Date: 2015-04-16
Type of information: Initiation of the trial
phase: 2
Announcement: initiation of the trial
Company: Actelion (Switzerland)
Product: ponesimod
Action
mechanism: immunomodulator/ S1P1 immunomodulator. Sphingosine-1-phosphate (S1P) is a sphingolipid released by erythrocytes, platelets, mast cells and other cell types. It is currently established that S1P stimulates at least five different cell surface resident G-protein coupled receptors (GPCRs) - S1P1,2,3,4, and 5. Activation of these GPCRs mediates a complex variety of biological responses such as lymphocyte migration, endothelial cell proliferation, blood vessel constriction and heart rate modulation. Ponesimod is an orally active, selective S1P1 immunomodulator. It prevents lymphocytes from leaving lymph nodes, thereby reducing circulating blood lymphocyte counts and preventing infiltration of lymphocytes into target tissues. The lymphocyte count reduction is rapid, dose-responsive, is sustained with continued dosing and quickly reversed upon discontinuation. Ponesimod does not cause lymphotoxicity: it does not destroy lymphocytes or interfere with their cellular function. Other blood cells e.g. cells of the innate immune system are unaffected and remain available to fight off infection. Ponesimod is therefore considered a promising new oral agent for the treatment of a variety of autoimmune disorders.
Disease: chronic graft-versus-host disease (GHVD)
Therapeutic area: Transplantation - Immunological diseases
Country: USA
Trial
details: Chronic graft versus host diseasre (GVHD) is a serious reaction that might occur in a person (the host) who has received cells or organs (graft) from another person because the graft attacks the host's cells. Currently there are no approved therapies for chronic GVHD in the USA, and patients with chronic GVHD are treated with immunosuppressant drugs. T-lymphocytes are likely to play a role in the development of chronic GVHD. Due to the capacity of ponesimod to block the traffic of T-lymphocytes, ponesimod may be a new therapeutic approach to treat chroninc GVHD. This phase 2, open-label, single-arm, intra-subject dose-escalation studywill investigate the biological activity, safety, tolerability, and pharmacokinetics of ponesimod in subjects with symptomatic moderate or severe chronic GVHD inadequately responding to first or second line therapy. The main objective of this study is to assess the effectiveness and safety of several doses of ponesimod in subjects with chronic GVHD who did not respond to standard available treatments.(NCT02461134)
Latest
news: * On April 16, 2015, Actelion announced that it is accelerating its clinical development efforts in the field of immunological disorders, following a broad scientific, medical and commercial evaluation of a series of its selective S1P1 receptor modulators, discovered in-house. Actelion will initiate a Phase II study with ponesimod in patients suffering from chronic graft versus host disease. This Phase II, open-label, single-arm, intra-subject dose-escalation study will investigate the biological activity, safety, tolerability, and pharmacokinetics of ponesimod in subjects with symptomatic moderate or severe chronic graft vs. host disease inadequately responding to first or second line therapy. The study will also investigate the clinical response to ponesimod treatment in these patients. Approximately 30 subjects will be enrolled to receive ponesimod in escalating doses of 5, 10 and 20 mg/day over the course of 24 weeks. The study will be conducted at approximately 10 sites in the US and is expected to last approximately 18 months.
