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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01840410
First received: April 23, 2013
Last updated: August 15, 2016
Last verified: August 2016
  Purpose
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).

Condition Intervention Phase
Choroidal Neovascularization (CNV)
Drug: Ranibizumab
Other: Sham control
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in Best-corrected Visual Acuity (BCVA) in Study Eye to Month 2 [ Time Frame: Baseline, Month 2 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in BCVA in Study Eye up to Month 2 [ Time Frame: Baseline, Month 1, Month 2 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye [ Time Frame: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 ] [ Designated as safety issue: No ]
    CSFT was assessed by optical coherence tomography (OCT). A negative change from baseline indicates improvement.

  • Change From Baseline in Central Subfield Volume (CSFV) in Study Eye [ Time Frame: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 ] [ Designated as safety issue: No ]
    CSFV was assessed OCT. A negative change from baseline indicates improvement.

  • Number of Participants With Presence of Intra-retinal Fluid in Study Eye Compared to Baseline [ Time Frame: Baseline, Month 2, Month 6, Month 12 ] [ Designated as safety issue: No ]
    The presence of intra-retinal fluid was assessed by OCT.

  • Number of Participants With Presence of Subretinal Fluid in Study Eye Compared to Baseline [ Time Frame: Baseline, Month 2, Month 6, Month 12 ] [ Designated as safety issue: No ]
    Presence of subretinal fluid in study eye compared to baseline

  • Number of Participants With Presence of Active Chorioretinal Leakage [ Time Frame: Baseline, Month 2, Month 6, Month 12 ] [ Designated as safety issue: No ]
    The presence of active chorioretinal leakage was assessed by photography imaging, i.e. fluorescein angiography (FA).

  • Average Change From Baseline in BCVA [ Time Frame: Baseline (BL), Month 1 through Month 6, Month 1 through Month 12 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With ≥ 1, ≥ 5, ≥ 10 and ≥ 15 Letters Gain or Reaching 84 Letters [ Time Frame: Month 2, Month 6, Month 12 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With > 1, > 5, > 10 and > 15 Letters Loss [ Time Frame: Month 2, Month 6, Month 12 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Requirement for Rescue Treatment at Month 1 [ Time Frame: Month 1 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Ranibizumab Treatments in Study Eye [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    The number of participants administered study treatments, according to treatment frequency, was assessed.

  • Number of Participants With Re-treatments [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Primary Reasons for Decision to Treat by Investigator [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
    The total number of primary reasons for decisions to treat was assessed. A single participant could have had multiple primary reasons for treatment.


Enrollment: 183
Study Start Date: September 2013
Study Completion Date: November 2015
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01840410

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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01840410     History of Changes
Other Study ID Numbers: CRFB002G2301  2012-005417-38 
Study First Received: April 23, 2013
Results First Received: April 27, 2016
Last Updated: August 15, 2016
Health Authority: European Union: European Medicines Agency

Keywords provided by Novartis:
Vision Impairment
Abnormal growth of blood vessels

Additional relevant MeSH terms:
Neovascularization, Pathologic
Choroidal Neovascularization
Metaplasia
Pathologic Processes
Choroid Diseases
Uveal Diseases
Eye Diseases
Ranibizumab
Endothelial Growth Factors
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 29, 2016