DESCRIPTION (Taken from the application): Funding is requested to plan a phase II clinical study of arthritis gene therapy. This study is an extension of a recently completed phase I clinical trial in which the human interleukin-1 receptor antagonist (IL-1Ra) cDNA was transferred to the metacarpophalangeal (MCP)joints of nine patients with end-stage rheumatoid arthritis (RA). By an ex vivo strategy employing a retrovirus (MFG-IRAP) and autologous synovial fibroblasts, it proved possible to transfer the IL1Ra gene to rheumatoid joints and to express them within those joints. No safety issues arose and all patients tolerated the procedure well. In making the transition from the completed phase I, safety study to the proposed phase II, efficacy study, it is necessary to make several modifications to the protocol. These include the need to introduce the gene into patients with earlier stage disease in order to determine any therapeutic effect of the procedure. It is proposed to study patient in whom active disease persists, despite having taken methotrexate for six months and Enbrel for three months. In addition to evaluating the patients by standard American College of Rheumatology criteria, the patients' joints will be assessed by magnetic resonance imaging, plain radiography, and histopathological analysis of synovial biopsies. Both knee joints and MCP joints will be used in the study. Gene expression will be assessed by measurement of IL-1 Ra concentrations in synovial fluid samples aspirated from knee joints. It is proposed to study ten patients in this fashion. Each patient will be studied for six months, by which time it will be possible to determine whether the gene treatment has had any effect on inflammatory or erosive events within the treated joints. Safety monitoring of the patients will continue annually for life, as required by the FDA.
|Effective start/end date||9/30/00 → 8/31/01|
- National Institutes of Health: $127,125.00