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

Joely Kaufman-Janette, John H Joseph, Michael S Kaminer, James Clark, Sabrina G Fabi, Michael H Gold, Mitchel P Goldman, Bruce E Katz, Kappa Peddy, Joel Schlessinger, V Leroy Young, Matthew Davis, David Hurley, Genzhou Liu, Michael P McLane, Saji Vijayan, Lawrence S Bass, Joely Kaufman-Janette, John H Joseph, Michael S Kaminer, James Clark, Sabrina G Fabi, Michael H Gold, Mitchel P Goldman, Bruce E Katz, Kappa Peddy, Joel Schlessinger, V Leroy Young, Matthew Davis, David Hurley, Genzhou Liu, Michael P McLane, Saji Vijayan, Lawrence S Bass

Abstract

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: ClinicalTrials.gov NCT03428750 NCT03446781.

Conflict of interest statement

J. H. Joseph is a shareholder and an investigator for Endo Pharmaceuticals Inc. J. Kaufman-Janette, M. S. Kaminer, M. H. Gold, B. E. Katz, J. Schlessinger, and V. Leroy Young are investigators and consultants for Endo Pharmaceuticals Inc. J. Clark and K. Peddy are also investigators for Endo Pharmaceuticals Inc. M. Davis, D. Hurley, G. Liu, M. P. McLane, and S. Vijayan are employees of Endo Pharmaceuticals Inc. L. S. Bass is an advisory board participant and consultant for Endo Pharmaceuticals Inc. S. G. Fabi and M. P. Goldman received research grants from Endo Pharmaceuticals Inc. V Leroy Young has also received registration and travel expenses from Endo Pharmaceuticals Inc.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society for Dermatologic Surgery.

Figures

Figure 1.
Figure 1.
Still shot from an injection technique video used to train study investigators. (To view the full video, please see the link in the article text.) The video demonstrates that the CCH injections are administered as three 0.1-mL aliquots, with 1 aliquot administered perpendicular to the skin and the other 2 aliquots administered at a 45-degree angle superior or inferior to the perpendicular axis. Reprinted with permission from Endo Pharmaceuticals Inc. 2020 All rights reserved.
Figure 2.
Figure 2.
Composite responders, defined as patients with ≥2-level or ≥1-level severity improvement from baseline in both CR-PCSS and PR-PCSS ratings at Day 71. CCH, collagenase clostridium histolyticum-aaes; CR-PCSS, Clinician Reported Photonumeric Cellulite Severity Scale; PR-PCSS, Patient Reported Photonumeric Cellulite Severity Scale; RELEASE, Randomized Evaluation of Cellulite Reduction by Collagenase Clostridium Histolyticum.
Figure 3.
Figure 3.
Photographs of composite response with CCH 0.84 mg compared with baseline. Baseline and Day 71 photographs demonstrate a 2-level improvement in both the CR-PCSS and PR-PCSS (A) and a 1-level improvement in both the CR-PCSS and PR-PCSS (B). CCH, collagenase clostridium histolyticum-aaes; CR-PCSS, Clinician Reported Photonumeric Cellulite Severity Scale; PR-PCSS, Patient Reported Photonumeric Cellulite Severity Scale. Reprinted with permission from Endo Pharmaceuticals Inc. © 2020 All rights reserved.
Figure 4.
Figure 4.
Frequency of responders for PR-PCSS and S-GAIS at Day 71 in the ITT population. CCH, collagenase clostridium histolyticum-aaes; ITT, intent-to-treat; PR-PCSS, Patient Reported Photonumeric Cellulite Severity Scale; RELEASE, Randomized Evaluation of Cellulite Reduction by Collagenase Clostridium Histolyticum; S-GAIS, Subject Global Aesthetic Improvement Scale.
Figure 5.
Figure 5.
Mean improvement from baseline in the PR-CIS total score at Day 71 in the mITT population. CCH, collagenase clostridium histolyticum-aaes; mITT, modified intent-to-treat; PR-CIS, Patient Reported Cellulite Impact Scale; RELEASE, Randomized Evaluation of Cellulite Reduction by Collagenase Clostridium Histolyticum. *Baseline values were used for women who did not have a Day 71 PR-CIS assessment.

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