Tolerability and Safety of Collagenase Clostridium Histolyticum Injection in Participants with Plantar Fibromatosis

Abstract

Category: Midfoot/Forefoot; Basic Sciences/Biologics Introduction/Purpose: Plantar fibromatosis (PFi) is a functionally disabling disorder characterized by fibrous collagen-containing nodules along the plantar fascia. Collagenase clostridium histolyticum (CCH) is a nonsurgical treatment approved for Dupuytren’s and Peyronie’s disease; both can coexist with PFi. Composed of two collagenases, CCH specifically hydrolyzes certain collagen types and may disrupt the nodule when injected directly. This proof-of-concept study evaluated pharmacokinetics, immunogenicity, and assessed tolerability and safety of CCH treatment of PFi. Methods: In this Phase 1, multicenter study, participants were randomly allocated (1:1:1) to receive 0.6, 1.2, or 2.25 mg/mL CCH. All participants underwent the initial treatment period (ITP) and received 1–2 intralesional injections per nodule on Day 1 with pharmacokinetic samples collected over 24hrs, followed by 5 follow-up visits. Post-ITP, participants with a remaining, palpable nodule could enter the retreatment period (RP) and receive additional CCH doses (at 2.25 mg/mL) with follow-up at specified intervals. Immunogenicity test sampling occurred at screening and at the end of ITP/RP. Adverse events (AEs) were monitored throughout. Results: Twenty-four participants enrolled into ITP, with 11 continuing into RP. Pharmacokinetic and immunogenicity findings were consistent with previous CCH studies in other therapeutic areas. CCH treatment was generally well tolerated, with no serious treatment emergent adverse events (TEAEs), drug discontinuations, or study withdrawals by study end. Over 70% of participants during ITP (19/24) and RP (8/11) reported at least 1 TEAE. Eighty-six TEAEs occurred during ITP and 35 in RP; most were mild in severity (73%, ITP; 83%, RP), and 67% of ITP and 49% of RP TEAEs were treatment related. TEAEs were reportedly injection site- related, with injection site bruising, pain, and swelling frequently recorded. Conclusion: CCH had an expected pharmacokinetics/immunogenicity profile and was safe and well tolerated in participants with PFi. CCH may be a potential nonsurgical intralesional option for PFi treatment.