A Phase 2, Double-blind, Randomized, Placebo-Controlled Study to Assess Collagenase Clostridium Histolyticum vs Placebo in Patients With Plantar Fibromatosis

• Published in: Foot & ankle orthopaedics 2024-12, Vol.9 (4)
• Main Authors: James Anderson, C., Gottlieb, Ira, Levy, Jason, El-Amin, Saadiq, Suttle, Sara, Tursi, James, Jones, Nigel, Ortega, Luis A., Zhou, Gongfu, Caporusso, Joseph
• Format: Article
• Language: English
• Subjects: Connective tissue diseases; Pain
• ISSN: 2473-0114; 2473-0114
• DOI: 10.1177/2473011424S00116

Category: Midfoot/Forefoot; Basic Sciences/Biologics Introduction/Purpose: Collagenase clostridium histolyticum (CCH), a nonsurgical treatment approved for Peyronie’s disease and Dupuytren’s contracture, is being investigated for plantar fibromatosis (PFI), or Ledderhose disease, a rare disorder characterized by benign, slow-growing, collagen-containing nodules along the foot’s medial or central plantar fascia. Here, we report on safety and efficacy results of a multicenter phase 2b randomized, placebo-controlled trial (NCT05152173). Methods: Multicenter patients with PFI, at least one “moderately firm” to “hard” nodule causing pain were randomized 1:1 to CCH treatment or placebo. The primary endpoint was mean change in pain from baseline to Day 57 via the Foot Function Index (FFI)-Pain subscale. Secondary outcomes included the Clinical Global Impression of Change (CGIC) scale and changes in nodule hardness (by durometer) and consistency (firmness by palpation). Outcomes were analyzed by ANCOVA and MMRM from baseline to Day 57. Results: A total of 166 subjects (83 CCH, 83 placebo) completed the study. At Day 57, the mean FFI-Total subscale Pain score trended toward improvement in both groups; however, the difference was not statistically significant (Figure-1a) (least squares mean [LSM] difference, -1.427; 95% CI -3.985 to 1.131; P=0.274). The CGIC showed there were 14.8% more responders in the CCH group vs placebo (P=0.044). Also, statistically significant improvements occurred in nodule hardness (Figure-1b) (LSM difference, -5.877; P=0.020) and consistency (22.4% more responders; P=0.002) between the CCH group and placebo, favoring CCH treatment. Similar to other approved CCH indications, common treatment-related or -emergent adverse events (AEs) were injection site pain, bruising, and swelling. There were no deaths, serious AEs, or study withdrawals in the CCH treatment group. Conclusion: As this trial demonstrated a trend in treatment effect for the primary endpoint with some secondary endpoints illustrating a significant treatment benefit versus placebo, an appropriately powered pivotal phase 3 trial is underway. Figure 1. Mean Change From Baseline to Day 57 on FFI-Total Pain Subscale Score (a) and Nodular Hardness by Durometer (b).