Date: 2015-07-22
Type of information: Results
phase: 3
Announcement: results
Company: Xoma (USA - CA) Laboratoires Servier (France)
Product: gevokizumab ( XOMA 052/S 78989)
Action
mechanism: monoclonal antibody. Gevokizumab ( XOMA 052/S 78989) is a potent monoclonal antibody with unique allosteric modulating properties and the potential to treat patients with a wide variety of inflammatory diseases and other diseases. Gevokizumab binds strongly to interleukin-1 beta (IL-1 beta), a pro-inflammatory cytokine that has been shown to be involved in Behçet\'s and other forms of non-infectious uveitis, cardiovascular disease, and other auto-inflammatory diseases. In binding to IL-1 beta, gevokizumab inhibits the activation of the IL-1 receptor, thereby modulating the cellular signaling events that produce inflammation.
Disease: Behçet's uveitis
Therapeutic area: Ophtalmological diseases - Rare diseases
Country:
Trial
details: The global EYEGUARD-B study is designed to enroll 110 patients with a history of Behçet\'s disease uveitis with ocular involvement of the posterior segment who have experienced a recent ocular exacerbation that was treated successfully with high doses of corticosteroids. Patients will be randomized to either a 60mg dose of gevokizumab or placebo administered subcutaneously every four weeks on top of their current immunosuppressive and corticosteroid therapies.
The study\'s primary endpoint is the time to first acute ocular exacerbation, which will be measured once a predefined number of exacerbations have been observed. (NCT01965145)
Latest
news: * On July 22, 2015, Xoma, a leader in the discovery and development of therapeutic antibodies, announced the Phase 3 EYEGUARD-B study of gevokizumab in patients with Behçet's disease uveitis, run by its partner Servier did not meet the primary endpoint of time to first acute ocular exacerbation. The objective of the Phase 3 EYEGUARD-B study (A randomisEd, double-masked, placebo-controlled studY of the Efficacy of GevokizUmAb in the tReatment of patients with Behçet's Disease uveitis) was to demonstrate the superiority of gevokizumab, compared with placebo, on top of the current standard of care in reducing the risk of Behçet's disease uveitis exacerbations and to assess the safety of gevokizumab. The study was designed to enroll patients with a history of Behçet's disease uveitis with ocular involvement of the posterior segment who had experienced a recent ocular exacerbation that was treated successfully with high doses of corticosteroids. "Although the study did not achieve its main objective, we did see signals of drug activity such as preserved visual acuity, less severe ocular exacerbations and a reduced incidence of reported macular edema in patients treated with gevokizumab," said Paul Rubin MD, Senior Vice President Research and Development and Chief Medical Officer. "We will continue to work closely with our partner, Servier , and uveitis experts to conduct a thorough analysis of the data to fully understand gevokizumab's impact on several clinically relevant endpoints." "The initial observations seen in the secondary endpoints are clinically important and meaningful to both clinicians and Behçet's disease uveitis patients," stated Dr. Ilknur Tugal-Tutkun, international coordinator for the EYEGUARD-B study and Professor of Ophthalmology, Head, Ocular Immunology and Uveitis Service at Istanbul University , Istanbul Faculty of Medicine, Department of Ophthalmology . "We look forward to learning more." * On May 28, 2015, Xoma announced that the gevokizumab Phase 3 EYEGUARD-B study, sponsored by its development partner Servier , reached its target exacerbation event as specified in the study design. The objective of the first part of this study is to demonstrate the superiority of gevokizumab, as compared to placebo, on top of the current standard of care (immunosuppressant therapy and oral corticosteroids) in reducing the risk of Behçet's disease uveitis exacerbations and to assess the safety of gevokizumab. Servier now will begin the process of closing the clinical database and analyzing the data from this part of the study. Servier has provided a detailed schedule of the activities it will undertake to allow the locking of the database. The primary endpoint result is expected in approximately seven weeks. The trial is ongoing and remains double-masked for the extension period of the study. * On September 27, 2012, Xoma has announced its partner, Servier has received authorization to initiate the Servier -sponsored Behçet's uveitis Phase 3 clinical trial in several European countries. The study is titled A randomisEd, double-masked, placebo-controlled studY of the Efficacy of GevokizUmAb in the tReatment of patients with Behçet\'s Disease uveitis (EYEGUARD™-B). The objective of this study is to evaluate the efficacy of gevokizumab as compared to placebo on top of current standard of care (immunosuppressive therapy and oral corticosteroids) in reducing the risk of Behçet\'s disease uveitis exacerbations and to assess the safety of gevokizumab.
The trial enrolled a total of 83 patients in the core part of the study (40 on gevokizumab and 43 on placebo). Patients were randomized to either a 60 mg dose of gevokizumab or placebo administered subcutaneously once monthly on top of their current immunosuppressive and corticosteroid therapies. They were randomized when they reached the step of 20 mg/day equivalent oral prednisone and continued a standardized tapering regimen until they reached 5 mg/day during double-masked treatment.
The primary endpoint was the time to first acute ocular exacerbation. Secondary endpoints included total number of exacerbations, best corrected visual acuity, vitreous haze, retinal lesions, fundus assessments and macular edema. Gevokizumab appeared to be well tolerated in the trial. Adverse events were comparable between gevokizumab and placebo treated groups
