Date: 2016-01-06
Type of information: Recruitment of the first patient
phase: 2
Announcement: clinical trial authorization
Company: FibroGen (USA - CA)
Product: pamrevlumab (FG-3019)
Action
mechanism: monoclonal antibody. FG-3019 is an investigational therapeutic antibody developed by FibroGen to inhibit the activity of connective tissue growth factor (CTGF), a common factor in chronic fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. In Duchenne muscular dystrophy, muscle cells are damaged due to the absence of the dystrophin protein complex necessary for normal muscle fiber function. Absence of dystrophin leads to muscle damage, inflammation, fibrosis, and progressive dysfunction and weakness in the muscles of DMD patients. The extent of diminished muscle function directly correlates with the extent of intra-muscular fibrosis. The rationale for FG-3019 in DMD is based on data that show CTGF reduces the ability of damaged muscle cells to repair themselves and promotes muscle fibrosis. In preclinical studies, FG-3019 reduced muscle fibrosis and significantly improved muscle function. Separately, in clinical trials of another fibrotic condition, idiopathic pulmonary fibrosis, FG-3019 was shown to reverse fibrosis in a significant proportion of patients.
Disease: Duchenne muscular dystrophy
Therapeutic area: Rare diseases - Genetic diseases - Neuromuscular diseases
Country: USA
Trial
details: The open-label, single-arm Phase 2 study will evaluate the safety and efficacy of FG-3019 in up to 22 non-ambulatory DMD patients who are at least 12 years of age. Each patient will receive FG-3019 (35 mg/kg, every two weeks) for up to two years. All patients will receive full supportive care as required by their clinical condition and will be closely monitored for safety. Efficacy endpoints include changes in pulmonary function, upper body muscle strength, cardiac fibrosis, and other measures. Efficacy assessments will be performed routinely over the course of the study, including pulmonary and muscle function tests approximately every four months and MRIs once a year. An interim analysis of safety and efficacy will be performed after all evaluable subjects complete one year of dosing. If the interim analysis indicates a potential benefit from FG-3019, the study will be extended to two years. (NCT02606136)
Latest
news: * On January 6, 2016, FibroGen announced enrollment of the first two patients in an open-label, multicenter Phase 2 clinical trial of FG-3019 in patients with Duchenne muscular dystrophy (DMD). This monoclonal antibody against connective tissue growth factor (CTGF) was studied in an open-label Phase 2 clinical study in 89 patients with idiopathic pulmonary fibrosis (IPF) and is being further evaluated in a randomized placebo-controlled Phase 2 study in IPF. Results from the open-label study have supported further investigation of the potential of FG-3019 to treat fibrotic disease. Research on the relationship of DMD and CTGF conducted by FibroGen and others has shown that CTGF over-expression in muscle of normal mice caused extensive skeletal muscle damage, fibrosis, and decreased muscle strength. CTGF inhibits muscle cell differentiation, the normal biological process in which muscle cells are formed, and causes de-differentiation, or the breakdown, of mature muscle cells. Elevated levels of CTGF are also seen in the muscle of DMD patients. - The potential to slow the loss of, stabilize, or regain diaphragm and intercostal muscle strength and thereby preserve or improve pulmonary function in non-ambulatory DMD patients. By the time DMD patients lose ambulation, their pulmonary function has steadily declined to a point where many require pulmonary assistance. Pulmonary function will be the primary efficacy assessment of the trial. - The potential to slow the loss of, stabilize, or regain upper body muscle strength and thereby preserve the ability of DMD patients to use their arms for normal daily functions. As the disease progresses, patients’ ability to use arms and hands declines steadily. Forearm muscle fibrosis will be measured by MRI in the trial as well as by functional assays of strength and mobility. - The potential to slow, stabilize, or reverse cardiomyopathy. As in skeletal muscle, fibrosis progresses steadily in the heart muscles of DMD patients. Cardiomyopathy is the cause of death for many DMD patients. Cardiac fibrosis and function will be evaluated by MRI in the study. * On July 27, 2015, FibroGen announced that the FDA has completed the review of its investigational new drug (IND) application for the study of FG-3019 in patients with Duchenne muscular dystrophy, and clinical study may proceed. FG-3019 is a fully human monoclonal antibody that inhibits the activity of connective tissue growth factor (CTGF), a common mediator of fibrotic disease. FG-3019 is currently in Phase 2 clinical studies for idiopathic pulmonary fibrosis and pancreatic cancer. The IND enables FibroGen to initiate a multi-site Phase 2 trial exploring FG-3019 for the treatment of DMD in non-ambulatory patients, scheduled to begin later this year. This submission is the culmination of nearly 10 years of research by FibroGen and its collaborators to understand the role of CTGF in DMD. Data from these investigations, including the testing of FG-3019 in preclinical models of DMD, have appeared in several peer reviewed publications.FibroGen has met with panels of international muscular dystrophy experts, including the TREAT-NMD Advisory Committee for Therapeutics, to review these findings, discuss the rationale for FG-3019 as a potential treatment for DMD, and refine the clinical trial design. There has been consistent support in these panels for the advancement of FG-3019 development in DMD. FibroGen plans to initiate its first DMD trial at US sites and begin enrolling non-ambulatory subjects this year.
The Phase 2 clinical study of non-ambulatory DMD patients evaluates the therapeutic potential of FG-3019 in three areas:
