Pilot Study of Ranibizumab (Lucentis) for Uveitic Cystoid Macular Edema

• Sponsor: University of Miami (Other)
• Overall Status: Completed
• CT.gov ID: NCT00826618
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 6
• Locations: 2
• Arm: 1
• Duration (Months): 63
• Patients Per Site: 3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Uveitic Cystoid Macular Edema (CME) is a major cause of visual loss associated with uveitis. Systemic and/or local corticosteroid therapy and systemic immunosuppression with steroid-sparing agents such as cyclosporine, methotrexate, azathioprine, or others, effectively treats uveitis and associated CME in many patients. However, in many cases, CME persists in spite of adequate suppression of uveitis. No consensus exists on how best to treat such cases. The further addition of immunosuppressive agents appears to have little effect on this form of CME. Oral corticosteroids are useful, but high dosage and prolonged use can be associated with serious side-effects. Periocular and intravitreal corticosteroid injections are associated with well-known, significant side effects such as glaucoma and cataract formation.

Vascular endothelial growth factor (VEGF) is suspected to play a role in the loss of vascular integrity in the eye and known to be induced by inflammatory cytokines, such as interleukin interleukin (IL)-1β and IL-6, which are elevated intraocularly in uveitis. In addition, it has been demonstrated that aqueous VEGF concentrations are statistically significantly higher in those uveitis patients with CME than those without CME. Inhibition of inappropriate VEGF activity is a potential approach to treatment of CME in uveitis given our current knowledge of the pathophysiology of this condition and also because of the clinical need for additional treatment options for these patients. Ranibizumab, a recombinant, humanized monoclonal antibody antigen-binding fragment (Fab) that neutralizes all active forms of VEGF-A, would target this pathway and may be useful in cases of persistent CME in uveitis patients.

The objective of this study is to determine if an anti-VEGF agent, Lucentis, is safe and effective in leading to regression of macular edema due to chronic non-infectious uveitis in patients with well-controlled uveitis.

Condition or Disease	Intervention/Treatment	Phase
Uveitic Cystoid Macular Edema	Drug: ranibizumab	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study of Ranibizumab (Lucentis) for Uveitic Cystoid Macular Edema
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ranibizumab	Drug: ranibizumab; This is an open-label, Phase I study of intravitreally administered 0.5mg ranibizumab in subjects with uveitic CME.; Other Names: Lucentis

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS at 4 Meters) at 12 Months. [1 year]

   Mean change in best corrected visual acuity (assessed by the ETDRS chart at 4 m) from baseline at 12 months following first intravitreal injection of ranibizumab was 12.2 ETDRS letters (P = 0.015).

Secondary Outcome Measures

1. The Mean Change in Best Corrected Visual Acuity (BCVA) (Assessed by the ETDRS Chart at 4 Meters) From Baseline at 12 Months Will be Computed With a T-test. [1 year]

2. The Percentage of Patients With 15 Letters (3 Lines) of Visual Acuity Improvement at 30, 60, 90, 120 Days, and 12 Months. [1 year]

3. The Mean Change in Foveal Retinal Thickness From Baseline at 7 Days, and at 30, 60, 90, 120 Days, and 12 Months Will be Computed Using a T-test. [1 year]

4. The Incidence of Ocular and Non-ocular Adverse Events Will be Evaluated Through Month 24. [2 years]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Subjects will be eligible if the following criteria are met:

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

2. Age > 18 years

3. Non-infectious uveitis in study eye.

4. Stable anti-uveitis medical regimen for at least one month prior to injection and controlled uveitis in the judgment of the investigator.

5. Vision 20/40 or worse in study eye.

6. Cystoid Macular Edema (CME) on fluorescein angiography (FA)

7. Optical Coherence Tomography (OCT) demonstrating thickness greater than 300 microns in the central subfield.

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

Only one eye will be assessed in the study. If both eyes are eligible, the investigator will determine which eye will be entered into the study.

Exclusion Criteria:

1. Previous intravitreal triamcinolone injection in study eye within 3 months of study injection.

2. Use of more than two glaucoma medicines for study eye.

3. Significant epiretinal membrane as judged by treating physician.

4. Evidence of vitreomacular traction on OCT.

5. Previous vitrectomy in study eye.

6. Pregnancy (positive pregnancy test) or lactation.

7. Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an intrauterine device (IUD), or contraceptive hormone implant or patch.

8. Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated.

9. Participation in another simultaneous IND trial.

10. Treatment for CME with intravitreal Lucentis, Macugen, or Avastin within 6 weeks prior to enrollment in this study.

11. Uncontrolled inflammation in the study eye.

12. Current vitreous hemorrhage.

13. Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.

14. Known allergy to any component of the study drug.

15. Intraocular pressure > 25 mm Hg despite treatment with glaucoma medications.

16. Blood pressure > 180/110 (systolic above 180 OR diastolic above 110). If blood pressure is brought below 180/110 by anti-hypertensive treatment, the subject can become eligible.

17. Major non-ocular surgery planned during the next 6 months.

18. Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated.

19. No Avastin use permitted in fellow eye during study.

20. Unwilling or unable to follow or comply with all study related procedures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bascom Palmer Eye Insitute	Miami	Florida	United States	33136
2	Bascom Palmer of the Palm Beaches	Palm Beach Gardens	Florida	United States	33418

Sponsors and Collaborators

• University of Miami
• Genentech, Inc.

Investigators

• Principal Investigator: Thomas A Albini, MD, University of Miami

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Thomas Albini, Associate Professor of Clinical Ophthalmology, University of Miami
• ClinicalTrials.gov Identifier: NCT00826618
• Other Study ID Numbers: FVF4148s
• First Posted: Jan 22, 2009
• Last Update Posted: Aug 26, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by Thomas Albini, Associate Professor of Clinical Ophthalmology, University of Miami: Uveitis; Cystoid Macular Edema
• Additional relevant MeSH terms: Macular Edema; Edema; Ranibizumab

Study Results

Participant Flow

Arm/Group Title	Ranibizumab
Arm/Group Description	ranibizumab: This is an open-label, Phase I study of intravitreally administered 0.5mg ranibizumab in subjects with uveitic CME.
Period Title: Overall Study
STARTED	6
COMPLETED	5
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Ranibizumab
Arm/Group Description	ranibizumab: This is an open-label, Phase I study of intravitreally administered 0.5mg ranibizumab in subjects with uveitic CME.
Overall Participants	5
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54 (19)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 60%
>=65 years	2 40%
Sex: Female, Male (Count of Participants)
Female	2 40%
Male	3 60%
Region of Enrollment (participants) [Number]
United States	5 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS at 4 Meters) at 12 Months.
Description	Mean change in best corrected visual acuity (assessed by the ETDRS chart at 4 m) from baseline at 12 months following first intravitreal injection of ranibizumab was 12.2 ETDRS letters (P = 0.015).
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranibizumab
Arm/Group Description	ranibizumab: This is an open-label, Phase I study of intravitreally administered 0.5mg ranibizumab in subjects with uveitic CME. Mean change in BCVA (assessed by the ETDRS chart at 4 m) from baseline at 12 months was 12.2 ETDRS letters (P = 0.015).
Measure Participants	5
Mean (Standard Deviation) [Change in ETDRS Letters]	12.2 (6.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ranibizumab
	Comments	Compare final visual acuity to baseline visual acuity
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0015
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	The Mean Change in Best Corrected Visual Acuity (BCVA) (Assessed by the ETDRS Chart at 4 Meters) From Baseline at 12 Months Will be Computed With a T-test.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	The Percentage of Patients With 15 Letters (3 Lines) of Visual Acuity Improvement at 30, 60, 90, 120 Days, and 12 Months.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	The Mean Change in Foveal Retinal Thickness From Baseline at 7 Days, and at 30, 60, 90, 120 Days, and 12 Months Will be Computed Using a T-test.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	The Incidence of Ocular and Non-ocular Adverse Events Will be Evaluated Through Month 24.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Ranibizumab
Arm/Group Description	ranibizumab: This is an open-label, Phase I study of intravitreally administered 0.5mg ranibizumab in subjects with uveitic CME.
All Cause Mortality
	Ranibizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ranibizumab
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	Ranibizumab
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Cardiac disorders
Tachycardia	1/5 (20%)
Eye disorders
Floaters	3/5 (60%)
Eye Pain	2/5 (40%)
Blurry Vision	2/5 (40%)
Uveitis in fellow eye	2/5 (40%)
Anterior uveitis	1/5 (20%)
Dry Eye	1/5 (20%)
Cataract	1/5 (20%)
Glaucoma	1/5 (20%)
Ocular pruritis	1/5 (20%)

Limitations/Caveats

The main limitation of this study is the small number of patients.There is no comparative arm to better define the relative efficacy of ranibizumab as compared with intraocular steroids or other treatments.

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.