Table 4

Design of tgAAC94 trials


Number of patients



Cohort
 Dose (DNase-resistant particles)
 Drug
 Placebo
 Repeat dose (drug only)
 Endpoints
Phase I (RAC 2003)


Primary
1
 1010
 6
 2
     Safety
2
 1011
 6
 2
Secondary
3
 1012
 6
 2
     Changes in tenderness and swelling; injected and noninjected joints
4
 TBD
 6
 2
     American College of Rheumatology and Disease Activity Score scoring





     Joint fluid cell counts





     TNFR:Fc levels in joint fluid and serum





     Serum neutralizing antibodies to adeno-associated virus serotype 2





     Presence of tgAAC94 in peripheral blood mononuclear cells






Phase I/II (RAC 2007)



1
 1011
 15
 5
 20
 Primary
2
 1012
 15
 5
 20
      Safety
3
 1013
 15
 5
 20
 Secondary





     Tenderness and swelling of injected joint
4
 1011
 15
 5
 20
      Time to second injection of study drug
5
 1012
 15
 5
 20
      Overall disease activity
6
 1013
 15
 5
 20
      TNFR:Fc protein levels in serum and synovial fluid





     Serum anti-adeno-associated virus capsid neutralizing titers





Explore new outcome measures for single joints





     Patient assessment





     Functional assessment





     Joint inflammation and damage on magnetic resonance imaging (select subjects)

RAC = Recombinant DNA Advisory Committee; TBD, to be determined – the highest safe dose, as determined from cohorts 1 to 3; TNFR:Fc = tumor necrosis factor receptor:Fc domain of immunoglobulin fusion protein.

Evans et al. Arthritis Research & Therapy 2008 10:110   doi:10.1186/ar2411