Conditions: Plaque Psoriasis
Keywords: plaque psoriasis autoimmune disease Toll like receptor
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 46
Healthy volunteers: no

Brief summary:
IMO 8400 is a second-generation oligonucleotide antagonist of endosomal Toll-like receptors (TLR) 7, TLR8 and TLR9. These TLR react to complexes of exogenous nucleic acids (as might be encountered during infection) and endogenous nucleic acids (as might be released during tissue damage during autoimmune disease). In vitro and in multiple animal models of autoimmune disease, IMO-8400 blocks immune activation mediated through TLR7, 8 and 9. In Phase 1 studies (Protocol 8400-001) IMO 8400 has been administered to healthy adults by SC injection at single-doses and multiple-doses (4 weeks) up to 0.6 mg/kg. All treatments were well-tolerated, with mild injection site reactions and no pattern of systemic reactions or laboratory changes.

The current study represents the first clinical trial of IMO-8400 in patients with active autoimmune disease. Moderate to severe plaque psoriasis was chosen for this 12-week proof of activity trial based on a prior 4-week study using a first generation TLR7 and 9 antagonist which demonstrated clinical improvement in this patient population.

Detailed description:
Eligible subjects will be enrolled and randomized to receive one of the four treatments (three dose levels of IMO-8400 or Saline Placebo). Treatments will be administered once weekly by subcutaneous injections. Subjects will received treatment for 12 weeks and then be followed for an additional 6 weeks to assess the durability of the response.

Arms:
arm 1: IMO 8400 at 0.075 mg/kq q wk x 12 wks arm 2: IMO-8400 at 0.15 mg/kg q wk x 12 wks arm 3: IMO\_8400 at 0.3 mg/kg q wk x 12 wks arm 4: Saline (placebo) q wk x 12 wks arm 5: IMO\_8400 at 0.6 mg/kg q wk x 12 wks

Interventions: intervention 1: IMO-8400 Regimen 1 intervention 2: IMO-8400 Regimen 2 intervention 3: IMO-8400 Regimen 3 intervention 4: Saline Placebo intervention 5: IMO-8400 Regimen 4
Intervention descriptions: intervention 1: IMO-8400 0.075 mg/kg q wk x 12 wk by subcutaneous injection intervention 2: IMO-8400 0.15 mg/kg q wk x 12 wk by subcutaneous injection intervention 3: IMO-8400 0.3 mg/kg q wk x 12 wk by subcutaneous injection intervention 4: Saline q wk x 12 wk by subcutaneous injection intervention 5: IMO-8400 0.6 mg/kg q wk x 12 wk by subcutaneous injection

Protocol document: