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Category: Midfoot/Forefoot; Basic Sciences/Biologics Introduction/Purpose: Plantar fibromatosis (PFi) is characterized by collagen-containing nodules on the foot along the plantar fascia that can cause pain and functional disability. Current treatments focus on symptom relief, which may become ineffective, or surgery, which can have lengthy recovery times. Collagenase clostridium histolyticum (CCH) is approved for Dupuytren’s and Peyronie’s disease treatment, which are both fibroproliferative disorders that may coexist in patients with PFi. This dose-ranging study assessed the efficacy 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 5 follow-up assessments. Participants with palpable treated nodules could receive additional CCH doses (at 2.25 mg/mL; retreatment period, RP), with follow-up at specified intervals. Assessments included a 5-scale measure of nodule hardness (0 [nonpalpable] to 4 [hard]), and the Foot Function Index-Short Form23 (FFI-SF23) reported as a composite score (0 – 100) of 3 subscale scores (disability, difficulty, and pain subscales). Results: After ITP (n=24), 100% (8/8) of participants receiving 2.25 mg/mL CCH showed improvement in nodule hardness, compared with 87.5% (7/8) and 75% (6/8) of participants receiving 1.2 and 0.6 mg/mL, respectively. FFI-SF23 also showed a negative change from baseline across treatment groups, indicating improvement. Participants that received 2.25 mg/mL reported the largest percent improvement (-83.7%). After RP (n=11), 81.8% (9/11) of participants showed improvement in nodular hardness and an FFI-SF23 score change of -9.3%, indicating further improvement from baseline after ITP. CCH had a consistent safety profile in ITP/RP. Conclusion: CCH caused dose-dependent improvement of nodule hardness after treatment, with 2.25 mg/mL utilized for nodule retreatment; FFI-SF23 scores correlated with this finding, indicating CCH may be a potential nonsurgical intralesional option for PFi treatment.

Category: Midfoot/Forefoot; Basic Sciences/Biologics Introduction/Purpose: Currently, there is no safe and efficacious injectable therapy for symptomatic plantar fibromatosis (PFi) that addresses its pathophysiology. Patients with PFi nodules experience symptoms that reduce quality of life, causing functional disability leading to severe impairment in some patients. Collagenase clostridium histolyticum (CCH) is approved for Dupuytren’s and Peyronie’s disease treatment, which are both fibroproliferative disorders that may coexist in patients with PFi. This first study of CCH treatment for PFi evaluated participant satisfaction and investigator assessment of improvement. Methods: Participants were randomly allocated (1:1:1) in this Phase 1, multicenter study 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 follow-up assessments at specified intervals. Participants with palpable treated nodules could enter the retreatment period (RP) and receive additional CCH doses (at 2.25 mg/mL), with follow-up at specified intervals. Assessments included the Subject Satisfaction with Treatment Rating Scale (+2: very satisfied; to -2: very dissatisfied), and the Investigator Assessment of Improvement Scale (+3: very much improvement; to -3: very much worse). Results: After ITP, ≥75% of participants reported “very” or “quite” satisfied across all treatment groups, with 2.25 mg/mL group reporting 100% satisfaction. For ≥72.7% of nodules, participants reported satisfaction with outcome. Investigators reported improvement (“minimal”, “much”, or “very much”) in ≥75% of participants and ≥80% of treated nodules. After RP, 63.6% of participants reported treatment satisfaction; participants were satisfied with 66.7% of treated nodules, indicating continued improvement from the ITP. Almost all participants (90.9%) were deemed by investigators to have shown improvement, with 86.7% of treated nodules being assessed as having improvement. Conclusion: CCH-treated PFi participants were satisfied with their improvement; physicians assessed improvement in >90% of participants. Results indicate CCH as a potential nonsurgical intralesional option for PFi treatment.

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.