Targeted Genetics Corp (SEATTLE, Washington) announced that the US FDA removed the hold, in place since July 2007, on the company's phase I/II clinical trial of tgACC94 for inflammatory arthritis. This action follows the agency's review of the safety data thus far on all 127 subjects and all data from a fatal serious adverse event (SAE), which led to the death of a patient.

The data obtained during the investigation indicates that tgAAC94 did not contribute to the patient's death, which was caused by disseminated histoplasmosis. Tests revealed that no amplification of viral vector occurred in the patient's body as a result of the investigational therapy, that only trace amounts of vector DNA were detected in tissues outside the treated joint, and that the amount of circulating TNF-α antagonist protein was as expected from the background therapy. The patient was on adalimumab, methotrexate, and prednisone, which are known to be immunosuppressive and a risk factor for histoplasma infection.

Targeted Genetics is revising the phase I/II trial's informed consent to include information about the SAE, to amend the protocol to exclude administration of tgAAC94 to patients presenting with fever (the patient who died had a mild fever at the time of drug administration), and to encompass additional suggestions made by the FDA and its independent data safety monitoring board. Over the next several weeks, the company will work with trial sites to obtain Institutional Review Board (IRB) approval of the amended protocol and revised informed consent and to reconsent the approximately 35 patients who have yet to receive the second injection of tgAAC94. All 127 adults had been randomized into three dose levels to receive a single intra-articular injection of either tgAAC94 or placebo into the knee, ankle, wrist, elbow, or metacarpophalangeal, followed by an open-label injection of tgAAC94 after 12 to 30 weeks, depending on when arthritis symptoms in the target joint meet criteria for reinjection. Patients in this trial will be followed for 30 weeks after the second injection. Targeted Genetics anticipates resuming the trial during the first quarter of 2008 and having full data from the phase I/II trial in the second half of 2008.

Initiation of a phase II trial of tgACC94 is also planned for the second half of 2008. The trial will evaluate efficacy and duration of response, as well as further assess safety, in patients with inflammatory arthritis who are not candidates for systemic protein therapy because they have one or a few inflamed joints, or they do not fully respond to systemic antiTNF-α protein therapy.