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

April 16, 2012
April 11, 2016
May 2012
October 2014   (final data collection date for primary outcome measure)
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
Collection of all ocular and non-ocular adverse events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Safety assessments will consist of monitoring and recording of all adverse events (AEs) and serious adverse events (SAEs), ophthalmic examinations, evaluation of cataract formation, intraocular pressure by tonometry, vital signs, and routine laboratory parameters.
Complete list of historical versions of study NCT01580020 on ClinicalTrials.gov Archive Site
  • 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
  • Collection of ocular and non-ocular adverse events of both treatment arms [ Time Frame: 15 months ] [ Designated as safety issue: No ]
    • To describe and compare the ocular and non-ocular adverse events over a cumulative 15-months period - including the core and extension study - in patients treated with Lucentis vs. Ozurdex
  • Mean average change of best corrected visual acuity [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    • To compare the mean average change of the best-corrected visual acuity (BCVA) assessed by ETDRS chart over the 6-months study period in patients treated with Lucentis vs. Ozurdex
  • Mean average change of best corrected visual acuity [ Time Frame: 12 month ] [ Designated as safety issue: No ]
    + To compare the mean average change of the best-corrected visual acuity (BCVA) assessed by ETDRS chart over 12-months study period- including the core and the extension study in patients treated with Lucentisvs. Ozurdex
  • Mean change in central subfield thickness [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    • To compare the mean change in central subfield thickness (CSFT) as assessed by OCT over the 6-months study period in patients treated with Lucentis vs. Ozurdex
  • Mean change in central subfield thickness [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    • To compare the mean change in central subfield thickness (CSFT) as assessed by OCT over the 12-months study period in patients treated with Lucentis vs. Ozurdex
  • Change of patients´ Quality of Life [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    • To compare changes in the quality of life according to NEI-VFQ 25, SF36 and EQ-5D questionnaires under treatment of ranibizumab versus Ozurdex® from Baseline to Month 6
  • Time to the first retreatment and the total number of treatments of both treatment arms [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    • To evaluate the time to the first retreatment and the total number of treatments for both Lucentis PRN and Ozurdex
Not Provided
Not Provided
 
Extension Study to Compare Long-term Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With RVO
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)
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).
Not Provided
Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Retinal Vein Occlusion
  • 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.
  • 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
  • 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

    Intervention: Biological: RFB002
  • 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.
    Intervention: Drug: Dexamethasone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
175
October 2014
October 2014   (final data collection date for primary outcome measure)

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)
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT01580020
CRFB002EDE20, 2011-005045-13
No
Not Provided
Not Provided
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP