Study of Different Interventions to Reduce Bruising Following CCH-Aaes Treatment for Cellulite of the Buttocks (APHRODITE)

APHRODITE-1: A Phase 2, Open Label, Self-Controlled Study of Different Interventions to Reduce Bruising Following CCH-Aaes Treatment for Cellulite of the Buttocks in Adult Females

The study will evaluate the effect of different doses, strengths (concentrations), diluent additives, depths of injection, and methods of injection on the severity of bruising potentially induced by QWO (collagenase clostridium histolyticum-aaes [CCH-aaes]).

Study Overview

• Status: Completed
• Conditions: Cellulite; Edematous Fibrosclerotic Panniculopathy
• Intervention / Treatment: Drug: CCH-aaes; Drug: Antifibrinolytic Agent

Detailed Description

The study will comprise a Screening Period (28 days), Treatment Period (90 days), and Follow-up Period (90 days). Participants will receive CCH-aaes in different doses, concentrations, diluent additives, depths of injection, and methods of injection in a split buttock arrangement, with the right buttock serving as the control, and the left buttock (investigational side) receiving a study intervention.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85255
      • Endo Clinical Trial Site #6
  • California
    • Beverly Hills, California, United States, 90210
      • Endo Clinical Trial Site #4
    • Encinitas, California, United States, 92024
      • Endo Clinical Trial Site #9
    • San Diego, California, United States, 92121
      • Endo Clinical Trial Site #10
    • Solana Beach, California, United States, 92075
      • Endo Clinical Trial Site #7
  • Colorado
    • Greenwood Village, Colorado, United States, 80111
      • Endo Clinical Trial Site #12
  • Florida
    • Coral Gables, Florida, United States, 33146
      • Endo Clinical Trial Site #8
    • Miami, Florida, United States, 33137
      • Endo Clinical Trial Site #13
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Endo Clinical Trial Site #3
  • Louisiana
    • Metairie, Louisiana, United States, 700006
      • Endo Clinical Trial Site #2
  • New York
    • New York, New York, United States, 10021
      • Endo Clinical Trial Site #11
  • Tennessee
    • Nashville, Tennessee, United States, 37215
      • Endo Clinical Trial Site #1
  • Texas
    • Pflugerville, Texas, United States, 78660
      • Endo Clinical Trial Site #5

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Have a body mass index of 18 to <32 kilograms (kg)/meter (m)^2 and intends to maintain stable body weight during the study.
• Have both buttocks with moderate or severe cellulite as reported by the investigator using the Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS).
• Have a Hexsel Cellulite Severity Scale (CSS) Total Score of ≤12.
• Has a Fitzpatrick Skin Type of I-IV
• Be willing to apply sunscreen to the treatment areas before each exposure to the sun for the duration of participation in the study.
• Be willing and able to comply with the requirements of the study.

Key Exclusion Criteria:

• Has systemic conditions (coagulation disorders, skin pigmentation disorders, malignancy, keloidal scarring, abnormal wound healing) that restricts study participation.
• Is pregnant and/or is breast-feeding or plans to become pregnant and/or to breast-feed during the course of the study.
• Has any local (in the areas to be treated) conditions (thrombosis, post-thrombosis syndrome, vascular disorder, inflammation, active infection, active cutaneous alteration, tattoo or mole) that restricts study participation.
• Requires antiplatelet medication, anticoagulants, or non-steroidal anti-inflammatory drugs during the study.
• Any medications, supplements, or foods that have, or have been reported to have anticoagulant effects within 14 days of treatment.
• Has received treatment with investigational treatment within 30 days before treatment.
• Has used or intends to use any of the local applications, therapies, injections, or procedures for the treatment of cellulite on either buttock that would restrict study participation.
• Intends to initiate an intensive sport or exercise program or intensive weight reduction program during the study.
• Intends to engage in strenuous activity within 48 hours of study intervention administration.
• Has recently tanned or intends to tan (outdoors or indoors) during the study.
• Has a history of hypersensitivity or allergy to collagenase or any other excipient of CCH.
• Has any condition(s) that, in the investigator's opinion, might indicate the participant to be unsuitable for the study.
• Has participated in a previous investigational study of CCH or received any collagenase treatments at any time prior to treatment in this study for the treatment of cellulite of the buttocks.

In addition to the applicable aforementioned exclusion criteria, participants enrolling in Cohort 7 will be excluded from study participation if the participant:

• Has any of the following medical conditions:

  1. history of venous or arterial thromboembolism or current thromboembolic disease.
  2. history of or current renal impairment.
  3. serum creatinine concentration > 1.4 milligram/deciliter at Screening.

• Requires the following concomitant medications during the study and cannot discontinue these medications within the time specified before CCH-aaes treatment:

  1. concurrently taking combination hormonal contraceptives.
  2. concurrently undergoing hormone replacement therapy.
  3. is a current smoker of nicotine or cannabinoids.
• Participants in Cohort 7 should avoid smoking (including vaping, nicotine, or marijuana cigarettes) during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: CCH-aaes Dose Evaluation; Participants will be administered CCH-aaes at different doses. Participants will receive CCH-aaes treatments in a split buttock arrangement, with the right buttock as the control, and the left buttock as the investigational treatment.	Drug: CCH-aaes; Administered by subcutaneous injection.; Other Names: Collagenase clostridium histolyticum-aaes; QWO®
Experimental: Cohort 2: CCH-aaes Concentration Evaluation; Participants will be administered CCH-aaes at different concentrations. Participants will receive CCH-aaes treatments in a split buttock arrangement, with the right buttock as the control, and the left buttock as the investigational treatment.	Drug: CCH-aaes; Administered by subcutaneous injection.; Other Names: Collagenase clostridium histolyticum-aaes; QWO®
Experimental: Cohort 3: CCH-aaes Injection Depth Evaluation; Participants will be administered CCH-aaes using different injection depths. Participants will receive CCH-aaes treatments in a split buttock arrangement, with the right buttock as the control, and the left buttock as the investigational treatment.	Drug: CCH-aaes; Administered by subcutaneous injection.; Other Names: Collagenase clostridium histolyticum-aaes; QWO®
Experimental: Cohort 4: CCH-aaes Injection Method Evaluation; Participants will be administered CCH-aaes using different injection methods. Participants will receive CCH-aaes treatments in a split buttock arrangement, with the right buttock as the control, and the left buttock as the investigational treatment.	Drug: CCH-aaes; Administered by subcutaneous injection.; Other Names: Collagenase clostridium histolyticum-aaes; QWO®
Experimental: Cohort 5: CCH-aaes and Diluent Additive Evaluation; Participants will be administered CCH-aaes and diluent additive. Participants will receive CCH-aaes treatments in a split buttock arrangement, with the right buttock as the control, and the left buttock as the investigational treatment.	Drug: CCH-aaes; Administered by subcutaneous injection.; Other Names: Collagenase clostridium histolyticum-aaes; QWO®
Experimental: Cohort 6: CCH-aaes Dose, Concentration, and Treatment Schedule Evaluation; Participants will be administered CCH-aaes using a different treatment schedule and different doses and concentrations. Participants will receive CCH-aaes treatments in a split buttock arrangement, with the right buttock as the control, and the left buttock as the investigational treatment.	Drug: CCH-aaes; Administered by subcutaneous injection.; Other Names: Collagenase clostridium histolyticum-aaes; QWO®
Experimental: Cohort 7: CCH-aaes and Antifibrinolytic Agent; Participants will be administered CCH-aaes and an antifibrinolytic agent. Participants will receive CCH-aaes treatments in a split buttock arrangement, with the right buttock as the control, and the left buttock as the investigational treatment.	Drug: CCH-aaes; Administered by subcutaneous injection.; Other Names: Collagenase clostridium histolyticum-aaes; QWO®; Drug: Antifibrinolytic Agent; Self-administered by participants enrolled in Cohort 7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least 1-Level Lower Score 3 to 5 Days After Initial CCH-aaes Injection, as Assessed by the Investigator Assessment of Bruising Severity Scale (IABSS) After Initial CCH-aaes Injection	The investigator assessed the severity of bruising using the IABSS, The IABSS is a 5-point scale ranging from 0-4, with 0 indicating no bruising or almost none, and 4 indicating very severe bruising. Higher scores indicated worse outcomes. The investigator compared the bruising of the left (test) buttock to the right (control) buttock. Responders were participants whose left buttock/test side demonstrated at least a 1-level lower IABSS score versus the right buttock/control side. Percentages are based on the number of participants with an assessment at specified timepoint.	3 to 5 days after initial CCH-aaes injection of left buttock (test) and right buttock (control)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least 1-Level Lower Score, as Assessed by the IABSS	The investigator assessed the severity of bruising using the IABSS, The IABSS is a 5-point scale ranging from 0-4, with 0 indicating no bruising or almost none, and 4 indicating very severe bruising. Higher scores indicated worse outcome. The investigator compared the bruising of the left buttock (test) to the right (control) buttock. Responders were participants whose left buttock/test side at Visit A demonstrated at least a 1-level lower IABSS score versus the right buttock/control side at Visit B, where Visit A and B could either be the same or different. Follow-up after first injection is presented: Follow-up 1 is 1 to 2 days after injection visit, Follow-up 2 is 3 to 5 days after injection visit, Follow-up 3 is 6 to 9 days after injection visit, and Follow-up 4 is 10 to 14 days after injection visit. Percentages are based on the number of participants with an assessment at specified timepoint.	Follow-up 1, 2, 3, and 4 after CCH-aaes injection of left buttock (test) and right buttock (control)
Percentage of Participants With at Least +1 or Higher Score on the Investigator-Global Aesthetic Improvement Scale (I-GAIS) After CCH-aaes Injection	The investigator determined the degree of improvement of each buttock by comparing treated cellulite dimples from the Day 1 pre-treatment (Baseline) digital image of each buttock to the treated dimples observed in a live assessment. The investigator determined the degree of improvement of each buttock with the I-GAIS, which uses a 7-point scale ranging from +3 (very much improved) to -3 (very much worse). A higher score indicated a better outcome. The investigator compared the bruising of the left (test) buttock to the right (control) buttock. A 1-level I-GAIS responder was defined as any participant with an improved (+1, +2 or +3) score on the I-GAIS at an analysis visit for that treatment area. Percentages are based on the number of participants with an assessment at specified timepoint.	Day 22 and Day 43 for Cohorts 1 to 5, Day 43 for Cohort 6, Day 22, Day 43, and Day 64 for Cohort 7, and Day 90, Day 135, and Day 180 for all cohorts
Percentage of Participants With Injection Site Reactions	Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) that occur or worsen (increase in severity) on the same day or after the study intervention administration on Day 1. Percent of participants with TEAEs of injection site reactions are presented by left buttock (test) and right buttock (control). A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.	From Day 1 (after dose) through Day 180

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals
• Investigators: Study Director: David Hernandez, Endo Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2022
• Primary Completion (Actual): January 3, 2023
• Study Completion (Actual): June 21, 2023

Study Registration Dates

• First Submitted: June 9, 2022
• First Submitted That Met QC Criteria: June 10, 2022
• First Posted (Actual): June 15, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 4, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Collagenase Clostridium Histolyticum; collagenase clostridium histolyticum-aaes
• Additional Relevant MeSH Terms: Skin Manifestations; Cellulite; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Hemostatics; Coagulants; Antifibrinolytic Agents
• Other Study ID Numbers: EN3835-226

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No