OA: cathepsin K inhibitor shows promise in European phase 2 trial

  • Conaghan PG & al.
  • Ann Intern Med
  • 31/12/2019

  • Miriam Davis, PhD
  • Clinical Essentials
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Takeaway

  • A European phase 2a trial of a novel inhibitor of cathepsin K, a protease that mediates bone resorption and cartilage degradation, found that reduced bone and cartilage thinning in osteoarthritis (OA), but not reduced pain, was the primary outcome.

Why this matters

  • This trial is among the first to study a disease-modifying drug (MIV-711), as none is on the market.

Study design

  • 26-week randomized, double-blind, placebo-controlled phase 2a trial at 6 European centers.
  • 244 participants with OA of Kellgren-Lawrence grade 2 or 3 and Numerical Rating Scale (NRS) for pain of 4-10 (scale 0-10).
  • 3 groups were tested: placebo, 100 mg daily group, and 200 mg daily group of the inhibitor.
  • Primary outcome: NRS pain reduction.
  • Bone and cartilage thinning were assessed by MRI.
  • Funding: Medivir.

Key results

  • NRS pain:
    • No significant change from baseline in all groups at 26 weeks.
  • Bone area:
    • The inhibitor groups showed reduced thinning, with significant difference vs placebo in least-squares means in the 100-mg group (P=.002) and the 200-mg group (P=.004).
  • Medial femoral joint cartilage:
    • 1 inhibitor group showed reduced thinning, with a significant difference vs placebo in least-squares mean in the 100-mg group (P=.023) but not the 200-mg group (P=.125).

Limitations

  • Short duration.