Assess the Efficacy/Safety of Intravitreal Ranibizumab in Patients With Vision Loss Due to Choroidal Neovascularization.

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

This study was conducted to evaluate the efficacy and safety of 0.5 mg ranibizumab in adult and adolescent patients with visual impairment due to choridal neovascularization (CNV).

Study Overview

• Status: Completed
• Conditions: Choroidal Neovascularization (CNV)
• Intervention / Treatment: Drug: Ranibizumab; Other: Sham control

• Study Type: Interventional
• Enrollment (Actual): 183
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2000
      • Novartis Investigative Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Novartis Investigative Site
  • Tasmania
    • South Launceston, Tasmania, Australia, 7249
      • Novartis Investigative Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Novartis Investigative Site
• Czech Republic
  • Hradec Kralove, Czech Republic, 505 05
    • Novartis Investigative Site
  • Praha 10, Czech Republic, 100 34
    • Novartis Investigative Site
• Denmark
  • Glostrup, Denmark, 2600
    • Novartis Investigative Site
• France
  • Paris cedex 10, France, 75010
    • Novartis Investigative Site
  • Paris, Cedex 12, France, F-75571
    • Novartis Investigative Site
• Germany
  • Bochum, Germany, 44892
    • Novartis Investigative Site
  • Bonn, Germany, 53127
    • Novartis Investigative Site
  • Duesseldorf, Germany, 40225
    • Novartis Investigative Site
  • Freiburg i. Br, Germany, 79106
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Muenster, Germany, 48149
    • Novartis Investigative Site
  • Muenster, Germany, 48145
    • Novartis Investigative Site
  • Regensburg, Germany, 93042
    • Novartis Investigative Site
  • Tübingen, Germany, 72076
    • Novartis Investigative Site
• Greece
  • Patras, Greece, 265 00
    • Novartis Investigative Site
  • Thessaloniki, Greece, GR 56429
    • Novartis Investigative Site
  • GR
    • Heraklion Crete, GR, Greece, 711 10
      • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1083
    • Novartis Investigative Site
  • Budapest, Hungary, 1133
    • Novartis Investigative Site
  • Debrecen, Hungary, 4012
    • Novartis Investigative Site
  • Debrecen, Hungary, 4043
    • Novartis Investigative Site
  • Szeged, Hungary, H-6720
    • Novartis Investigative Site
• Italy
  • BA
    • Bari, BA, Italy, 70124
      • Novartis Investigative Site
  • CT
    • Catania, CT, Italy, 95123
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20132
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00198
      • Novartis Investigative Site
  • UD
    • Udine, UD, Italy, 33100
      • Novartis Investigative Site
  • VA
    • Varese, VA, Italy, 21100
      • 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, 06591
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 03080
      • Novartis Investigative Site
• Latvia
  • Riga, Latvia, 1002
    • Novartis Investigative Site
• Lithuania
  • Vilnius, Lithuania, LT-08661
    • Novartis Investigative Site
  • LTU
    • Kaunas, LTU, Lithuania, 50009
      • Novartis Investigative Site
• Peru
  • Lima
    • San Isidro, Lima, Peru, 27
      • Novartis Investigative Site
• Poland
  • Katowice, Poland, 40-594
    • Novartis Investigative Site
  • Wroclaw, Poland, 50-556
    • Novartis Investigative Site
• Portugal
  • Coimbra, Portugal, 3000-354
    • Novartis Investigative Site
  • Porto, Portugal, 4200-319
    • 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
  • 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
  • Lausanne, Switzerland, 1007
    • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Istanbul, Turkey, 34420
    • Novartis Investigative Site
  • Kocaeli, Turkey, 41380
    • 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

Key Inclusion Criteria:

• Diagnosis of active CNV secondary to any causes with the CNV or its sequelae affecting the fovea;
• BCVA must be between ≥ 24 and ≤ 83 letters in the study eye;
• Visual loss in the study eye should mainly be due to the presence of any eligible types of CNV;

Key Exclusion Criteria:

• Women of child-bearing potential;
• Active malignancies;
• History of stroke less than 6 months prior to screening;
• Uncontrolled systemic inflammation or infection;
• Active diabetic retinopathy, active ocular/periocular infectious disease or active severe intra-ocular inflammation;
• CNV- conditions with a high likelihood of spontaneous resolution;
• History of intravitreal treatment with steroids;
• History of laser photocoagulation;
• History of intraocular treatment with any anti-angiogenic drugs.

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 could switch 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 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. The data were analyzed using mixed model repeated measures (MMRM) which contained scheduled visit, the type of underlying pathophysiologic mechanism (angloid streaks versus others) and treatment group as fixed effect factors, centered baseline BCVA as a continuous covariate and treatment group by visit and visit by centered baseline BCVA interactions. A positive change from baseline indicated improvement.	Baseline, Month 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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. The data were analyzed using analysis of covariance (ANCOVA) model which contained the type of underlying pathophysiologic mechanism (angloid streaks versus others) and treatment group as fixed effect factors, centered baseline BCVA as a continuous covariate. A positive change from baseline indicated improvement.	Baseline, Month 1, Month 2
Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye	CSFT was assessed 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.	Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Number of Participants With Presence of Intra-retinal Fluid in Study Eye Compared to Baseline	The presence of intra-retinal fluid was assessed by OCT.	Baseline, Month 2, Month 6, Month 12
Number of Participants With Presence of Subretinal Fluid in Study Eye Compared to Baseline	Presence of subretinal fluid in study eye compared to baseline	Baseline, Month 2, Month 6, Month 12
Number of Participants With Presence of Active Chorioretinal Leakage	The presence of active chorioretinal leakage was assessed by photography imaging, i.e. fluorescein angiography (FA).	Baseline, Month 2, Month 6, Month 12
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. BCVA was assessed at each month from Month 1 through Month 6 or at each month from Month 1 through month 12, and the data were averaged. The outcome measure is reporting the change between baseline and average BCVA from Month 1 through Month 6 or from Month 1 through Month 12 (average BCVA - baseline BCVA). 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 > 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
Number of Participants With Requirement for 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
Number of Participants With Ranibizumab Treatments in Study Eye	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 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.	Month 12

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: April 23, 2013
• First Submitted That Met QC Criteria: April 23, 2013
• First Posted (Estimate): April 25, 2013

Study Record Updates

• Last Update Posted (Estimate): August 26, 2016
• Last Update Submitted That Met QC Criteria: August 15, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Vision Impairment; Abnormal growth of blood vessels
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Uveal Diseases; Choroid Diseases; Metaplasia; Choroidal Neovascularization; Neovascularization, Pathologic; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: CRFB002G2301; 2012-005417-38 (EudraCT Number)