A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients with active moderate to severe Crohn's disease

Robert Burakoff, Charles F. Barish, Dennis Riff, Ronald Pruitt, William Y. Chey, Francis A. Farraye, Ira Shafran, Seymour Katz, Charles L. Krone, Martha Vander Vliet, Christopher Stevens, Matthew L. Sherman, Eric Jacobson, Ronald Bleday

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    Abstract

    BACKGROUND: Intestinal inflammation associated with Crohn's disease is characterized by a type 1 helper T cell response and elevated levels of interleukin (IL)-12. We report our clinical experience with a novel oral IL-12/IL-23 inhibitor (STA 5326) for the treatment of active Crohn's disease. MATERIALS AND METHODS: We conducted an open-label, dose-escalating trial of the orally delivered small molecule immunomodulator STA 5326 in 73 patients with active Crohn's disease (Crohn's disease activity index [CDAI] 220-450, inclusive). Five cohorts of patients were treated for up to 4 weeks with 14 mg twice a day (bid), 35 mg daily (qd), 28 mg bid, 35 mg bid, or 70 mg qd. The endpoints of the study included safety and improvement in clinical activity measured by the CDAI and the Crohn's disease endoscopic index of severity. RESULTS: STA 5326 was well tolerated. Reported adverse events were similar across dose cohorts. The most common (>15%) drug-related adverse events observed were dizziness, nausea, headache, and fatigue. Clinical activity at day 28/29 was observed at qd doses of 28 mg and above for the clinical endpoints of response and remission: 70 points or greater decrease in CDAI (range 42%-82% of patients); 100 points or greater decrease in CDAI (range 38%-64% of patients), and CDAI <150 (range 15%-36%). CONCLUSIONS: Oral qd dosing of STA 5326 for 4 weeks was well tolerated in doses up to 70 mg qd in patients with active moderate to severe Crohn's disease. Clinical activity was observed at qd doses of 28 mg and above.

    Original languageEnglish (US)
    Pages (from-to)558-565
    Number of pages8
    JournalInflammatory Bowel Diseases
    Volume12
    Issue number7
    DOIs
    StatePublished - Jul 1 2006

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    Interleukin-23
    Interleukin-12
    Crohn Disease
    apilimod mesylate
    Th1 Cells
    Immunologic Factors
    Dizziness
    Drug-Related Side Effects and Adverse Reactions
    Nausea
    Fatigue
    Headache
    Inflammation

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Gastroenterology

    Cite this

    A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients with active moderate to severe Crohn's disease. / Burakoff, Robert; Barish, Charles F.; Riff, Dennis; Pruitt, Ronald; Chey, William Y.; Farraye, Francis A.; Shafran, Ira; Katz, Seymour; Krone, Charles L.; Vander Vliet, Martha; Stevens, Christopher; Sherman, Matthew L.; Jacobson, Eric; Bleday, Ronald.

    In: Inflammatory Bowel Diseases, Vol. 12, No. 7, 01.07.2006, p. 558-565.

    Research output: Contribution to journalArticle

    Burakoff, R, Barish, CF, Riff, D, Pruitt, R, Chey, WY, Farraye, FA, Shafran, I, Katz, S, Krone, CL, Vander Vliet, M, Stevens, C, Sherman, ML, Jacobson, E & Bleday, R 2006, 'A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients with active moderate to severe Crohn's disease', Inflammatory Bowel Diseases, vol. 12, no. 7, pp. 558-565. https://doi.org/10.1097/01.ibd.0000225337.14356.31
    Burakoff, Robert ; Barish, Charles F. ; Riff, Dennis ; Pruitt, Ronald ; Chey, William Y. ; Farraye, Francis A. ; Shafran, Ira ; Katz, Seymour ; Krone, Charles L. ; Vander Vliet, Martha ; Stevens, Christopher ; Sherman, Matthew L. ; Jacobson, Eric ; Bleday, Ronald. / A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients with active moderate to severe Crohn's disease. In: Inflammatory Bowel Diseases. 2006 ; Vol. 12, No. 7. pp. 558-565.
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    abstract = "BACKGROUND: Intestinal inflammation associated with Crohn's disease is characterized by a type 1 helper T cell response and elevated levels of interleukin (IL)-12. We report our clinical experience with a novel oral IL-12/IL-23 inhibitor (STA 5326) for the treatment of active Crohn's disease. MATERIALS AND METHODS: We conducted an open-label, dose-escalating trial of the orally delivered small molecule immunomodulator STA 5326 in 73 patients with active Crohn's disease (Crohn's disease activity index [CDAI] 220-450, inclusive). Five cohorts of patients were treated for up to 4 weeks with 14 mg twice a day (bid), 35 mg daily (qd), 28 mg bid, 35 mg bid, or 70 mg qd. The endpoints of the study included safety and improvement in clinical activity measured by the CDAI and the Crohn's disease endoscopic index of severity. RESULTS: STA 5326 was well tolerated. Reported adverse events were similar across dose cohorts. The most common (>15{\%}) drug-related adverse events observed were dizziness, nausea, headache, and fatigue. Clinical activity at day 28/29 was observed at qd doses of 28 mg and above for the clinical endpoints of response and remission: 70 points or greater decrease in CDAI (range 42{\%}-82{\%} of patients); 100 points or greater decrease in CDAI (range 38{\%}-64{\%} of patients), and CDAI <150 (range 15{\%}-36{\%}). CONCLUSIONS: Oral qd dosing of STA 5326 for 4 weeks was well tolerated in doses up to 70 mg qd in patients with active moderate to severe Crohn's disease. Clinical activity was observed at qd doses of 28 mg and above.",
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    T1 - A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients with active moderate to severe Crohn's disease

    AU - Burakoff, Robert

    AU - Barish, Charles F.

    AU - Riff, Dennis

    AU - Pruitt, Ronald

    AU - Chey, William Y.

    AU - Farraye, Francis A.

    AU - Shafran, Ira

    AU - Katz, Seymour

    AU - Krone, Charles L.

    AU - Vander Vliet, Martha

    AU - Stevens, Christopher

    AU - Sherman, Matthew L.

    AU - Jacobson, Eric

    AU - Bleday, Ronald

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    N2 - BACKGROUND: Intestinal inflammation associated with Crohn's disease is characterized by a type 1 helper T cell response and elevated levels of interleukin (IL)-12. We report our clinical experience with a novel oral IL-12/IL-23 inhibitor (STA 5326) for the treatment of active Crohn's disease. MATERIALS AND METHODS: We conducted an open-label, dose-escalating trial of the orally delivered small molecule immunomodulator STA 5326 in 73 patients with active Crohn's disease (Crohn's disease activity index [CDAI] 220-450, inclusive). Five cohorts of patients were treated for up to 4 weeks with 14 mg twice a day (bid), 35 mg daily (qd), 28 mg bid, 35 mg bid, or 70 mg qd. The endpoints of the study included safety and improvement in clinical activity measured by the CDAI and the Crohn's disease endoscopic index of severity. RESULTS: STA 5326 was well tolerated. Reported adverse events were similar across dose cohorts. The most common (>15%) drug-related adverse events observed were dizziness, nausea, headache, and fatigue. Clinical activity at day 28/29 was observed at qd doses of 28 mg and above for the clinical endpoints of response and remission: 70 points or greater decrease in CDAI (range 42%-82% of patients); 100 points or greater decrease in CDAI (range 38%-64% of patients), and CDAI <150 (range 15%-36%). CONCLUSIONS: Oral qd dosing of STA 5326 for 4 weeks was well tolerated in doses up to 70 mg qd in patients with active moderate to severe Crohn's disease. Clinical activity was observed at qd doses of 28 mg and above.

    AB - BACKGROUND: Intestinal inflammation associated with Crohn's disease is characterized by a type 1 helper T cell response and elevated levels of interleukin (IL)-12. We report our clinical experience with a novel oral IL-12/IL-23 inhibitor (STA 5326) for the treatment of active Crohn's disease. MATERIALS AND METHODS: We conducted an open-label, dose-escalating trial of the orally delivered small molecule immunomodulator STA 5326 in 73 patients with active Crohn's disease (Crohn's disease activity index [CDAI] 220-450, inclusive). Five cohorts of patients were treated for up to 4 weeks with 14 mg twice a day (bid), 35 mg daily (qd), 28 mg bid, 35 mg bid, or 70 mg qd. The endpoints of the study included safety and improvement in clinical activity measured by the CDAI and the Crohn's disease endoscopic index of severity. RESULTS: STA 5326 was well tolerated. Reported adverse events were similar across dose cohorts. The most common (>15%) drug-related adverse events observed were dizziness, nausea, headache, and fatigue. Clinical activity at day 28/29 was observed at qd doses of 28 mg and above for the clinical endpoints of response and remission: 70 points or greater decrease in CDAI (range 42%-82% of patients); 100 points or greater decrease in CDAI (range 38%-64% of patients), and CDAI <150 (range 15%-36%). CONCLUSIONS: Oral qd dosing of STA 5326 for 4 weeks was well tolerated in doses up to 70 mg qd in patients with active moderate to severe Crohn's disease. Clinical activity was observed at qd doses of 28 mg and above.

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