RAVEN: Intravitreal Ranibizumab 0.5MG, or 1.0mg for RVO With Macular Edema Previously Receiving Bevacizumab

• Sponsor: Hanscom, Thomas, M.D. (Other)
• Overall Status: Completed
• CT.gov ID: NCT01471691
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 14
• Locations: 4
• Arms: 2
• Duration (Months): 27
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study examines two doses of Ranibizumab (0.5mg and 1.0mg) for the treatment of macular edema secondary to retinal vein occlusion in patients that have previously failed treatment with other macular edema treatments including bevacizumab.

Condition or Disease	Intervention/Treatment	Phase
Branch Retinal Vein Occlusion; Central Retinal Vein Occlusion; Macular Edema	Drug: ranibizumab 0.5mg; Drug: ranibizumab 1.0mg	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II, Open-label, Study of Intravitreal RAnibizumab 0.5MG, or High Dose 1.0mg for Retinal Vein Occlusions With rEfractory Macular Edema Previously Receiving iNtravitreal Bevacizumab (RAVEN)
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: intravitreal ranibizumab 0.5mg	Drug: ranibizumab 0.5mg; Standard dose; Other Names: Lucentis
Experimental: intravitreal ranibizumab 1.0mg	Drug: ranibizumab 1.0mg; High dose; Other Names: Lucentis

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline BCVA [Baseline to month 6]

   Vision was measured using a standard ETDRS chart at baseline and each subsequent monthly visit.

Secondary Outcome Measures

1. Mean Change From Baseline in Center Point Thickness [months 1-12]

2. Change in Mean Best Corrected Visual Acuity From Baseline [months 1-12]

3. Percentage of Patients With CFT Less Than 300um [Month 6 and 12]

4. Excess Foveal Thickness [Month 6 and 12]

5. Total Number of Ranibizumab Injections [month 12]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Ability to provide written informed consent and comply with study assessments for the full duration of the study

• Age > 18 years

• CRVO or BRVO diagnosis

• For CRVO, clinical evidence of perfused central retinal vein occlusion. A CRVO is defined as an eye that has retinal hemorrhages and a dilated retinal venous system in all 4 quadrants. Other evidence of a CRVO may include telangiectatic capillary bed and collateral vessels at the optic nerve head.

• Central macular edema present on clinical examination and OCT testing with a central point thickness and/or central 1mm subfield thickness > 300 microns after at least 3 months of bevacizumab or steroid therapy.

• Visual acuity score greater than or equal to 19 letters (20/400) and less than or equal to 73 letters (20/40) by the ETDRS visual acuity protocol.

• Patients must demonstrate that they are no longer improving on bevacizumab or intravitreal steroid therapy (i.e. no improvement in acuity in 2 consecutive visits)

• BRVO patients treated with grid laser must show residual edema three months following latest laser treatment

• Media clarity, pupillary dilation and patient cooperation sufficient to allow OCT testing and retinal photography

Exclusion Criteria:

• Pregnancy (positive pregnancy test) or known to be pregnant; also pre-menopausal women not using adequate contraception.

• Participation in another ocular investigation or trial simultaneously

• Any condition that, in the opinion of the investigator, would preclude participation in the study (e.g. chronic alcoholism, drug abuse)

• Significant diabetic retinopathy (greater than moderate NPDR) or macular edema associated with diabetic retinopathy

• An eye that, in the investigator's opinion, has no chance of improving in visual acuity following resolution of macular edema (e.g. presence of subretinal fibrosis or geographic atrophy or severe epiretinal membrane)

• Presence of another ocular condition that may affect the visual acuity or macular edema during the course of the study (e.g. AMD, uveitis, Irvine-Gas)

• Evidence of neovascularization of the iris or retina (presence of ischemic CRVO/BRVO)

• Evidence of central atrophy or fibrosis in the study eye

• Presence of substantial cataract, one that might decrease the vision by 3 or more lines of vision at sometime during the study.

• History of grid/focal laser or panretinal laser in the study eye in the previous three months

• History of vitreous surgery in the study eye

• History of use of intravitreal, peribulbar, or retrobulbar steroids within three months of the study.

• History of cataract surgery within 6 months of enrollment.

• History of YAG capsulotomy within 2 months of the surgery.

• Visual acuity <20/400 in the fellow eye

• Uncontrolled glaucoma (pressure >30) despite treatment with glaucoma medications.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	South Coast Retina	Huntington Beach	California	United States	92647
2	South Coast Retina	Long Beach	California	United States	90807
3	Thomas Hanscom AMC	Santa Monica	California	United States	90404
4	South Coast Retina	Torrance	California	United States	90505

Sponsors and Collaborators

• Hanscom, Thomas, M.D.
• Genentech, Inc.

Investigators

• Principal Investigator: Thomas O'Hearn, MD, Thomas Hanscom AMC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hanscom, Thomas, M.D.
• ClinicalTrials.gov Identifier: NCT01471691
• Other Study ID Numbers: ML27847
• First Posted: Nov 16, 2011
• Last Update Posted: Apr 29, 2015
• Last Verified: Apr 1, 2015

• Additional relevant MeSH terms: Macular Edema; Retinal Vein Occlusion; Edema; Ranibizumab

Study Results

Participant Flow

Arm/Group Title	Intravitreal Ranibizumab 0.5mg	Intravitreal Ranibizumab 1.0mg
Arm/Group Description	ranibizumab 0.5mg: Standard dose Patients were given six months of monthly treatment with the standard 0.5mg ranibizumab dose, followed by six months of evaluation and PRN treatment based upon pre-specified criteria.	ranibizumab 1.0mg: High dose Patients were given six months of monthly treatment with the 1.0mg ranibizumab dose, followed by six months of evaluation and PRN treatment based upon pre-specified criteria.
Period Title: Overall Study
STARTED	8	6
COMPLETED	8	5
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Intravitreal Ranibizumab 0.5mg	Intravitreal Ranibizumab 1.0mg	Total
Arm/Group Description	ranibizumab 0.5mg: Standard dose	ranibizumab 1.0mg: High dose	Total of all reporting groups
Overall Participants	8	6	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73 (5.0)	78 (5.0)	75 (5.0)
Sex: Female, Male (Count of Participants)
Female	7 87.5%	2 33.3%	9 64.3%
Male	1 12.5%	4 66.7%	5 35.7%
Region of Enrollment (participants) [Number]
United States	8 100%	6 100%	14 100%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline BCVA
Description	Vision was measured using a standard ETDRS chart at baseline and each subsequent monthly visit.
Time Frame	Baseline to month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravitreal Ranibizumab 0.5mg	Intravitreal Ranibizumab 1.0mg
Arm/Group Description	ranibizumab 0.5mg: Standard dose	ranibizumab 1.0mg: High dose
Measure Participants	8	5
Mean (Standard Deviation) [Letters (ETDRS chart)]	14 (10)	5 (6)

2. Secondary Outcome

Title	Mean Change From Baseline in Center Point Thickness
Time Frame	months 1-12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Change in Mean Best Corrected Visual Acuity From Baseline
Time Frame	months 1-12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Percentage of Patients With CFT Less Than 300um
Time Frame	Month 6 and 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Excess Foveal Thickness
Time Frame	Month 6 and 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Total Number of Ranibizumab Injections
Time Frame	month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Intravitreal Ranibizumab 0.5mg		Intravitreal Ranibizumab 1.0mg
Arm/Group Description	ranibizumab 0.5mg: Standard dose		ranibizumab 1.0mg: High dose
All Cause Mortality
	Intravitreal Ranibizumab 0.5mg		Intravitreal Ranibizumab 1.0mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Intravitreal Ranibizumab 0.5mg		Intravitreal Ranibizumab 1.0mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/8 (25%)		0/6 (0%)
Ear and labyrinth disorders
Ruptured Retinal Macroaneurysm	1/8 (12.5%)	1	0/6 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer	1/8 (12.5%)	1	0/6 (0%)	0
Other (Not Including Serious) Adverse Events
	Intravitreal Ranibizumab 0.5mg		Intravitreal Ranibizumab 1.0mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.