • Seoul, Korea, Korea, Republic of, 03080
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 137-701
      • Novartis Investigative Site
• Latvia
  • Riga, Latvia, 1002
    • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Novartis Investigative Site
  • Tilburg, Netherlands, NL-5022GC
    • Novartis Investigative Site
• Russian Federation
  • Kazan, Russian Federation, 420012
    • Novartis Investigative Site
  • Moscow, Russian Federation, 127486
    • Novartis Investigative Site
  • Moscow, Russian Federation, 119021
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 168751
    • Novartis Investigative Site
• Slovakia
  • Banska Bystrica, Slovakia, 97517
    • Novartis Investigative Site
  • Trencin, Slovakia, 91171
    • Novartis Investigative Site
• Spain
  • Andalucia
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Novartis Investigative Site
  • Castilla y Leon
    • Valladolid, Castilla y Leon, Spain, 47011
      • Novartis Investigative Site
  • Catalunya
    • Sant Cugat, Catalunya, Spain, 08190
      • Novartis Investigative Site
• Switzerland
  • Bern, Switzerland, 3010
    • Novartis Investigative Site
  • Binningen, Switzerland, 4102
    • Novartis Investigative Site
  • Zuerich, Switzerland, 8063
    • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Kocaeli, Turkey, 41380
    • Novartis Investigative Site
• United Kingdom
  • Birmingham, United Kingdom, B18 7QU
    • Novartis Investigative Site
  • Bristol, United Kingdom, BS1 2LX
    • Novartis Investigative Site
  • London, United Kingdom, EC1V 2PD
    • Novartis Investigative Site
  • Manchester, United Kingdom, M13 9WL
    • Novartis Investigative Site
  • Southampton, United Kingdom, SO16 6YD
    • Novartis Investigative Site
  • Sunderland, United Kingdom, SR2 9HP
    • Novartis Investigative Site
  • Surrey
    • Frimley, Surrey, United Kingdom, GU16 7UJ
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of active ME secondary to any causes (for adult patients: except diabetic macular edema (DME), age-related macular degeneration (AMD) and retinal vein occlusion (RVO));
• BCVA must be between ≥ 24 and ≤ 83 letters;
• Visual loss should be mainly due to the presence of any eligible types of ME.

Exclusion Criteria:

• Women of child-bearing potential,
• Active malignancies;
• History of stroke less than 6 months prior to screening;
• Uncontrolled systemic inflammation or infection, related directly to the underlying causal disease of ME;
• Active diabetic retinopathy, active ocular/periocular infectious disease or active severe intra-ocular inflammation;
• Any type of advanced, severe or unstable ocular disease or its reatment;
• ME with a high likelihood of spontaneous resolution.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ranibizumab; A 0.5 mg ranibizumab intravitreal injection was given to the study eye at baseline, and then as needed based on evidence of disease activity.	Drug: Ranibizumab; Ranibizumab 0.5mg/0.5mL was administered intravitreally to the participant.
Sham Comparator: Sham control; Sham injection was given to the study eye at baseline, and then treatment was given based on evidence of disease activity. At month 1, if treatment was needed, sham was administered. At month 2, participants switched to open-label ranibizumab on an as needed basis.	Other: Sham control; The sham vial did not contain active drug (empty sterile vial). The sham injection was an imitation of an intravitreal injection using an injection syringe without a needle touching the eye.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Best-corrected Visual Acuity (BCVA) in Study Eye	BCVA was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity (VA) testing charts at an initial testing distance of 4 meters. A positive change from baseline indicated improvement.	Baseline, Month 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss	VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using ETDRS-like visual acuity testing charts at a testing distance of 4 meters.	Month 2, Month 6, Month 12
Change From Baseline in BCVA in Study Eye up to Month 2	BCVA was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity (VA) testing charts at an initial testing distance of 4 meters. A positive change from baseline indicated improvement.	Baseline, Month 1, Month 2
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye	CSFT wasassessed by optical coherence tomography (OCT). A negative change from baseline indicates improvement.	Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Change From Baseline in Central Subfield Volume (CSFV) in Study Eye	CSFV was assessed OCT. A negative change from baseline indicates improvement.	Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Number of Participants With Presence or Absence of Intra-retinal Fluid in Study Eye Compared to Baseline	The presence of intra-retinal fluid was assessed by OCT.	Month 2, Month 6, Month 12
Number of Participants With Presence or Absence of Subretinal Fluid in Study Eye Compared to Baseline	The presence of subretinal fluid was assessed by OCT.	Month 2, Month 6, Month 12
Number of Participants With Presence of Active Macular Edema (ME) Leakage	The presence of active ME leakage was assessed by fluorescein angiography (FA).	Month 2
Number of Participants Requiring Rescue Treatment at Month 1	Rescue treatment with laser photocoagulation or periocular treatment could be administered at Month 1 only if the participant had a visual acuity loss of > 5 letters due to disease activity from baseline to Month 1.	Month 1
Average Change From Baseline in BCVA	BCVA was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity (VA) testing charts at an initial testing distance of 4 meters. A positive change from baseline indicated improvement.	Baseline (BL), month 1 through month 6, month 1 through month 12
Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters	VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using ETDRS-like visual acuity testing charts at a testing distance of 4 meters.	Month 2, Month 6 , Month 12
Number of Participants With Ranibizumab Treatments	The number of participants administered study treatments, according to treatment frequency, was assessed.	Month 12
Number of Participants With Re-treatments	The number of participants, administered re-treatments according to treatment frequency, was assessed. Re-treatment was defined as an administration of study medication following at least one non-missed visit where treatment was not administered in the study eye. Up to Month 12, the maximum number of retreatments was 5.	Month 6, month 12
Number of Primary Reasons for Decision to Treat by Investigator	The total number of primary reasons for decisions to treat was assessed. A single participant could have had multiple primary reasons for treatment.	12 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: April 30, 2013
• First Submitted That Met QC Criteria: May 2, 2013
• First Posted (Estimate): May 3, 2013

Study Record Updates

• Last Update Posted (Estimate): May 23, 2016
• Last Update Submitted That Met QC Criteria: April 14, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Vision Impairment
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: CRFB002G2302; 2012-005418-20 (EudraCT Number)