– Subjects were rapidly recruited and consistently retained and dosed –
– No concerning safety signals were identified –
– Imaging data from SIGNAL Cohort A indicate treatment effect on preservation of brain structure and metabolic activity –
Vaccinex, Inc., a privately-held clinical-stage biotechnology company engaged in the discovery and development of therapeutic monoclonal antibodies to treat patients with cancer and neurodegenerative diseases, announced today that a pre-planned analysis of data from Cohort A of the SIGNAL trial was completed. In June 2015, Vaccinex, the Huntington Study Group (HSG), and the University of Rochester’s Clinical Trials Coordination Center launched SIGNAL, the first clinical trial to investigate a monoclonal antibody as a potential treatment for Huntington’s disease (HD).
The SIGNAL trial is a Phase 2, multi-center, randomized, double-blinded, placebo controlled study in subjects with late prodromal and early manifest HD to assess the safety, tolerability, pharmacokinetics, and efficacy of VX15/2503 (“VX15”), an antibody to semaphorin 4D, a molecule that has been shown to regulate the activation and migration of inflammatory cells and to inhibit differentiation of oligodendrocyte precursors in the brain. The study consists of two Cohorts, A and B. Thirty-six participants were randomized into the now completed Cohort A to receive monthly infusions of either VX15 or placebo for six months, in a double-blind fashion. All participants in Cohort A subsequently received open-label VX15 for another five months, followed by a three-month safety follow-up.
A significant relationship between decreasing imaging measures and disease progression in HD was previously demonstrated in the much larger PREDICT-HD and TRACK-HD studies (1-3). A major focus of the present SIGNAL study, therefore, includes the use of brain imaging measures, Magnetic Resonance Imaging (MRI) and fluorodeoxyglucose (FDG)-positron emission tomography (PET, FDG-PET), in order to investigate the impact of treatment on changes in brain structure (MRI) and metabolic activity (FDG-PET). Cohort A participants in the SIGNAL study underwent imaging at baseline and after 6 and 11 months of treatment. A second goal of the study was to collect data on the variance of potential treatment effects of VX15 on quantitative motor and cognitive assessments so as to project the required group size for investigation of such effects in Cohort B.
Analysis of imaging data from subjects in Cohort A suggests that treatment with the VX15 antibody moderates or prevents the decrease in MRI volume and metabolic activity in many brain cortical regions which otherwise decreased at an annualized rate of 2% to 3% in the placebo control group. Similar imaging changes were detected in both early manifest and late prodromal subjects, particularly as regards changes in metabolic activity. Although only 36 subjects were enrolled in Cohort A and the duration of treatment was relatively short, the data encourage further investigation of clinical effects of treatment. Accordingly, the results of motor and cognitive assessments provided important guidance for projecting the group size required to detect clinical effects in the continuing Cohort B study.
The SIGNAL trial is based on prior research on neurodegenerative disease mechanisms, where it was demonstrated in preclinical models that semaphorin 4D (“SEMA4D”) triggers activation of both microglia and astrocytes, the main innate inflammatory cells of the central nervous system (4,5). Chronic activation of microglia and astrocytes has been implicated as a potentially important disease mechanism in HD, progressive multiple sclerosis (“MS”) and other neurodegenerative disorders. VX15 antibody is designed to block the functional activity of SEMA4D.
Dr. Maurice Zauderer, President and Chief Executive Officer of Vaccinex, said:
“We believe that preliminary imaging measures in Cohort A of our SIGNAL clinical trial have provided an early indication of potential benefit of VX15 in HD. These data have provided important direction to the design and prospective designation of clinical endpoints for the continuing Cohort B.”
For more information about the SIGNAL trial and enrollment, visit the Huntington Study Group website, www.huntingtonstudygroup.org.
Source: Vaccinex, Inc