Extension Study to Compare Long-term Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With RVO

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01580020
First received: April 16, 2012
Last updated: April 11, 2016
Last verified: April 2016
  Purpose
The study is intended to characterize the clinical benefit regarding safety and efficacy of a long term treatment with Lucentis in comparison with Ozurdex over an additional 6 months and a 3-month follow-up period, following the initial 6-month treatment in the respective core studies CRFB002EDE17 (NCT01396057) and CRFB002EDE18 (NCT01396083).

Condition Intervention Phase
Retinal Vein Occlusion
Biological: RFB002
Drug: Dexamethasone
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Multi-center, 6-month Extension Study Comparing the Long-term Efficacy and Safety of Lucentis (Ranibizumab) Intravitreal Injections Versus Ozurdex (Dexamethasone) Intravitreal Implant in Patients With Visual Impairment Due to Macular Edema Following Branch Retinal Vein Occlusion (BRVO) or Central Retinal Vein Occlusion (CRVO) Who Have Completed the Respective Core Study (CRFB002EDE17 or CRFB002EDE18)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    The number of participants who experienced Adverse events, serious AE and death


Secondary Outcome Measures:
  • Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group [ Time Frame: Baseline, 6 months and 12 months ] [ Designated as safety issue: No ]
    Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. The range of BCVA (EDTRS) is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement

  • Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline [ Time Frame: 12 month ] [ Designated as safety issue: No ]
    BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. An increased score indicates improvement in acuity. This outcome assessed the percentage of participants who were gaining/losing ≥15, 10 or 5 more letters of visual acuity at month 12 as compared with baseline

  • Change in Central Subfield Thickness (CSRT) From Baseline to Month 12 [ Time Frame: Baseline , Month 12 ] [ Designated as safety issue: No ]
    High Resolution OCT was performed at every study visit by Spectral Domain OCT (if not available Time Domain OCT was acceptable) and the images were transferred to a digital video disc. These assessments were performed by trained and adequately qualified experts at the sites and prior to any study drug administration. CSFT is the average retinal thickness of the circular area with 1 mm diameter around the foveal center.

  • Change of Foveal Center Point Thickness (FCPT) From Baseline to Month 12 [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: No ]
    FCPT (foveal center point thickness) was assessed by central reading center to ensure error- corrected measurements of retinal thickness and volumes,

  • Change in Mean Visual Function Questionnaire (VFQ-25) [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
    The VFQ-25 composite and subscale scores range from 0 to 100, a higher score indicating better functioning. The 12 subscales in the VFQ-25 are general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. The scores on the subscales were added together for a total score, which ranged from 0 to 100. A higher score indicated improvement in quality of life due to vision function.

  • Change in SF-36 Summary Scores [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: No ]
    The SF-36 measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score. Scores for each subscale range from 0 to 10, and the composite scores range from 0 to 100, with higher scores indicating better health. A positive change from Baseline score indicates improvement in quality of life.

  • Change in Euro Quality of Life Questionnaire (EQ-5D) VAS Summary Scores [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: No ]
    The Euro Quality of Life Questionnaire (EQ-5D) standardized instrument was utilized to measure health outcomes related to mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Participants self-rate their health on a visual, vertical analogue scale from 0 to 100 where the endpoints are labeled "Best imaginable health state" (100) and "worst imaginable health state" (0).

  • Time to the First Retreatment of Both Treatment Arms [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Time to the first retreatment


Enrollment: 175
Study Start Date: May 2012
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ranibizumab (Arm A)

The PRN injection scheme applied in the core study will also be followed during this extension study:

Patients should be monitored monthly (starting at V1E) for VA and treatment is to be resumed when monitoring indicates loss of VA due to disease activity. Monthly injections should then be administered until stable VA is reached again for 3 consecutive monthly assessments (implying a minimum of 2 injections during stable VA). The interval between 2 doses should not be shorter than 1 month

Biological: RFB002
0.5 mg/0.05 mL solution to be injected intravitreally. Ranibizumab was formulated as a sterile solution aseptically filled in a sterile glass vial. Each vial contained ranibizumab in an aqueous solution (pH 5.5) with histidine, trehalose and polysorbate 20.
Sham Comparator: Dexamethasone (Arm B)
A PRN re-treatment scheme will be applied for the Ozurdex arm during this extension study, i.e. patients may receive an implant at V1E or later as needed: Patients should be monitored monthly and if there is a decline from stable VA stability due to macular edema patients will receive another intravitreal implant. (700 µg; long acting release (LAR)) given that in the opinion of the investigator the patient would benefit from the re-treatment. However, a minimum period of 5 months in between implantations is required.
Drug: Dexamethasone
Ozurdex (Dexamethasone): intravitreal implant as per commercial label (700 µg Dexamethasone; Dexamethasone was formulated as a rod shaped implant to be inserted into the eye by an applicator. The implant as well as the respective applicator were suitable for single use only. Dexamethasone had to be stored according to label instructions and it had to be kept in a secure locked facility

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have completed the core study assessments at month 6 of study CRFB002EDE17 or CRFB002EDE18, respectively

Exclusion Criteria:

  • Patients who experienced an uncontrollable rise in IOP during the core study CRFB002EDE17 respectively CRFB002EDE18, i.e. IOP could not be decreased to a stable level of < 25mmHg.
  • Use of other investigational drugs
  • Current use or likely need of systemic medications known to be toxic to the lens, retina or optic nerve
  • History of hypersensitivity to Ranibizumab or Ozurdex or any component of the ranibizumab respectively Ozurdey formulation
  • Any type of advanced, severe or unstable disease or its treatment, that could interfere with evaluations or put the patient at special risk
  • Women
  • who were pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (>5 mIU/mL)
  • who were menstruating and capable of becoming pregnant* and not practicing a medically approved method of contraception (Pearl Index <1**)*** during and up to at least 4 weeks after the end of treatment. A negative pregnancy test (serum) for all women and for girls entering menarche was required with sufficient lead time before randomization

    • definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/mL or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy

      • examples of particularly reliable methods with Pearl Index (PI) <1, according to guidelines of "Deutsche Gesellschaft für Gynäkologie und Geburtshilfe":

        • Combination pill with estrogen and gestagen (no mini-pill, PI=0.1-0.9)
        • Vaginal ring (NuvaRing®, PI=0.65 uncorr.; 0.4 corr.)
        • Contraceptive patch (EVRA®, PI= 0.72 uncorr.; 0.9 corr.)
        • Estrogen-free ovulation inhibitors (Cerazette®, PI=0.14)
        • Progestin-containing contraceptives (Implanon®, PI=0-0.08)
        • Injectable 3-month depot progestins (PI=0.3-1.4; 0.88 corr.)
        • Intra-uterine progestin device (Mirena®, PI=0.16)
  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: NCT01580020

Locations
Germany
Novartis Investigative Site
Augsburg, Germany, 85155
Novartis Investigative Site
Bad Rothenfelde, Germany, 49214
Novartis Investigative Site
Berlin, Germany, 10713
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Bonn, Germany, 53127
Novartis Investigative Site
Bremen, Germany, 28209
Novartis Investigative Site
Chemnitz, Germany, 09113
Novartis Investigative Site
Darmstadt, Germany, 64297
Novartis Investigative Site
Dresden, Germany, 01307
Novartis Investigative Site
Duesseldorf, Germany, 40225
Novartis Investigative Site
Düsseldorf, Germany, 40212
Novartis Investigative Site
Frankfurt, Germany, 60318
Novartis Investigative Site
Freiburg i. Br, Germany, 79106
Novartis Investigative Site
Glauchau, Germany, 08371
Novartis Investigative Site
Göttingen, Germany, 37075
Novartis Investigative Site
Halle, Germany, 06114
Novartis Investigative Site
Hamburg, Germany, 20246
Novartis Investigative Site
Ingolstadt, Germany, 85049
Novartis Investigative Site
Karlsruhe, Germany, 76133
Novartis Investigative Site
Karlsruhe, Germany, 76199
Novartis Investigative Site
Koeln, Germany, 50935
Novartis Investigative Site
Leipzig, Germany, 04103
Novartis Investigative Site
Ludwigshafen, Germany, 67063
Novartis Investigative Site
Marburg, Germany, 35039
Novartis Investigative Site
Minden, Germany, 32427
Novartis Investigative Site
Muelheim, Germany, 45468
Novartis Investigative Site
Muenster, Germany, 48145
Novartis Investigative Site
Muenster, Germany, 48149
Novartis Investigative Site
München, Germany, 80336
Novartis Investigative Site
München, Germany, 81675
Novartis Investigative Site
Recklinghausen, Germany, 45657
Novartis Investigative Site
Regensburg, Germany, 93042
Novartis Investigative Site
Sulzbach, Germany, 66280
Novartis Investigative Site
Tübingen, Germany, 72076
Novartis Investigative Site
Ulm, Germany, 89075
Novartis Investigative Site
Wolfsburg, Germany, 38442
Novartis Investigative Site
Wuerzburg, Germany, 97080
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01580020     History of Changes
Other Study ID Numbers: CRFB002EDE20  2011-005045-13 
Study First Received: April 16, 2012
Results First Received: September 28, 2015
Last Updated: April 11, 2016
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Novartis:
Macular Degeneration
Macular Edema
Retinal Vein Occlusion
Choroidal Neovascularization
Signs and Symptoms
Retinal Degeneration
Retinal Diseases
Eye Diseases
Venous Thrombosis Sensation Disorders
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Vision, Low
Signs
Vision Disorders

Additional relevant MeSH terms:
Retinal Vein Occlusion
Retinal Diseases
Eye Diseases
Venous Thrombosis
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Ranibizumab
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on August 25, 2016