Ranibizumab for Neovascularization in Sickle Cell Retinopathy

Sickle Cell Anemia Clinical Trial

Official title:

A Phase I Study to Evaluate the Ocular and Non Ocular Safety of Ranibizumab in Treating Neovascularization Secondary to Sickle Cell Retinopathy

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00618644
• Other study ID #: 08-08
• Secondary ID: FVF4232s
• Status: Withdrawn
• Phase: N/A
• First received: February 7, 2008
• Last updated: September 25, 2012
• Start date: January 2010
• Est. completion date: June 2011

Study information

• Verified date: September 2012
• Source: Kresge Eye Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the ocular and non-ocular safety of a single dose of ranibizumab in treating neovascularization secondary to sickle cell retinopathy.

Description:

In the U.S., about 10% of African Americans have an abnormal hemoglobin gene. About 8% of African Americans are heterozygous for Hemoglobin S. In the United States, sickle cell anemia primarily occurs in the black population, with approximately 0.2% of African American children afflicted by this disease. It may be associated with other hemoglobinopathies as well. The prevalence in adults is lower because of the decrease in life expectancy. Systemically, the sickle cell anemia variation (SS) produces the most symptoms. With respect to the eye, the sickle cell disease mutation (SC) produces the most effects. Overall, the sickle cell trait expression (AS) produces the fewest complications.

• Among patients with SC or SThal, the incidence of proliferation sickle cell retinopathy is 33% and 14% respectively.

• Proliferative sickle cell retinopathy is the major cause of vision loss in sickle cell disease.

For sickle cell retinopathy, the commonly used therapeutic modalities include laser retinal photocoagulation, retinal cryotherapy, and vitrectomy/membranectomy depending on the severity of the disease. The most effective therapeutic modality with minimal postoperative complications appears to be scatter laser retinal photocoagulation.

A single case study of bevacizumab was found to effective in short term regression of neovascularization and improving vision after a single injection. Further study with ranibizumab is warranted.

Recent clinical trials (Marina and Anchor) have demonstrated that ranibizumab is effective in treating patients with CNV with age-related macular degeneration. Retinopathy in sickle cell disease has also been linked to VEGF. Therefore, patients with sickle cell retinopathy should respond to ranibizumab therapy.

This is an open-label single dose, phase I study of intravitreally administered ranibizumab in patients with sickle cell retinopathy.

Consented, enrolled subjects will receive a single open-label intravitreal injection of 0.5 mg ranibizumab.

Three subjects from one site in the United States will be enrolled.

Patients will receive one dose of 0.5 mg ranibizumab administered intravitreally.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with sickle cell anemia and retinopathy

• Over age 18 years

• Non-pregnant

Exclusion Criteria:

• Pregnant

• Glaucoma

• Patients using anticoagulants (e.g., warfarin)

• Retinal detachment

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Neovascularization, Pathologic
• Retinal Diseases
• Retinopathy
• Sickle Cell Anemia

Intervention

Drug:
• Ranibizumab
Ranibizumab 0.5 mg intravitreal injection

Locations

Country	Name	City	State
United States	Kresge Eye Institute	Detroit	Michigan

Sponsors (3)

Lead Sponsor	Collaborator
Kresge Eye Institute	Genentech, Inc., Wayne State University

Country where clinical trial is conducted

United States, 

References & Publications (7)

Al-Abdulla NA, Haddock TA, Kerrison JB, Goldberg MF. Sickle cell disease presenting with extensive peri-macular arteriolar occlusions in a nine-year-old boy. Am J Ophthalmol. 2001 Feb;131(2):275-6. — View Citation

Avery RL. Regression of retinal and iris neovascularization after intravitreal bevacizumab (Avastin) treatment. Retina. 2006 Mar;26(3):352-4. — View Citation

Chalam KV, Shah VA. Macular infarction a presentation of sickle cell crisis. Eye (Lond). 2004 Dec;18(12):1277-8. — View Citation

McLeod DS, Merges C, Fukushima A, Goldberg MF, Lutty GA. Histopathologic features of neovascularization in sickle cell retinopathy. Am J Ophthalmol. 1997 Oct;124(4):455-72. — View Citation

Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1419-31. — View Citation

Siqueira RC, Costa RA, Scott IU, Cintra LP, Jorge R. Intravitreal bevacizumab (Avastin) injection associated with regression of retinal neovascularization caused by sickle cell retinopathy. Acta Ophthalmol Scand. 2006 Dec;84(6):834-5. — View Citation

Witkin AJ, Rogers AH, Ko TH, Fujimoto JG, Schuman JS, Duker JS. Optical coherence tomography demonstration of macular infarction in sickle cell retinopathy. Arch Ophthalmol. 2006 May;124(5):746-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ocular safety of a single dose of ranibizumab		Three months	Yes
Secondary	Change in vision status		Three months	No
Secondary	To evaluate ocular hemorrhage		Three months.	Yes