Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) announced results of a Phase 1 clinical trial of IMO-8400, a first-in-class antagonist of Toll-like Receptors (TLRs) 7, 8, and 9 being developed for potential applications in autoimmune and inflammatory diseases. In this trial, IMO-8400 was administered at single escalating dose levels and multiple dose levels weekly for four weeks in healthy subjects. IMO-8400 was well tolerated at all dose levels. IMO-8400-treated subjects showed inhibition of TLR 7-, 8-, and 9-mediated cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interferon-alpha (IFN-α), and other pro-inflammatory cytokines. These results were presented at the 13th Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS), held on June 27-30, 2013, in Boston, MA.
"We are very pleased with the safety and tolerability of IMO-8400 in this trial. Further, IMO-8400 showed strong and sustained inhibition of TLR7-, 8-, and 9- mediated cytokine induction," said Robert D. Arbeit, M.D., Vice President of Clinical Development. "Based on these encouraging results, we have initiated a randomized, double-blind, placebo-controlled Phase 2 trial of IMO-8400 in patients with psoriasis to evaluate PASI score improvement over a 12-week treatment period at three dose levels."
“We anticipate data from the ongoing Phase 2 trial to be available by year-end. Results from this study will inform our decisions regarding later stage clinical development of IMO-8400 in patients with psoriasis and clinical development in other indications,” said Sudhir Agrawal, D.Phil., Chairman and Chief Executive Officer. “IMO-8400 has potential applications in a broad range of autoimmune and inflammatory diseases, in which TLRs 7, 8, and 9 are implicated in exacerbating the disease.”
Phase 1 Clinical Trial Results
About the IMO-8400 Phase 1 Trial in Healthy Subjects
- IMO-8400 was well tolerated in single- and multiple-dose regimens at all dosages
- The intended pharmacodynamic mechanism of action was demonstrated in IMO-8400 treated subjects
- Cytokine induction mediated by TLRs 7, 8, and 9 was inhibited in IMO-8400 treated subjects and not in placebo treated subjects
- The induction of multiple cytokines was inhibited, including TNF-α, IL-1β, IL-6 and IFN-α
- Inhibition of cytokine induction was sustained for seven days after dosing with IMO-8400
- Pharmacokinetics showed IMO-8400 was rapidly cleared from plasma with no accumulation
- Pharmacodynamic results support a weekly dose regimen for evaluation of IMO-8400 in clinical development in autoimmune disease indications
A Phase 1 clinical trial of IMO-8400 was conducted to assess the safety, pharmacokinetic and pharmacodynamic activity in healthy subjects. This randomized, double-blind, placebo controlled trial enrolled 42 healthy subjects. The single-dose portion of the trial involved three escalating dose levels of 0.1, 0.3 and 0.6 mg/kg of IMO-8400 or placebo, with six subjects receiving each treatment. The multiple-dose portion of this trial involved two dose levels of IMO-8400, 0.3 and 0.6 mg/kg, and placebo, with six subjects receiving each treatment for four weekly doses. Safety and tolerability were monitored throughout the study. Pharmacokinetic activity and pharmacodynamic activity were monitored at specific times.