A Study of the Efficacy and Safety of Ranibizumab Injection in Patients With Macular Edema Secondary to Branch Retinal Vein Occlusion (BRAVO)

Macular Edema Clinical Trial

— BRAVO  

Official title:

A Phase III, Multicenter, Randomized, Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab Injection Compared With Sham in Subjects With Macular Edema Secondary to Branch Retinal Vein Occlusion

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00486018
• Other study ID #: FVF4165g
• Status: Completed
• Phase: Phase 3
• First received: June 11, 2007
• Last updated: April 25, 2011
• Start date: July 2007
• Est. completion date: November 2009

Study information

• Verified date: April 2011
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This was a Phase III, multicenter, randomized, double-masked, sham injection-controlled study of the efficacy and safety of intravitreal ranibizumab compared with sham injections in patients with macular edema secondary to branch retinal vein occlusion (BRVO); 397 patients with BRVO were enrolled at 93 investigational sites in the United States. The study included a treatment period (6 months) and an observation period (6 months).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 397
• Est. completion date: November 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Willingness to provide signed Informed Consent Form

• Age = 18 years

• For sexually active women of childbearing potential, use of an appropriate form of contraception (or abstinence) for the duration of the study

• Ability and willingness to return for all scheduled visits and assessments

Ocular Inclusion Criterion (Study Eye):

• Foveal center-involved macular edema secondary to BRVO

• BCVA using ETDRS charts of 20/40 to 20/400 (Snellen equivalent)

• Mean central subfield thickness = 250 µm on two optical coherence tomography (OCT) measurements (at screening [confirmed by the central reading center] and Day 0 [confirmed by the evaluating physician])

• Media clarity, pupillary dilation, and participant cooperation sufficient to obtain adequate fundus photographs

Exclusion Criteria:

• History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0

• History of any anti-vascular endothelial growth factor (VEGF) treatment in fellow eye within 3 months prior to Day 0

• History of any systemic anti-VEGF or pro-VEGF treatment within 6 months prior to Day 0

• History of allergy to fluorescein

• History of allergy to ranibizumab injection or related molecule

• Relevant systemic disease that may be associated with increased systemic VEGF levels (namely, all active malignancies); history of successfully treated malignancies is not an exclusion criterion

• Uncontrolled blood pressure

• Pregnancy or lactation

• Any condition that, in the opinion of the investigator, would preclude participation in the study (e.g., chronic alcoholism or drug abuse, personality disorder or use of major tranquilizers, indicated difficulty in long-term follow-up, and likelihood of survival of less than 1 year)

• Participation in an investigational trial within 30 days prior to Day 0 that involved treatment with any drug (excluding vitamins and minerals) or device that has not received regulatory approval at time of study entry

Ocular Exclusion Criteria (Study Eye):

• Prior episode of retinal vein occlusion (RVO)

• Brisk afferent pupillary defect

• History of radial optic neurotomy or sheathotomy

• History or presence of age-related macular degeneration (AMD; dry or wet form)

• History of any anti-VEGF treatment in the study eye within 3 months prior to Day 0

• History of laser photocoagulation for macular edema within 4 months prior to Day 0

• History of panretinal scatter photocoagulation or sector laser photocoagulation within 3 months prior to randomization or anticipated within the next 4 months following randomization

• History of intraocular corticosteroid use within 3 months prior to Day 0

• History of pars plana vitrectomy

• History of intraocular surgery (including cataract extraction, scleral buckle, etc.) within 2 months prior to Day 0 or anticipated within the next 7 months following Day 0

• History of yttrium-aluminum-garnet capsulotomy performed within 2 months prior to Day 0

• Previous filtration surgery in the study eye

• History of herpetic ocular infection

• History of ocular toxoplasmosis

• History of rhegmatogenous retinal detachment

• History of idiopathic central serous chorioretinopathy

• Evidence upon examination of vitreoretinal interface disease (e.g., vitreomacular traction, epiretinal membrane), either on clinical examination or OCT, thought to be contributing to macular edema

• An eye that, in the investigator's opinion, would not benefit from resolution of macular edema, such as eyes with foveal atrophy, dense pigmentary changes, or dense subfoveal hard exudates

• Presence of an ocular condition that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the study (e.g., uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass syndrome, or prior macula-off rhegmatogenous retinal detachment)

• Visually significant hemorrhage obscuring the fovea and felt to be a major contributor to reduced visual acuity

• Presence of a substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., a 20/40 cataract)

• Aphakia

• Relevant ocular disease that may be associated with increased intraocular VEGF levels (namely, uveitis, neovascular glaucoma, neovascular AMD, diabetic retinopathy, diabetic maculopathy, or ocular ischemic syndrome)

• Improvement of > 10 letters on best corrected visual acuity (BCVA) between screening and Day 0

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Edema
• Macular Edema
• Retinal Vein Occlusion

Intervention

Drug:
• Ranibizumab injection 0.3 mg
Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
• Ranibizumab injection 0.5 mg
Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
• Sham injection
Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at 6 Months	BCVA score in the study eye was based on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts (number of correct letters) and assessed at a starting distance of 4 meters.	Baseline and 6 months	No
Secondary	Percentage of Participants Who Gained = 15 Letters in BCVA Score at Month 6 Compared With Baseline	BCVA score based on the ETDRS visual acuity charts (number of correct letters) and assessed at a starting distance of 4 meters.	Baseline and 6 months	No
Secondary	Percentage of Participants Who Lost < 15 Letters in BCVA Score at Month 6 Compared With Baseline	BCVA score based on the ETDRS visual acuity charts (number of correct letters) and assessed at a starting distance of 4 meters. The percentage of subjects who lost <15 letters will be greater than the percentage of subjects who "gained >=15 letters" as "losing <15 letters" includes both those who gained >=15 letters and those who were "stable" (i.e. lost between 1 and 14 letters, had no change, or gained between 1 and 14 letters).	Baseline and 6 months	No
Secondary	Percentage of Participants With a Central Foveal Thickness of = 250 µm at Month 6	A central reading center assessed all optical coherence tomography (OCT) images. Central foveal thickness was defined as the center point thickness.	6 months	No
Secondary	Mean Absolute Change From Baseline in Central Foveal Thickness at Month 6	A central reading center assessed all OCT images. Central foveal thickness was defined as the center point thickness.	Baseline and 6 months	No
Secondary	Mean Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Near Activities Subscale Score at Month 6	The NEI VFQ-25 (v. 2000; Interviewer Format) consisted of the base set of 25 questions, plus the optional additional questions (where questions A3, A4, and A5 pertained to the Near Activities Subscale). Scores ranged from 0 to 100; a higher score represented better functioning.	Baseline and 6 months	No
Secondary	Mean Change From Baseline in the NEI VFQ-25 Distance Activities Subscale Score at Month 6	The NEI VFQ-25 (v. 2000; Interviewer Format) consisted of the base set of 25 questions, plus the optional additional questions (where questions A6, A7, and A8 pertained to the Distance Activities Subscale). Scores ranged from 0 to 100; a higher score represented better functioning.	Baseline and 6 months	No