Conference Coverage

Collagenase Clostridium Histolyticum Shows Promise in Alleviating Plantar Fasciitis: Phase 1 Study Supports Continued Investigation

Kate Young

Key Highlights:

  • Collagenase clostridium histolyticum (CCH) demonstrated clinically meaningful improvements in pain and function in patients with chronic plantar fasciitis through day 84.
  • All doses of CCH were associated with higher treatment satisfaction compared with placebo, with up to 66.7% of CCH-treated patients reporting themselves as responders.
  • The safety profile of CCH was consistent with previously approved indications, with most treatment-emergent adverse events (TEAEs) being mild to moderate and resolving within 21 days.
  • Study findings support further evaluation of CCH in a phase 2 double-blind, placebo-controlled trial, now underway.

A phase 1, single-blind, randomized, placebo-controlled, dose-escalation study assessed the safety, tolerability, immunogenicity, and early efficacy of collagenase clostridium histolyticum (CCH) in adults with chronic plantar fasciitis (PFA). The study found that all CCH dose groups showed improvements across multiple effectiveness measures through day 84, including pain intensity, foot pain severity and frequency, and patient-reported satisfaction. Improvements in pain scores were more pronounced in the CCH groups versus placebo, suggesting a potential therapeutic benefit of CCH in this population. This study was presented at the American Podiatric Medical Association 2025 Annual Scientific Meeting, in Dallas/Forth Worth, TX.

Chronic plantar fasciitis is the most common cause of heel pain, often resistant to conservative treatments, and significantly affects quality of life. Histologic studies suggest a degenerative process in the collagen matrix of the plantar fascia, indicating a role for collagen-targeting therapies. CCH, a biologic agent approved for Dupuytren’s contracture and Peyronie’s disease, enzymatically disrupts collagen and may be a novel treatment option for PFA.

This phase 1 multicenter study enrolled 62 patients randomized into placebo or escalating CCH dose groups (~0.20 mg, 0.34 mg, and 0.60 mg). Patients received one treatment session of three intrafascial injections, followed through day 84. Effectiveness assessments included the Pain Intensity Numeric Rating Scale (NRS), Foot Pain Severity and Frequency scales, and patient satisfaction. Safety was monitored by the incidence and severity of TEAEs, while immunogenicity was evaluated via anti-AUX-I and -II antibody titers.

Patients treated with CCH exhibited dose-dependent improvements across all clinical measures. By day 84, NRS pain scores improved by 4.1 to 4.3 points in CCH groups versus 2.8 in placebo. Similarly, greater improvements were observed in the CCH arms for foot pain interference (1.4–1.7 vs 1.0) and frequency (1.3–1.9 vs 1.3). Satisfaction with treatment was higher among CCH recipients, with 56.3%–66.7% meeting responder criteria, compared to 35.7% of placebo patients. Most TEAEs were mild to moderate and related to injection site reactions. Higher dose groups experienced more frequent and longer-lasting TEAEs, but no serious adverse events occurred.

“Results warrant further evaluation in a phase 2 double-blinded, placebo-controlled study, which is ongoing,” the study authors concluded.

Reference:
Caporusso J, Gottlieb I, Levy J, et al. A phase 1, single-blind, randomized, placebo-controlled dose escalation study to assess CCH vs placebo in patients with plantar fasciitis. Presented at: American Podiatric Medical Association (APMA) Annual Scientific Meeting; July 24-27, 2025; Dallas/Fort Worth, TX. https://www.apma.org/the-national/