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Study to Show a Superior Benefit in Terms of Reduction of Ranibizumab Injections in Patients Receiving Ranibizumab Plus Laser Photocoagulation Combination Therapy Without Loss of Efficacy and Safety (ZIPANGU)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02953938
Recruitment Status : Completed
First Posted : November 3, 2016
Results First Posted : February 25, 2020
Last Update Posted : February 25, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This is a Phase IV, randomized, open-label, active-controlled, 2-arm, multicenter study. The primary objective was assessed by the difference in the mean number of ranibizumab injections applied up to Month 11 between the 2 treatment arms. Patients were randomized in a 1:1 ratio to 1 of the 2 treatment arms; i.e. Arm 1 ranibizumab monotherapy, Arm 2 ranibizumab with Grid&Direct short pulse laser photocoagulation combination therapy. There were 3 periods in this study: Screening Period (visit 1), Treatment Period (visit 2 to Visit 13) and Follow-up Period (visit 14). In addition to screening and Baseline (visit 2), there were monthly visits from Month 1 to Month 12. This study included male and female patients (≥20 years old) diagnosed with visual impairment due to ME secondary to BRVO.

Condition or disease Intervention/treatment Phase
Macular Edema Secondary to Branch Retinal Vein Occlusion (BRVO) Biological: Ranibizumab Radiation: Grid&Direct short pulse laser photocoagulation Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Phase IV, randomized, open-label, active-controlled, 2-arm, multicenter study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 12-month, Phase IV, Open-label, Randomized, Active Controlled, 2-arm, Multicenter Study Assessing the Efficacy and Safety of Intravitreal Ranibizumab Combined With Grid&Direct Short Pulse Laser Photocoagulation Versus a PRN Ranibizumab Monotherapy in Japanese Patients With Macular Edema Secondary to Branch Retinal Vein Occlusion (BRVO)
Actual Study Start Date : December 15, 2016
Actual Primary Completion Date : December 28, 2018
Actual Study Completion Date : December 28, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema
Drug Information available for: Ranibizumab

Arm Intervention/treatment
Active Comparator: mono therapy
ranibizumab alone
Biological: Ranibizumab

Ranibizumab is a biologic and known anti-VEGF (vascular endothelial growth factor) medication approved for treatment of ME (Macular Edema) due to RVO (Retinal Vein occlusion)

0.5 mg ranibizumab applied one + PRN as intravitreal injection of 0.05 mL, with or without laser treatment

Other Name: RFB002E

Experimental: combination therapy
ranibizumab with Grid&Direct short pulse laser photocoagulation
Biological: Ranibizumab

Ranibizumab is a biologic and known anti-VEGF (vascular endothelial growth factor) medication approved for treatment of ME (Macular Edema) due to RVO (Retinal Vein occlusion)

0.5 mg ranibizumab applied one + PRN as intravitreal injection of 0.05 mL, with or without laser treatment

Other Name: RFB002E

Radiation: Grid&Direct short pulse laser photocoagulation
Grid&Direct short pulse laser photocoagulation is a kind of laser treatment to retina within vascular arcades and used to suppress macular edema




Primary Outcome Measures :
  1. Difference in Mean Number of Ranibizumab Injections [ Time Frame: Month 1 through Month 12 ]

    Number of ranibizumab treatments from Day 1 to Month 11 using full analysis set (observed) based on a stratified Cochran-Mantel-Haenszel (CMH) test. Stratification was done based on categories of baseline decimal VA (<0.3, or =>0.3). Difference of mean number of injections, 95% confidence interval (CI) of difference and one-sided p-value of the CMH test was reported. Analysis was conducted within the FAS with observed data.

    Stratification was based on baseline visual acuity on logMAR scale (<0.52, >=0.52). Test was one-sided.



Secondary Outcome Measures :
  1. The Mean Change in Best Corrected Visual Acuity (BCVA) Using Decimal Chart and Early Treatment Diabetic Retinopathy Study (ETDRS) Compared to Baseline [ Time Frame: Month 1 through Month 12 (for ETDRS: Month 6 and Month 12) ]

    Summary of BCVA (letters) absolute value and change from Baseline at Month 12 in the study eye - full analysis set (LOCF) was based on an analysis of variance (ANOVA) model with treatment group, and stratification factors. Stratification was done based on categories of baseline decimal VA (<0.3, or =>0.3). The analyses was conducted within the FAS using the LOCF approach

    Stratification was based on baseline visual acuity on logMAR scale (<0.52, >=0.52). Test was one-sided.


  2. The Mean Change in BCVA From Month 1 Through Month 12 Compared to Baseline (Day 1) by the Treatment Arms [ Time Frame: Month 1 through Month 12 ]
    Summary of BCVA (logMAR) absolute value and change from Baseline at Month 12 in the study eye - full analysis set (LOCF) was based on an analysis of variance (ANOVA) model with treatment group, and stratification factors. Stratification was based on baseline visual acuity (< 0.52, >= 0.52). The analyses was conducted within the FAS using the LOCF approach

  3. BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye [ Time Frame: Month 6 and Month 12 ]

    Endpoints related to the number and proportion of patients with BCVA letter gain or loss from Baseline (Day1) was analyzed via stratified CMH test with stratification factors as described in primary model. The mean (SD) average (per patient) BCVA (logMAR) change from Baseline through Month 12

    Summary of BCVA (logMAR) mean average change from Baseline from Month 1 through Month 12 in the study eye


  4. The Mean Change in Change in Central Subfield Foveal Thickness (CSFT) From Month 1 Through Month 12 Compared to Baseline (Day1) by the Treatment Arms [ Time Frame: Month 1 through Month 12 ]
    The mean change in investigator-assessed CSFT from Month 1 through Month 12 was compared to Baseline (Day1) by the treatment arms. The analyses at each visit was based on an analysis of variance (ANOVA) model as analogous to BCVA. The analyses was conducted within the FAS using the Last-Observation-Carried-Forward (LOCF) approach



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of visual impairment exclusively due to ME secondary to BRVO
  • Best-corrected visual acuity score at Screening and Baseline (Day 1) between 0.5 and 0.05 decimal (i.e., between 73 and 19 letters in Early Treatment Diabetic Retinopathy Study (ETDRS) testing) with Landolt C charts inclusively (i.e., approximate logarithm of the minimum angle of resolution (logMAR) units of 0.3 to 1.30).
  • At Baseline (Day1), a maximum BCVA gain of 0.2 units logMAR conversion inclusively from screening is allowed as long as the BCVA score does not exceed the upper limit of 0.3 units logMAR.
  • Increased central subfoveal thickness (> 300 µm at Baseline (Day 1) when measured by SD-OCT)
  • Duration of vision deterioration ≤6 months (determined by self-report) at screening

Exclusion Criteria:

  • Pregnant or nursing (lactating) women
  • Stroke or myocardial infarction less than 3 months before Screening
  • Uncontrolled blood pressure defined as systolic value of >160 mm Hg or diastolic value of >100 mm Hg at Screening or Baseline (Day 1) Antihypertensive treatment can be initiated and must be taken for at least 30 days after which the patient can be assessed for study eligibility a second time
  • Any active periocular or ocular infection or inflammation (e.g., blepharitis, conjunctivitis, keratitis, scleritis, uveitis, endophthalmitis) at the time of Screening or Baseline (Day 1) in either eye
  • Uncontrolled glaucoma (intraocular pressure (IOP) ≥30 mm Hg on medication or according to investigator's judgment) at the time of Screening or Baseline (Day 1) or diagnosed within 6 months before Baseline (Day 1) in either eye
  • Neovascularization of the iris or neovascular glaucoma in the study eye
  • Use of any systemic anti-VEGF drugs within 6 months before Baseline (Day1) (e.g., sorafenib (Nexavar®), sunitinib (Sutent®), bevacizumab (Avastin®), ziv-aflibercept (ZALTRAP®))
  • Treatment (or anticipated treatment in the fellow eye for non-RVO indications during the study) with any anti-angiogenic drugs (including any anti-VEGF agents) within 3 months before Baseline (Day1) in fellow eye or before Baseline (Day 1) in the study eye (e.g., pegaptanib (Macugen®), ranibizumab (Lucentis®), bevacizumab (Avastin®), and aflibercept (EYLEA®))
  • Panretinal laser photocoagulation within 1 month before Baseline (Day1) or anticipated or scheduled within the next 12 months (Study periods) following Baseline (Day1) in the study eye
  • Any giving of focal or grid laser photocoagulation before Baseline (Day1) in the study eye
  • Use of intra- or periocular corticosteroids (including sub-Tenon) within 3 months before Screening in the study eye.
  • Any use of intraocular corticosteroid implants (e.g., dexamethasone (Ozurdex®), fluocinolone acetonide (Iluvien®)) in the study eye

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02953938


Locations
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Japan
Novartis Investigative Site
Nagakute-city, Aichi, Japan, 480-1195
Novartis Investigative Site
Fukuoka city, Fukuoka, Japan, 812-8582
Novartis Investigative Site
Kita-gun, Kagawa, Japan, 761-0793
Novartis Investigative Site
Tsu-city, Mie, Japan, 514-8507
Novartis Investigative Site
Matsumoto-city, Nagano, Japan, 390-8621
Novartis Investigative Site
Mitaka-city, Tokyo, Japan, 181-8611
Novartis Investigative Site
Hokkaido, Japan, 078-8510
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] January 21, 2018
Statistical Analysis Plan  [PDF] July 30, 2019

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02953938    
Other Study ID Numbers: CRFB002EJP09
First Posted: November 3, 2016    Key Record Dates
Results First Posted: February 25, 2020
Last Update Posted: February 25, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Ranibizumab
Grid&Direct short pulse laser photocoagulation
Macular edema
Branch retinal vein occlusion
BRVO
BCVA
CSFT
pro re nata
Additional relevant MeSH terms:
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Neoplasm Metastasis
Macular Edema
Retinal Vein Occlusion
Edema
Neoplastic Processes
Neoplasms
Pathologic Processes
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Venous Thrombosis
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Ranibizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents