Study of Efalizumab Combined With Intravitreal Ranibizumab in the Treatment of Age-Related Macular Degeneration (SEIRA)
|First Received Date ICMJE||July 29, 2008|
|Last Updated Date||November 6, 2008|
|Start Date ICMJE||March 2008|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||• Safety and tolerability of 0.5 mg intravitreal dose of Ranibizumab in combination with 1 mg/kg/wk subcutaneous dose of Efalizumab in the treatment of age-related macular degeneration using the incidence and severity of adverse events through Month 6.|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00726466 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||The secondary outcomes of this study are as follows: • Mean change in ETDRS BCVA at Months 6 and 12. • Mean change in central retinal thickness per OCT at Months 6 and 12 • Mean change in lesion and CNV size as determined by FA at Months 6 and 12|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Study of Efalizumab Combined With Intravitreal Ranibizumab in the Treatment of Age-Related Macular Degeneration|
|Official Title ICMJE||A Phase I Study of the Inhibition of LFA-1 to Intercellular Adhesion Molecule-1 (ICAM-1) Using Subcutaneous Efalizumab Combined With Intravitreal Ranibizumab in the Treatment of Age-Related Macular Degeneration (SEIRA)|
Efalizumab is an immunosuppressive recombinant humanized IgG1 monocolonal antibody (150 Kd) that binds to human CD11a (1) and is used for the treatment of plaque psoriasis. Efalizumab was derived from the humanization of the murine efalizuman monoclonal antibody MHM24, which recognizes human and chimpanzee CD11a. Humanization of MHM24 was accomplished by grafting the murine complementarity determining regions (hypervariable region) into consensus human IgG1/ heavy and light chain sequences (Werther et al 1996). These same consensus human immunoglobulin sequences have been successfully used in the humanization of other murine antibodies, including those targeted to HER2 and IgE. Efalizumab inhibits the binding of LFA-1 to intercellular adhesion molecule-1 (ICAM-1) thereby inhibiting the adhesion of leukocytes to other cell types.
Ranibizumab is a recombinant, humanized, Fab fragment of a mouse monoclonal antibody targeted against VEGF. As VEGF binds to cellular receptors, it stimulates angiogenesis and vascular leakage. Blockade of VEGF by ranibizumab leads to reduced stimulation of cell proliferation and permeability resulting in inhibition of angiogenesis and decreased leakage. Ranibizumab intravitreal administration in neovascular AMD patients has been shown to effectively reduce vascular leakage and growth of CNV and to stabilize or improve visual function.
To further improve visual acuity, a combination therapy using efalizumab and ranibizumab is proposed. Efalizumab could target the adhesion factors that precede angiogenesis and improve the outcome for AMD patients in combination with the anti-VEGF agent, Ranibizumab.
This is an open-label, study of 0.5 mg intravitreal dose of Ranibizumab in combination with 1 mg/kg/wk subcutaneous dose of Efalizumab in in subjects with AMD. 10 subjects from 1 site will be enrolled in this study. Subject accrual into the trial is expected to be completed within 6 months.
All subjects will be evaluated monthly with a full ocular examination, visual acuity measurement (ETDRS chart at distance of 4 meters), OCT, and adverse event monitoring. Fluorescein Angiography (FA) and fundus photos will be done at BSL, Months 3, 6, 9 and 12.
Subjects will receive efalizumab 1mg/kg weekly subcutaneous injections for 24 weeks. Subcutaneous Efalizumab injections can be self administered after an initial teaching session in office on Day 0.
Subjects will receive six initial doses of 0.5 mg/eye intravitreous monthly injections of ranibizumab (Day 0, Months 1, 2, 3, 4 and 5) with scheduled follow-up visits monthly for 12 months. Re-treatment after the first six injections will be on an as-needed basis, based on predefined criteria.
3.2 RATIONALE FOR STUDY DESIGN
The rationale for the study is as follows:
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Efalizumab, Ranibizumab|
|Study Arm (s)||Experimental: I
This is an open-label, study of 0.5 mg intravitreal dose of Ranibizumab in combination with 1 mg/kg/wk subcutaneous dose of Efalizumab in in subjects with AMD.
Intervention: Drug: Efalizumab, Ranibizumab
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Withdrawn|
|Estimated Enrollment ICMJE||10|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||50 Years and older|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00726466|
|Other Study ID Numbers ICMJE||FVF4385s|
|Has Data Monitoring Committee||No|
|Responsible Party||Jason S. Slakter, MD, Vitreous Retina Macula Consultants of New York|
|Study Sponsor ICMJE||Vitreous -Retina- Macula Consultants of New York|
|Information Provided By||Vitreous -Retina- Macula Consultants of New York|
|Verification Date||November 2008|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP