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Abstract Number: 2841

A Double-Blind, Placebo-Controlled, Phase 2 Trial of a Novel Toll-Like Receptor 7/8/9 Antagonist (IMO-8400) in Dermatomyositis

Yoo Jung Kim1, Elena Schiopu 2, Katalin Dankó 3, Tahseen Mozaffar 4, Srinivas Chunduru 5, Kirstin Lees 6, Namita Goyal 4, David Fiorentino 7 and Kavita Sarin 7, 1Stanford University School of Medicine, Redwood City, CA, 2Department of Rheumatology, University of Michigan, Ann Arbor, 3Department of Clinical Immunology, Medical Faculty, University of Debrecen, Debrecen, Hungary, 4Department of Neurology, University of California Irvine, Irvine, CA, 5Idera Pharmaceuticals, Inc., Cambridge, MA, 6Idera Pharmaceuticals, Inc., Cambridge, 7Department of Dermatology, Stanford University School of Medicine, Redwood City, CA

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: autoimmune diseases, Clinical research, dermatomyositis, drug treatment and inflammation

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Session Information

Date: Tuesday, November 12, 2019

Session Title: 5T113: Muscle Biology, Myositis & Myopathies II (2840–2845)

Session Type: ACR Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Dermatomyositis (DM) is a rare inflammatory disease of skin and muscle associated with characteristic skin findings, muscle weakness, interstitial lung disease, pruritus, and malignancies. Increased interferon (IFN) signaling is a prominent feature of DM, but the mechanisms leading to IFN production in DM are not understood. As toll-like receptor (TLR) 7/8/9 activation can lead to type I IFN production, TLR7/8/9 antagonism may provide therapeutic benefit in DM.

Methods: A double-blind, randomized, placebo-controlled, 24-week trial of IMO-8400 (a novel investigational oligonucleotide TLR7/8/9 antagonist [Idera Pharmaceuticals, Inc.]) was conducted with 30 eligible participants with definite or probable DM based on the criteria of Bohan and Peter. Participants were randomized to treatment with IMO-8400 0.6 mg/kg, IMO-8400 1.8 mg/kg, or placebo. The primary endpoint was the change in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score after 24 weeks of treatment. Exploratory analysis included type I IFN signaling as measured by a 10-gene expression score and patient-reported 5-D Itch Scale, a validated inventory for pruritus. Blood and skin samples were obtained at baseline and end of treatment to measure changes in type I IFN signaling.

Results: CDASI activity scores decreased in all trial arms by the end-of-trial visit, per repeated measures mixed model analysis: -9.3 in 0.6 mg/kg, -8.8 in 1.8 mg/kg, and -7.3 in placebo. We observed no change in skin and blood type I IFN signature scores or CDASI activity scores across treatment arms. We found an association between CDASI and skin IFN signature scores (β = 12.9, P = 0.0002), a moderate association between 5-D Itch Scale and skin IFN signature scores (Rho = 0.65, P < 0.0001), a lack of association between 5-D Itch Scale and blood IFN signature scores (Rho = 0.22, P = 0.24), and a positive correlated trend that did not reach significance between CDASI and 5-D Itch Scale scores. 5 patients experienced treatment-emergent adverse effects prompting discontinuation: 3 in low-dose (abdominal discomfort/flu, anxiety, urticaria), 1 in high-dose (thrombocytopenia), and 1 in placebo (muscle weakness).

Conclusion: IMO-8400 did not reach clinical efficacy in reducing cutaneous DM disease activity nor in decreasing the type I IFN signature in skin or blood, suggesting that TLR7/8/9 signaling may not play a causal role in IFN dysregulation in DM. Furthermore, our exploratory findings suggest that skin type I IFN signature scores provide a stronger indication of DM skin disease activity than blood type I IFN signature scores and that skin type I IFN signaling may be a pathway to target in improving pruritus symptoms in DM patients.


Disclosure: Y. Kim, None; E. Schiopu, None; K. Dankó, None; T. Mozaffar, aTyr, 2, 5, 9, Alnylam, 5, Alexion, 2, 5, 8, 9, Amicus, 2, 5, 9, Argenx, 2, 5, 9, Audentes, 5, 9, Sanofi-Genzyme, 2, 5, 8, 9, Sarepta, 5, Spark Therapeutics, 2, 5, 9, MT-Pharma, 5, 9, Ultragenyx, 5, 9, CSL Behring, 8, Grifols, 2, 8, Bristol-Myers-Squib, 2, Idera, 2, Ionis, 2, Momenta, 2, Ra Pharmaceuticals, 2, UCB Pharmaceuticals, 2, Valerion, 2; S. Chunduru, Idera Pharmaceuticals, 3, 4, 9; K. Lees, Idera Pharmaceuticals, 3; N. Goyal, None; D. Fiorentino, Janssen, 5, Pfizer, 2, 5, UCB Pharmaceuticals, 5; K. Sarin, None.

To cite this abstract in AMA style:

Kim Y, Schiopu E, Dankó K, Mozaffar T, Chunduru S, Lees K, Goyal N, Fiorentino D, Sarin K. A Double-Blind, Placebo-Controlled, Phase 2 Trial of a Novel Toll-Like Receptor 7/8/9 Antagonist (IMO-8400) in Dermatomyositis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/a-double-blind-placebo-controlled-phase-2-trial-of-a-novel-toll-like-receptor-7-8-9-antagonist-imo-8400-in-dermatomyositis/. Accessed January 28, 2023.
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