LVO: Ranibizumab (Lucentis) for Macular Edema Secondary to Vein Occlusions

• Sponsor: Peter A Campochiaro, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT00407355
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 85
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Central and branch retinal vein occlusions are major causes of visual loss. Hemorrhage and capillary nonperfusion, when they involve the macula, can contribute to visual loss, but the major cause is macular edema. Focal and grid laser photocoagulation can sometimes provide benefit in patients with macular edema due to branch vein occlusions, but several laser treatments are often needed and recovery of vision can be very slow and incomplete 1. Laser photocoagulation does not provide benefit for macular edema due to central vein occlusions 2. Therefore, new treatments are needed.The objective of this study is to assess the bioactivity of 3 intravitreous injections 0.5 mg or 0.3 mg of ranibizumab in patients with macular edema due to central and branch retinal vein occlusions and correlate activity with peak and trough aqueous levels. The purpose of this research protocol is pilot study to determine if a randomized placebo controlled trial is warranted.

Condition or Disease	Intervention/Treatment	Phase
Macular Edema; Retinal Vein Occlusion	Drug: Intravitreal injection of ranibizumab .3 dose; Drug: Intravitreal injection of Ranibizumab .5 dose	Phase 1/Phase 2

Detailed Description

This study is a phase II, open-label study to investigate the bioactivity and pharmacodynamics of intravitreous ranibizumab in subjects with macular edema due to central and branch retinal vein occlusion. This pilot study will enroll 40 patients, 20 with central vein occlusion and 20 with branch vein occlusion. Each patient will receive three (3) injections of 0.5 or 0.3 mg of ranibizumab. The study consists of a 2-week screening period (Days -14 to -1), a 3-month treatment period, and a 9-month follow-up period. Consented subjects will enter the 14-day screening period to determine eligibility, including serum chemistry and hematology testing, urinalysis, pregnancy testing, and macular thickness based on optical coherence tomography measurements and fluorescein angiography. Patients who have reduction of visual acuity to 20/40 or worse due to foveal thickening from macular edema secondary to central or branch retinal vein occlusion and who meet eligibility criteria will be invited to enroll in the study. Baseline foveal thickness by OCT must be at least 250 um, which is often associated with VA of 20/40 or worse and provides sufficient thickening so that a treatment effect is easily detectable (Nguyen et al. 2004). Every effort will be made to recruit and enroll eligible patients from men and women of all ethnic and social backgrounds. It is expected that the 40 study subjects will be recruited over a 4-month period. Patients who meet entry criteria will be able to enroll in the study until the quota of patients has been achieved. All enrolled patients will receive either 0.5 or 0.3 mg injections of ranibizumab. Forty eligible subjects who have provided informed consent from one site (Wilmer Eye Institute at the Johns Hopkins Medical Institutions) will be enrolled, 20 with central vein occlusion and 20 with branch vein occlusion. In each of the 2 groups, 10 patients will be randomized to 0.5 mg of the ranibizumab, and 10 will be randomized to 0.3 mg of ranibizumab. Subjects will be identified and recruited through the clinic population of the Wilmer Eye Institute, including that of the Vitreoretinal Service and the Retinal Vascular Center, as well as through referral from physicians in the community. Announcement of the study will be made throughout the Wilmer Eye Institute, Johns Hopkins University School of Medicine through newsletters, pamphlets, and the clinical trials web site on the internet and intranet systems. Information about the study will also be sent to the community physicians as well as the ophthalmologists who often refer patients to the Wilmer Eye Institute. Every effort will be made to enroll eligible patients from men and women of all ethnic and social backgrounds.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot, Open-Label Study of the Safety, Tolerability, and Bioactivity of Multiple Intravitreal Injections of Ranibizumab in Subjects With Macular Edema Secondary to Vein Occlusions.
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: RBZ 0.3 RBZ at the 0.3 mg dose intravitreal injection	Drug: Intravitreal injection of ranibizumab .3 dose; PRN every 30 days withing retreatment criteria
Active Comparator: RBZ 0.5 RBZ dose level .5 for ITV injection	Drug: Intravitreal injection of Ranibizumab .5 dose; Intravitreal injection of Ranibizumab .5 dose every 30 days PRN with retreatment criteria

Outcome Measures

Primary Outcome Measures

1. Best Corrected Visual Acuity Change From Baseline at All Visits [continuous through 72 mos]

2. Retinal Thickness Change From Baseline at All Visits [continuous through 72 mos]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed informed consent and authorization of use and disclosure of protected health information

• Age greater than or equal to 18 years

• Diagnosis of macular edema due to central or branch retinal vein occlusion

• Foveal thickness of over 250 um, as assessed by OCT

• Best corrected visual acuity score in the study eye of 20/40 to 20/320 inclusive (Snellen equivalents using the ETDRS protocol at a distance of 4 meters). Only one eye will be treated in the study. If both eyes are eligible, the investigator will select the eye to be enrolled. Visual acuity score in the non-study eye must be greater than 25 letters (approximate Snellen equivalent 20/320).

• In the opinion of the investigator, decreased vision in the study eye is due to foveal thickening from vein occlusion and not from other obvious causes of decreased vision

• In the opinion of the investigator, laser photocoagulation can be withheld for at least 30 days after the patient has enrolled in the study

Exclusion Criteria:

• Prior/Concomitant Treatment

• Scatter laser photocoagulation or macular photocoagulation within 3 months of study entry in the study eye

• Use of intraocular or periocular injection of steroids in the study eye (e.g., triamcinolone) within 3 months of study entry

• Previous participation in a study and receipt of anti-angiogenic drugs (pegaptanib sodium [EYE001], ranibizumab, anecortave acetate, protein kinase C inhibitor, etc.) within 3 months of study entry Concurrent Ocular Conditions

• Vitreomacular traction or epiretinal membrane in the study eye evident biomicroscopically or by OCT

• Ocular inflammation (including 1+ or above in the amount of cells) in the study eye

• History of idiopathic or autoimmune uveitis in either eye

• Structural damage to the center of the macula in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), macular ischemia, or organized hard exudate plaque

• Ocular disorders in the study eye that may confound interpretation of study results, including diabetic retinopathy, retinal detachment, macular hole, or choroidal neovascularization of any cause (e.g., AMD, ocular histoplasmosis, or pathologic myopia)

• Concurrent disease in the study eye that could compromise visual acuity or require medical or surgical intervention during the study period

• Intraocular surgery in the study eye within 3 months of study entry

• During the study, if patients need to have cataract surgery, the patients will undergo the necessary cataract or any other surgery and will continued to be treated per protocol and followed.

• Uncontrolled glaucoma (defined as intraocular pressure greater than 30 mm Hg despite treatment with anti-glaucoma medication) or previous filtration surgery in the study eye

• Infectious blepharitis, keratitis, scleritis, or conjunctivitis (in either eye) or current treatment for serious systemic infection Systemic Conditions

• Blood pressure exceeding 160/95 (sitting) during the screening period

• Renal failure requiring dialysis or renal transplant

• Premenopausal women not using adequate contraception

• Previous participation in other studies of investigational drugs (excluding vitamins and minerals) within 3 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wilmer Eye Institute	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Peter A Campochiaro, MD
• Genentech, Inc.

Investigators

• Principal Investigator: Peter A Campochiaro, MD, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Peter A Campochiaro, MD, Principal Investigator, Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT00407355
• Other Study ID Numbers: 05-06-09-05
• First Posted: Dec 5, 2006
• Last Update Posted: Dec 4, 2013
• Last Verified: Oct 1, 2013

• Keywords provided by Peter A Campochiaro, MD, Principal Investigator, Johns Hopkins University: vein occlusion; macular edema
• Additional relevant MeSH terms: Macular Edema; Retinal Vein Occlusion; Edema; Ranibizumab

Study Results

Participant Flow

Recruitment Details	20 patients with central retinal vein occlusion(CRVO) and 20 patients with branch retinal vein occlusion (BRVO) were enrolled at the Wilmer Eye Institute

Arm/Group Title	CRVO	BRVO
Arm/Group Description	10 patients- RBZ dose level .5 for ITV injection given monthly for 3 months, then prn until 6 years 10 patients- RBZ dose level .3 for ITV injection given monthly for 3 months, then .5 prn until 6 years	10 patients- RBZ dose level .5 for ITV injection given monthly for 3 months, then prn until 6 years 10 patients- RBZ dose level .3 for ITV injection given monthly for 3 months, then .5 prn until 6 years
Period Title: Overall Study
STARTED	20	20
COMPLETED	10	9
NOT COMPLETED	10	11

Baseline Characteristics

Arm/Group Title	CRVO	BRVO	Total
Arm/Group Description	10 patients- RBZ dose level .5 for ITV injection given monthly for 3 months, then prn until 6 years 10 patients- RBZ dose level .3 for ITV injection given monthly for 3 months, then .5 prn until 6 years	10 patients- RBZ dose level .5 for ITV injection given monthly for 3 months, then prn until 6 years 10 patients- RBZ dose level .3 for ITV injection given monthly for 3 months, then .5 prn until 6 years	Total of all reporting groups
Overall Participants	20	20	40
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	9 45%	9 45%	18 45%
>=65 years	11 55%	11 55%	22 55%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.9 (15.7)	67.4 (11.3)	67.1 (12.5)
Sex: Female, Male (Count of Participants)
Female	7 35%	11 55%	18 45%
Male	13 65%	9 45%	22 55%
Region of Enrollment (participants) [Number]
United States	20 100%	20 100%	40 100%

Outcome Measures

1. Primary Outcome

Title	Best Corrected Visual Acuity Change From Baseline at All Visits
Time Frame	continuous through 72 mos

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CRVO	BRVO
Arm/Group Description	10 patients- RBZ dose level .5 for ITV injection given monthly for 3 months, then prn until 6 years 10 patients- RBZ dose level .3 for ITV injection given monthly for 3 months, then .5 prn until 6 years	10 patients- RBZ dose level .5 for ITV injection given monthly for 3 months, then prn until 6 years 10 patients- RBZ dose level .3 for ITV injection given monthly for 3 months, then .5 prn until 6 years
Measure Participants	10	9
Mean (Standard Deviation) [ETDRS letters]	10.5 (9.3)	15.1 (10.7)

2. Primary Outcome

Title	Retinal Thickness Change From Baseline at All Visits
Time Frame	continuous through 72 mos

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CRVO	BRVO
Arm/Group Description	10 patients- RBZ dose level .5 for ITV injection given monthly for 3 months, then prn until 6 years 10 patients- RBZ dose level .3 for ITV injection given monthly for 3 months, then .5 prn until 6 years	10 patients- RBZ dose level .5 for ITV injection given monthly for 3 months, then prn until 6 years 10 patients- RBZ dose level .3 for ITV injection given monthly for 3 months, then .5 prn until 6 years
Measure Participants	10	9
Mean (Standard Deviation) [microns]	-379.9 (239.1)	-216.9 (147.1)

Adverse Events

Time Frame	6 years
Arm/Group Title	CRVO		BRVO
Arm/Group Description	10 patients- RBZ dose level .5 for ITV injection given monthly for 3 months, then prn until 6 years 10 patients- RBZ dose level .3 for ITV injection given monthly for 3 months, then .5 prn until 6 years		10 patients- RBZ dose level .5 for ITV injection given monthly for 3 months, then prn until 6 years 10 patients- RBZ dose level .3 for ITV injection given monthly for 3 months, then .5 prn until 6 years
All Cause Mortality
	CRVO		BRVO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CRVO		BRVO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/20 (40%)		6/20 (30%)
Cardiac disorders
Transient Ischemic attack	1/20 (5%)	1	0/20 (0%)	0
Atrial Fibrillation	1/20 (5%)	1	0/20 (0%)	0
Mitral Valve surgery	1/20 (5%)	1	0/20 (0%)	0
Ear and labyrinth disorders
Scheduled surgery for hearing problem	0/20 (0%)	0	1/20 (5%)	1
Eye disorders
Vitrectomy	1/20 (5%)	1	0/20 (0%)	0
General disorders
Death (cause unknown)	2/20 (10%)	2	0/20 (0%)	0
Death	0/20 (0%)	0	1/20 (5%)	1
Infections and infestations
Pneumonia requiring hospitalization	1/20 (5%)	1	1/20 (5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Surgerical resection of breast cancer	0/20 (0%)	0	2/20 (10%)	2
Surgical resection of meningioma	1/20 (5%)	1	0/20 (0%)	0
Benign pancreatic mass surgery	0/20 (0%)	0	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	CRVO		BRVO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/20 (40%)		4/20 (20%)
Infections and infestations
Respiratory Infection	8/20 (40%)	10	4/20 (20%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.