Clinical trial NCT02953938: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Macular Edema Secondary to Branch Retinal Vein Occlusion (BRVO)
Keywords: Ranibizumab
Grid&Direct short pulse laser photocoagulation
Macular edema
Branch retinal vein occlusion
BRVO
BCVA
CSFT
pro re nata
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-11-03
Enrollment: 59
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase IV, randomized, open-label, active-controlled, 2-arm, multicenter study
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Difference in Mean Number of Ranibizumab Injections
timeFrame: Month 1 through Month 12
Secondary outcomes:
measure: The Mean Change in Best Corrected Visual Acuity (BCVA) Using Decimal Chart and Early Treatment Diabetic Retinopathy Study (ETDRS) Compared to Baseline
timeFrame: Month 1 through Month 12 (for ETDRS: Month 6 and Month 12)
measure: The Mean Change in BCVA From Month 1 Through Month 12 Compared to Baseline (Day 1) by the Treatment Arms
timeFrame: Month 1 through Month 12
measure: 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
timeFrame: Month 6 and Month 12
measure: 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
timeFrame: Month 1 through Month 12
Other outcomes:
Locations:
city: Nagakute-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Kita-gun
country: Japan
facility: Novartis Investigative Site
state: Kagawa
city: Tsu-city
country: Japan
facility: Novartis Investigative Site
state: Mie
city: Matsumoto-city
country: Japan
facility: Novartis Investigative Site
state: Nagano
city: Mitaka-city
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Hokkaido
country: Japan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: