DESCRIPTION (provided by applicant): Funding is requested to plan a clinical study in which the human interleukin-1 receptor antagonist (IL-1Ra) cDNA will be transferred to the knee joints of subjects with advanced osteoarthritis (OA). This builds upon our accumulated experience in gene transfer to joints, in particular the recently completed phase I study in which the IL-1Ra cDNA was transferred to the metacarpophalangeal joints of subjects with rheumatoid arthritis (RA). What is novel about the proposed study in patients with OA, is the ability to measure the level and duration of transgene expression within human joints, something that has not been possible previously. It is proposed to recruit 18 participants requiring staged bilateral total knee replacements because of OA. Equal numbers will be randomly entered into gene transfer and control groups. The first knee replacement surgery will provide autologous synovium from each subject. Synovial cells will be cultured ex vivo. Cells from experimental groups will be transduced with high titer retrovirus carrying the IL-1Ra cDNA. Control cells will be mock transduced. In a dose-escalation manner, transduced or untransduced cells, depending on the group, will be injected into the contralateral knee joints of each patient 3 months before these joints are surgically replaced. During this time the joints will be aspirated to enable measurement of the level and duration of transgene expression. Fluids will also be examined for evidence of a biological response to the transgene. Synovial fluid, blood and urine will be archived. Although no clinical response is expected, patients will undergo a WOMAC and X-ray analysis. The proposed planning period will be spent finalizing the details of this study, including the statistical power analysis, generating a manual of operations and procedures, planning and attending a pre-IND meeting with the FDA and writing the appropriate documents for the IRB, IBC, RAC and FDA.
|Effective start/end date||9/30/02 → 5/31/03|
- National Institutes of Health: $172,997.00