Ranibizumab in Hemorrhagic Choroidal Neovascularization Trial

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00363168
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 7
• Location: 1
• Arms: 2
• Duration (Months): 33
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This research is being done to look at the effects of an experimental drug, ranibizumab, on a condition called "predominantly hemorrhagic subfoveal choroidal neovascularization (CNV)" due to wet age-related macular degeneration.

A predominantly hemorrhagic CNV lesion is diagnosed when at least 50% of the choroidal neovascular lesion is occupied by blood under the retina. We want to find out if injections of ranibizumab into the eye will help patients with this condition.

Condition or Disease	Intervention/Treatment	Phase
Choroidal Neovascularization	Drug: Ranibizumab; Drug: Ranibizumab	Phase 1

Detailed Description

This study is a randomized, interventional case series. A total of 10 patients, seen in the Retina Division of the Wilmer Eye Institute, will be enrolled. Subjects will be randomized to either 0.3 mg or 0.5 mg intravitreal injections of ranibizumab, which will be performed monthly for 3 doses. Further monthly injections are at the discretion of the examiner, and may be withheld if there is lack of continued improvement (defined as lack of improvement of at least 5 letters on an eye chart compared with 2 previous consecutive visits or lack of decrease of the retinal center point thickness of at least 50 microns compared with 2 previous consecutive visits) or complete success (defined as visual acuity of 20/20 or better or retinal center point thickness <225 microns).

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Ranibizumab in Hemorrhagic Choroidal Neovascularization Trial
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A 0.3 mg/0.05 ml dose of ranibizumab	Drug: Ranibizumab; 0.3 mg/0.05 ml dose; Other Names: Lucentis
Experimental: B 0.5 mg/0.05 ml dose of ranibizumab	Drug: Ranibizumab; 0.5 mg/0.05 ml dose; Other Names: Lucentis

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Avoiding 15 or More Letter Loss of Best Corrected Visual Acuity From Baseline to 12 Months on an Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Chart Measured at 4 Meters. [12 months]

   Visual acuity measured prior to first treatment with ranibizumab and at 12 months following the first treatment were compared for each subject enrolled in the study. The 12 month follow-up visual acuity was subtracted from the baseline visual acuity. Avoiding a 15 or more letter loss in visual acuity was considered a successful outcome.

Secondary Outcome Measures

1. Retinal Changes on Funduscopy [12 months]

2. Retinal Thickness Measured by Optical Coherence Tomography (OCT) [12 months]

3. Fluorescein Leakage on Fluorescein Angiography [12 months]

4. Number of Subjects Experiencing Complications Related to Drug or Its Administration [12 months after last injection]

   Potential complications included: Deterioration of best-corrected visual acuity by 3 or more lines Development of intraocular inflammation Development of elevated intraocular pressure Development of other ocular or systemic adverse effects. Subjects were monitored for potential drug-related ocular adverse effects: intraocular inflammation (uveitis), endophthalmitis, central retinal vein occlusion, transient elevation of IOP, acute reduction in the visual acuity, vitreous hemorrhage, injection-site pain, retinal hemorrhage, posterior vitreous detachment, and subconjunctival hemorrhage. Subjects were monitored for potential adverse effects of intravitreal injections: crystalline lens penetration, retinal break and/or detachment, vitreous hemorrhage, inflammation, and infection. Potential systemic adverse effects were captured by monitoring vital functions such as cardiovascular function, nervous system function, renal function, and gastrointestinal function.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Subjects will be eligible if the following criteria are met:

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

• Predominantly hemorrhagic subfoveal CNV (at least 50% of the lesion composed of hemorrhage) from age-related macular degeneration (AMD) resulting in visual acuity of 20/40 or worse.

• Age greater than 50 years.

• Participant must have media clear enough to permit fundus photography, fluorescein angiography, and optical coherence tomography.

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from this study:

• Known hypersensitivity to humanized monoclonal antibodies

• History (within past 6 months) or evidence of severe cardiac disease (apparent in electrocardiogram abnormalities, clinical history of unstable angina, acute coronary syndrome, myocardial infarction, revascularization procedure within 6 months prior to baseline, atrial or ventricular tachyarrhythmias requiring ongoing treatment).

• History of stroke within 6 months of study entry.

• Current acute ocular or periocular infection.

• Any major surgical procedure within one month of study entry.

• Known serious allergies to fluorescein dye.

• Previous participation in a clinical trial (for either eye) involving anti-angiogenic drugs (pegaptanib, ranibizumab, anecortave acetate, Protein Kinase C inhibitors, etc) within last 6 months.

• Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection or device implantation) in the study eye within the last 6 months.

• History of subfoveal laser treatment in the study eye.

• History of other visually-limiting conditions such as optic neuropathy, amblyopia, choroidal neovascularization due to causes other than AMD in the study eye.

• Ocular inflammation (including trace or above) in the study eye.

• Inability to comply with study or follow up procedures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Wilmer Eye Institute at Johns Hopkins	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Johns Hopkins University
• Genentech, Inc.

Investigators

• Principal Investigator: Neil M. Bressler, MD, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr. Neil M. Bressler, Principal Investigator, Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT00363168
• Other Study ID Numbers: NA_00001650
• First Posted: Aug 15, 2006
• Last Update Posted: Oct 19, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by Dr. Neil M. Bressler, Principal Investigator, Johns Hopkins University: Hemorrhagic Choroidal Neovascularization
• Additional relevant MeSH terms: Choroidal Neovascularization; Neovascularization, Pathologic; Ranibizumab

Study Results

Participant Flow

Arm/Group Title	Ranibizumab Dose A	Ranibizumab Dose B
Arm/Group Description	0.3 mg/0.05 ml intravitreal injection	0.5 mg/0.05 ml intravitreal injection
Period Title: Overall Study
STARTED	5	2
COMPLETED	5	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Ranibizumab Dose A	Ranibizumab Dose B	Total
Arm/Group Description	0.3 mg/0.05 ml intravitreal injection	0.5 mg/0.05 ml intravitreal injection	Total of all reporting groups
Overall Participants	5	2	7
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 20%	0 0%	1 14.3%
>=65 years	4 80%	2 100%	6 85.7%
Sex: Female, Male (Count of Participants)
Female	2 40%	0 0%	2 28.6%
Male	3 60%	2 100%	5 71.4%
Region of Enrollment (participants) [Number]
United States	5 100%	2 100%	7 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Avoiding 15 or More Letter Loss of Best Corrected Visual Acuity From Baseline to 12 Months on an Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Chart Measured at 4 Meters.
Description	Visual acuity measured prior to first treatment with ranibizumab and at 12 months following the first treatment were compared for each subject enrolled in the study. The 12 month follow-up visual acuity was subtracted from the baseline visual acuity. Avoiding a 15 or more letter loss in visual acuity was considered a successful outcome.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranibizumab Dose A	Ranibizumab Dose B
Arm/Group Description	0.3 mg/0.05 ml intravitreal injection	0.5 mg/0.05 ml intravitreal injection
Measure Participants	5	2
Number [participants]	5 100%	2 100%

2. Secondary Outcome

Title	Retinal Changes on Funduscopy
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Retinal Thickness Measured by Optical Coherence Tomography (OCT)
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Fluorescein Leakage on Fluorescein Angiography
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Number of Subjects Experiencing Complications Related to Drug or Its Administration
Description	Potential complications included: Deterioration of best-corrected visual acuity by 3 or more lines Development of intraocular inflammation Development of elevated intraocular pressure Development of other ocular or systemic adverse effects. Subjects were monitored for potential drug-related ocular adverse effects: intraocular inflammation (uveitis), endophthalmitis, central retinal vein occlusion, transient elevation of IOP, acute reduction in the visual acuity, vitreous hemorrhage, injection-site pain, retinal hemorrhage, posterior vitreous detachment, and subconjunctival hemorrhage. Subjects were monitored for potential adverse effects of intravitreal injections: crystalline lens penetration, retinal break and/or detachment, vitreous hemorrhage, inflammation, and infection. Potential systemic adverse effects were captured by monitoring vital functions such as cardiovascular function, nervous system function, renal function, and gastrointestinal function.
Time Frame	12 months after last injection

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranibizumab Dose A	Ranibizumab Dose B
Arm/Group Description	0.3 mg/0.05 ml intravitreal injection	0.5 mg/0.05 ml intravitreal injection
Measure Participants	5	2
Number [participants]	0 0%	0 0%

Adverse Events

Arm/Group Title	Ranibizumab Dose A		Ranibizumab Dose B
Arm/Group Description	0.3 mg/0.05 ml intravitreal injection		0.5 mg/0.05 ml intravitreal injection
All Cause Mortality
	Ranibizumab Dose A		Ranibizumab Dose B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ranibizumab Dose A		Ranibizumab Dose B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Ranibizumab Dose A		Ranibizumab Dose B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/2 (0%)

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.