A Phase 1, Single-Blind, Randomized, Placebo-Controlled Dose Escalation Study to Assess Collagenase Clostridium Histolyticum (CCH) vs Placebo in Patients With Plantar Fasciitis (PFA)

Research Type: Level 1 - Randomized controlled trial (RCT), Meta-analysis of randomized trials with homogeneous results Introduction/Purpose: Improved nonsurgical treatment options are needed for PFA, the most common cause of heel pain. CCH is approved in the United States for the treatment of adults with Dupuytren’s contracture with a palpable cord and adult men with Peyronie’s disease with a palpable plaque and curvature deformity of at least 30°. A phase 1, randomized, dose-escalating study of CCH for PFA was conducted. Methods: Adults with painful, chronic PFA (duration >8 weeks; unresponsive after 6-12 months of conservative therapy) were eligible. Planned treatments included placebo and 3 CCH doses by intrafascial injection. Primary endpoints were the incidence, severity, and duration of treatment-emergent adverse events (TEAEs) through Day 84. Secondary endpoints included patient-reported measures of foot-related pain and treatment satisfaction. Outcomes were analyzed by comparing mean changes from baseline between treatment groups. Results: Sixty-two patients received placebo (n=14) or CCH treatment (n=48). Although the study was not powered to assess treatment efficacy, an improvement in mean pain scores was observed among CCH treatment groups from baseline to Day 84 (range, -4.0 to -4.3) vs placebo ( 2.8). A positive treatment satisfaction response was seen in 56.3%-66.7% of CCH patients compared to 35.7% of placebo patients. No treatment-related deaths or withdrawals occurred. Most TEAEs were mild to moderate in severity, resolving within 21 days. TEAEs were reported with a higher frequency and severity for the highest CCH dose. Most frequent TEAEs were similar to those seen in the approved indications: injection site pain, swelling, and bruising. Conclusion: Results warranted further evaluation in a phase 2, double-blind, placebo-controlled study (NCT06169319).