MOLECULAR SYNOVECTOMY BY IN VIVO GENE TRANSFER: PHASE I TRIAL

Participants: A. A. Freiberg, B. Roessler, T. Laing

Keywords: Rheumatoid arthritis, human gene therapy, molecular synovectomy

Introduction

We propose initiation of a phase I dose escalation study of intraarticular pNGVL-TK plasmid DNA followed by systemic ganciclovir for the treatment of active rheumatoid synovitis of the knee. This trial will study 4 doses of plasma DNA over a range of 1_ logs (0.3mg, 1mg, 3.3mg, 10mg). A constant dose of intravenous ganciclovir (5mg per kg twice daily for 3 days) will be used for each dose of plasma DNA tested. We propose to study 2 patients at each dose of pNGVL-TK plasma DNA.

Inclusion Criteria

1) Proven diagnosis of rheumatoid arthritis, 2) Age greater than 18 years, male or female, 3) Duration of symptomatic disease — greater than 6 months, but less than 5 years, 4) stage of disease: patients with stage 2 or 3 disease is determined by ACR criteria, 5) Indications for surgical synovectomy-failure of disease affecting the knee to respond to appropriate medical treatment for a period of at least 6 months.

Exclusion Criteria

1) Pregnant women, 2) age less than 18, 3) daily dose of prednisone greater than 10mg per day or concomitant with treatment with Azathioprine cyclophosphamide, auranofin, 4) total granulocyte count less than 1,000 per mm ³, 5) bacterial cystitis, open skin wound.

Additional Criteria

Concomitant use of non-steroidal anti-inflammatory agents other than aspirin permitted.

Progress

Patients will be evaluated throughout the study including history and physical examination, complete clinical laboratory evaluation, power Doppler ultrasonography of the knee, and arthroscopy for synovial biopsy.