Macular Edema Secondary to Branch Retinal Vein Occlusion (BRVO)Phase 4ZIPANGUNCT02953938
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
A Phase 4 study testing Ranibizumab and Grid&Direct short pulse laser photocoagulation in people with Macular Edema Secondary to Branch Retinal Vein Occlusion (BRVO), run by Novartis Pharmaceuticals at 7 sites in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Macular Edema Secondary to Branch Retinal Vein Occlusion (BRVO)
- What is being tested?
- Ranibizumab and Grid&Direct short pulse laser photocoagulation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 7 sitesJapan
- Study dates
- 15 Dec 2016to 28 Dec 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Japan7 sites
Novartis Investigative Site
Fukuoka, Fukuoka, 812-8582
Novartis Investigative Site
Hokkaido, 078-8510
Novartis Investigative Site
Kita-gun, Kagawa-ken, 761-0793
Novartis Investigative Site
Matsumoto, Nagano, 390-8621
Novartis Investigative Site
Mitaka, Tokyo, 181-8611
Novartis Investigative Site
Nagakute, Aichi-ken, 480-1195
Novartis Investigative Site
Tsu, Mie-ken, 514-8507
About this study
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)
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.
- Being tested
- Ranibizumab, Grid&Direct short pulse laser photocoagulation
- Keywords
- Ranibizumab, Grid&Direct short pulse laser photocoagulation, Macular edema, Branch retinal vein occlusion, BRVO, BCVA, CSFT, pro re nata
- Medical subject headings
- Macular Edema, Retinal Vein Occlusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanibizumabBiological
Also called RFB002E
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
Grid&Direct short pulse laser photocoagulationRadiation
Grid\&Direct short pulse laser photocoagulation is a kind of laser treatment to retina within vascular arcades and used to suppress macular edema
| Study group | Role | What they receive |
|---|---|---|
| mono therapy | Active comparator | ranibizumab alone Receives: Biological: Ranibizumab |
| combination therapy | Experimental | ranibizumab with Grid\&Direct short pulse laser photocoagulation Receives: Biological: Ranibizumab; Radiation: Grid&Direct short pulse laser photocoagulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Mean Number of Ranibizumab Injections
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.
Measured: Month 1 through Month 12
Secondary outcomes (4)
The Mean Change in Best Corrected Visual Acuity (BCVA) Using Decimal Chart and Early Treatment Diabetic Retinopathy Study (ETDRS) Compared to Baseline
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.
Measured: Month 1 through Month 12 (for ETDRS: Month 6 and Month 12)
The Mean Change in BCVA From Month 1 Through Month 12 Compared to Baseline (Day 1) by the Treatment Arms
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
Measured: Month 1 through Month 12
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
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
Measured: Month 6 and Month 12
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
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
Measured: Month 1 through Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2016 (estimated)
- Study start15 Dec 2016
- Primary completion28 Dec 2018
- Study completion28 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Macular Edema Secondary to Branch Retinal Vein Occlusion (BRVO)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase IV, randomized, open-label, active-controlled, 2-arm, multicenter study
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02953938
- Sponsor's protocol ID
- CRFB002EJP09
- Acronym
- ZIPANGU
- Status last verified
- Feb 2020
- First submitted
- 1 Nov 2016
- Last updated
- 25 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02953938
- Acronym / sponsor ID
- ZIPANGU / CRFB002EJP09
- Keywords
- Ranibizumab, Grid&Direct short pulse laser photocoagulation, Macular edema, Branch retinal vein occlusion, BRVO, BCVA, CSFT, pro re nata
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 15 Dec 2016 (actual)
- Primary completion
- 28 Dec 2018 (actual)
- Study completion
- 28 Dec 2018 (actual)
- First posted
- 3 Nov 2016 (estimated)
- Results
- Posted 25 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase IV, randomized, open-label, active-controlled, 2-arm, multicenter study
| Arm | Type | Receives |
|---|---|---|
| mono therapy | Active comparator | Biological: Ranibizumabranibizumab alone |
| combination therapy | Experimental | Biological: Ranibizumab, Radiation: Grid&Direct short pulse laser photocoagulationranibizumab with Grid\&Direct short pulse laser photocoagulation |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RanibizumabAlso: RFB002ERanibizumab 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 | Biological | combination therapy, mono therapy |
| Grid&Direct short pulse laser photocoagulationGrid\&Direct short pulse laser photocoagulation is a kind of laser treatment to retina within vascular arcades and used to suppress macular edema | Radiation | combination therapy |
Primary outcome
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.
4 secondary outcomes
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)
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided. 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
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ranibizumab and Grid&Direct short pulse laser photocoagulation in people with Macular Edema Secondary to Branch Retinal Vein Occlusion (BRVO), run by Novartis Pharmaceuticals at 7 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in Mean Number of Ranibizumab Injections (time frame: Month 1 through Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2020.