Collagenase Clostridium Histolyticum-aaes for the Treatment of Cellulite in Women: Results From Two Phase 3 Randomized, Placebo-Controlled Trials

Dermatol Surg. 2021 May 1;47(5):649-656. doi: 10.1097/DSS.0000000000002952.


Background: Fibrous septae play a role in contour alterations associated with cellulite.

Objective: To assess collagenase clostridium histolyticum-aaes (CCH) for the treatment of cellulite.

Materials and methods: Two identically designed phase 3, double-blind, randomized studies (RELEASE-1 and RELEASE-2) were conducted. Adult women with moderate/severe cellulite (rating 3-4 on the Patient Reported Photonumeric Cellulite Severity Scale [PR-PCSS] and Clinician Reported PCSS [CR-PCSS]) on the buttocks received up to 3 treatment sessions of subcutaneous CCH 0.84 mg or placebo per treatment area. Composite response (≥2-level or ≥1-level improvement from baseline in both PR-PCSS and CR-PCSS) was determined at Day 71.

Results: Eight hundred forty-three women received ≥1 injection (CCH vs placebo: RELEASE-1, n = 210 vs n = 213; RELEASE-2, n = 214 vs n = 206). Greater percentages of CCH-treated women were ≥2-level composite responders versus placebo in RELEASE-1 (7.6% vs 1.9%; p = .006) and RELEASE-2 (5.6% vs 0.5%; p = .002) and ≥1-level composite responders in RELEASE-1 (37.1% vs 17.8%; p < .001) and RELEASE-2 (41.6% vs 11.2%; p < .001). Most adverse events (AEs) in the CCH group were injection site related; few CCH-treated women discontinued because of an AE (≤4.3%).

Conclusion: Collagenase clostridium histolyticum-aaes significantly improved cellulite appearance and was generally well tolerated.

Trial registration: NCT03428750 NCT03446781.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Neutralizing / blood
  • Cellulite / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Injection Site Reaction / etiology
  • Microbial Collagenase / adverse effects
  • Microbial Collagenase / immunology
  • Microbial Collagenase / therapeutic use*
  • Middle Aged
  • Patient Satisfaction
  • Treatment Outcome


  • Antibodies, Neutralizing
  • Microbial Collagenase

Associated data