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Abstract Number: 1760

A Phase 2 Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of a Mitogen-activated Protein Kinase-Activated Protein Kinase 2 (MK2) Inhibitor in Active Ankylosing Spondylitis

Walter Maksymowych1, Robert Lambert1, Paula Śliwinska-Stańczyk2, Piotr Adrian Klimiuk3, Anusha Yeshokumar4, Elizabeth Cerullo4, Rebecca Kepich4, Chahin Pachai4 and Steven Greenberg4, 1University of Alberta, Edmonton, AB, Canada, 2Centrum Medyczne ReumaPark, Warsaw, Poland, 3Medical University of Bialystok and Inter Clinic Piotr Adrian Klimiuk, Department of Rheumatology and Internal Diseases, Białystok, Poland, 4Bristol Myers Squibb, Princeton, NJ

Meeting: ACR Convergence 2024

Keywords: Ankylosing spondylitis (AS), clinical trial, Spondyloarthropathies

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Session Information

Date: Sunday, November 17, 2024

Title: Abstracts: SpA Including PsA – Treatment I

Session Type: Abstract Session

Session Time: 3:00PM-4:30PM

Background/Purpose: CC-99677 (also known as BMS-986371) is a novel, orally bioavailable, small-molecule covalent inhibitor of mitogen-activated protein (MAP) kinase-activated protein kinase 2 (MK2). The MK2 enzyme is regulated through direct phosphorylation by p38 MAP kinase and it enhances stabilization and translation of mRNA of proinflammatory cytokines, such as TNF-α, IL-17 and IL-6. This is accomplished by phosphorylation and inhibition of the mRNA destabilizing function of tristetraprolin, which leads to cytokine translation. CC-99677 is a potent and selective covalent inhibitor of MK2 in biochemical and cellular assays. We aimed to evaluate the dose-dependent efficacy of oral CC-99677 compared to placebo in subjects with ankylosing spondylitis (AS) and inadequate response to NSAIDs.

Methods: This was a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group, efficacy and safety study to assess response to CC-99677 treatment by measuring signs and symptoms of ankylosing spondylitis, objective measures of disease activity, quality of life assessments, safety, and tolerability over a 12-week double-blind period. This study also aimed to assess the efficacy and long-term safety of CC-99677 in a 52-Week Long-term Extension Period. Patients were randomized 1:1:1 to CC-99677 150 mg PO QD, CC-99677 60 mg PO QD, or matching placebo, stratified by screening hsCRP concentration (≤ or >5.0mg/L). Main inclusion criteria were a diagnosis of AS, fulfilment of the modified New York criteria for AS, active symptoms (BADSDAI >4 and Total Back Pain (TBP) >4) despite ≥2 NSAID, and naïve to bioDMARD in the main study. A total of 147 subjects were planned to be randomized, 49 subjects to each treatment group, for 80% power to detect a 25% difference in ASAS20 response at Week 12, the primary endpoint, between either active treatment group and placebo. The Hochberg procedure was applied to the analysis to adjust for multiplicity. A substudy planned recruitment up to 50 patients that were bioDMARD-inadequate responders (IR).

Results: We present results only for the biologic-naïve main study. 147 subjects were enrolled: 49 in CC-99677 60 mg group, 49 in CC-99677 150 mg group, 49 subjects in placebo. A total of 123 (83.7%) subjects completed treatment in the double-blind, 12-week placebo-controlled period and 24 (16.3%) subjects discontinued treatment. The main reason for discontinuation was study termination by Sponsor Steering Committee after interim analysis when approximately 50 subjects in the biologic-naïve main study completed 12 weeks of treatment. Baseline characteristics were typical of an AS trial population (Table 1). Treatment with CC-99677 was generally safe and well-tolerated (Table 2). For efficacy, ASAS20 and ASAS 40 at Week 12 was 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 group differences were noted for key secondary endpoints at week 12 (ASDAS, BASDAI, BASFI, SPARCC MRI SIJ and spine scores) (Table 3).

Conclusion: The study was prematurely terminated for futility. The termination was not related to any observed adverse events, or perceived safety findings associated with CC-99677.

Supporting image 1

Table 1. Patient Demographics and Disease Characteristics (bioDMARD naïve)

Supporting image 2

Table 2. Safety Overview to Week 12 (bioDMARD naïve)

Supporting image 3

Table 3. Efficacy Outcomes to Week 12 (bioDMARD naïve)


Disclosures: W. Maksymowych: AbbVie, 2, 5, 6, Boehringer Ingelheim, 2, 6, Bristol Myers Squibb (BMS), 2, 6, CARE Arthritis Limited, 4, Celgene, 2, 6, Eli Lilly, 2, 6, Galapagos, 2, 5, 6, Janssen, 2, 5, 6, Novartis, 2, 5, 6, Pfizer, 2, 5, 6, UCB Pharma, 2, 5, 6; R. Lambert: CARE Arthritis, 2, Image Analysis Group, 2; P. Śliwinska-Stańczyk: None; P. Klimiuk: None; A. Yeshokumar: Bristol-Myers Squibb(BMS), 3; E. Cerullo: Bristol-Myers Squibb(BMS), 3; R. Kepich: Bristol-Myers Squibb(BMS), 3; C. Pachai: Bristol-Myers Squibb(BMS), 3; S. Greenberg: Bristol-Myers Squibb(BMS), 3.

To cite this abstract in AMA style:

Maksymowych W, Lambert R, Śliwinska-Stańczyk P, Klimiuk P, Yeshokumar A, Cerullo E, Kepich R, Pachai C, Greenberg S. A Phase 2 Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of a Mitogen-activated Protein Kinase-Activated Protein Kinase 2 (MK2) Inhibitor in Active Ankylosing Spondylitis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/a-phase-2-multicenter-randomized-double-blinded-placebo-controlled-parallel-group-study-to-evaluate-the-efficacy-and-safety-of-a-mitogen-activated-protein-kinase-activated-protein-kinase-2-mk2-i/. Accessed .
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All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

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