{
  "abstract": "Background/Purpose CC-99677 (BMS-986371) is a novel, small-molecule covalent inhibitor of mitogen-activated protein kinase-activated protein kinase 2 (MK2). We aimed to evaluate the dose-dependent efficacy and safety of CC-99677 compared with placebo in subjects with ankylosing spondylitis (AS).Methods This was a phase II, multicentre, randomised, double-blind, placebo-controlled trial to assess the efficacy and safety of CC-99677 in subjects with AS. Subjects were randomised 1:1:1 to once-daily CC-99677 150 mg, CC-99677 60 mg or placebo. Main inclusion criteria were fulfilment of the modified New York criteria for AS, active symptoms (Bath Ankylosing Spondylitis Disease Activity Index ≥4 and total back pain ≥4) despite ≥2 non-steroidal anti-inflammatory drugs and naïve to biologic disease-modifying anti-inflammatory drugs. The primary end point was Assessment of SpondyloArthritis international Society 20% improvement criteria (ASAS20) response at 12 weeks.Results 147 subjects were enrolled and 123 (83.7%) subjects completed treatment in the double-blind, placebo-controlled period. The main reason for discontinuation was study termination based on futility at interim analysis. Baseline characteristics were typical of an AS trial population. Treatment with CC-99677 was generally well-tolerated. ASAS20 and ASAS40 at week 12 were 51.2% and 25.6% in the CC-99677 60 mg group, 56.1% and 34.1% in the 150 mg group and 48.8% and 22.0% in the placebo group. No significant treatment group differences were noted for secondary end points. There were trends in active treatment groups for improvement in MRI spine and sacroiliac joint inflammation scores but minimal inhibition of pro-inflammatory cytokines in serum.Conclusions Inhibition of MK2 by CC-99677 was insufficient to lead to significant clinical benefits in AS.Trial registration number NCT04947579.",
  "authors": [
    {
      "affiliations": [
        "Department of Medicine, University of Alberta, Edmonton, Alberta, Canada",
        "CARE Arthritis Limited, Edmonton, Alberta, Canada"
      ],
      "name": "Walter P Maksymowych"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, New Jersey, USA"
      ],
      "name": "Anusha Yeshokumar"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, New Jersey, USA"
      ],
      "name": "Elizabeth Cerullo"
    },
    {
      "affiliations": [
        "Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada"
      ],
      "name": "Robert G W Lambert"
    },
    {
      "affiliations": [
        "Centrum Medyczne ReumaPark, Warsaw, Poland"
      ],
      "name": "Paula Śliwinska-Stańczyk"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Internal Diseases, Medical University of Bialystok, Bialystok, Poland",
        "Inter Clinic Piotr Adrian Klimiuk, Bialystok, Poland"
      ],
      "name": "Piotr Klimiuk"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, New Jersey, USA"
      ],
      "name": "Rebecca Kepich"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, New Jersey, USA"
      ],
      "name": "Chahin Pachai"
    },
    {
      "affiliations": [
        "AstraZeneca, Bensalem, Pennsylvania, USA"
      ],
      "name": "Min Zhu"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, New Jersey, USA"
      ],
      "name": "Jinqi Liu"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, New Jersey, USA"
      ],
      "name": "Jessica Landis"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, New Jersey, USA"
      ],
      "name": "Vineet Goti"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, New Jersey, USA"
      ],
      "name": "Steven Greenberg"
    }
  ],
  "title": "Phase II randomised, placebo-controlled study to evaluate the efficacy and safety of an MK2 inhibitor in ankylosing spondylitis",
  "uid": "247396d0-6c81-562f-b6bf-52395bc32dd0"
}