A Randomized Phase 2A, Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Safety and Effectiveness of Collagenase Clostridium Histolyticum in the Treatment of Dupuytren Disease Nodules: Level 1 Evidence

Abstract

Salary: Auxilium Pharmaceuticals Inc. (Kaufmann, James, Cohen), Ferring Pharmaceuticals (Kaufmann), US WorldMeds (James), Endo Pharmaceuticals Inc. (Cohen)Consulting Fee: Endo, BME, Biomet, Smith and Nephew (Gaston)▴This presentation will discuss Collagenase clostridium histolyticum. The objectives of this dose-ranging study were to assess the safety and effectiveness of CCH in treating palmar Dupuytren disease nodules. Nodules can cause significant pain and interference with patients’ activities of daily living (ADLs) involving gripping. Presently, there are no approved medical treatments for Dupuytren disease nodules. Subjects (n = 76) with Dupuytren disease and at least 1 palpable palmar nodule were randomized to receive a single injection of either CCH (0.60mg, 0.40mg, or 0.25mg) or placebo on Day 1. Nodules were massaged twice daily from Days 8 - 29. Nodule (size, consistency, hardness, pain, ultrasound measurements, and patient satisfaction) and safety assessments were conducted at specific time points throughout the study. Safety was monitored continuously. Surface area and volume of nodules assessed by calipers were significantly reduced (P = 0.0001) in CCH 0.6mg and 0.4mg groups compared to placebo group at Day 57. Significant improvements from baseline at endpoint were observed in consistency (0.6mg, P < 0.0001; 0.4mg, P = 0.0002; and 0.25mg, P = 0.0139) and hardness in CCH groups (0.6mg, P = 0.0075; 0.4mg, P < 0.0001; and 0.25mg, P = 0.0031) compared with the placebo group. 83.3% (15/18) and 88.9% (16/18) of subjects in CCH 0.60-mg group and CCH 0.40-mg group, respectively, were very satisfied or quite satisfied with treatment. Significantly higher percentage of composite responders (subject with an improved investigator assessment and a satisfied subject assessment) at Day 57 was observed in CCH 0.6mg group (77.8%; P = 0.0349) and 0.4mg group (88.9%; P = 0.0033) compared to placebo group (37.5%). Ultrasound findings were not statistically different between the CCH groups and placebo. Common adverse events in CCH subjects ( = 25.0%) were local swelling, injection bruising, axillary pain, contusion, pain in extremity; most were mild/moderate and resolved in 14 days (median). •CCH-treatment groups (0.60mg and 0.40mg) showed significant reduction in surface area and volume and softening of the treated nodule.•Subjective measures of investigator assessment of improvement and subject satisfaction with treatment were statistically significant.•Safety profile of single injection of CCH into a Dupuytren nodule was similar to that observed after single injection of CCH in treatment of adults with Dupuytren contracture with a palpable cord.