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

NCT02953938 | Completed Phase 4 Results

• 1 other identifier: CRFB002EJP09
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 7

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  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

  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

  Month 1 through Month 12

Study Arms (2)

mono therapy

ACTIVE COMPARATOR

ranibizumab alone

Biological: Ranibizumab

combination therapy

EXPERIMENTAL

ranibizumab with Grid\&Direct short pulse laser photocoagulation

Biological: Ranibizumab; Radiation: Grid&Direct short pulse laser photocoagulation

Interventions

Ranibizumab BIOLOGICAL

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

Also known as: RFB002E

combination therapy; mono therapy

Grid&Direct short pulse laser photocoagulation RADIATION

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

combination therapy

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

Novartis Investigative Site

Nagakute, Aichi-ken, 480-1195, Japan

Location

Novartis Investigative Site

Fukuoka, Fukuoka, 812-8582, Japan

Location

Novartis Investigative Site

Kita-gun, Kagawa-ken, 761-0793, Japan

Location

Novartis Investigative Site

Tsu, Mie-ken, 514-8507, Japan

Location

Novartis Investigative Site

Matsumoto, Nagano, 390-8621, Japan

Location

Novartis Investigative Site

Mitaka, Tokyo, 181-8611, Japan

Location

Novartis Investigative Site

Hokkaido, 078-8510, Japan

Location

MeSH Terms

Conditions

Macular Edema; Retinal Vein Occlusion

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+1 (862) 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase IV, randomized, open-label, active-controlled, 2-arm, multicenter study

Study Record Dates

• First Submitted: November 1, 2016
• First Posted: November 3, 2016
• Study Start: December 15, 2016
• Primary Completion: December 28, 2018
• Study Completion: December 28, 2018
• Last Updated: February 25, 2020
• Results First Posted: February 25, 2020

Record last verified: 2020-02

Locations

JP (7)