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 Contact: Name: Clinical Operations; Phone Number: 800-462-3636; Email: clinicaltrials@endo.com

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	Time Frame
Number of Participants with at Least 1-Level Lower Score for the Left Buttock (Investigational) Versus the Right Buttock (Control), as Assessed by the Investigator Assessment of Bruising Severity Scale (IABSS) After Initial CCH-aaes Injection	3 to 5 days after initial CCH-aaes injection on Day 1 (Cohorts 1 to 7) and Day 22 (Cohort 7 only)

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with at Least 1-Level Lower Score for the Left Buttock (Investigational) Versus the Right Buttock (Control), as Assessed by the IABSS After CCH-aaes Injection	Up to Day 64
Number of Participants with at Least +1 or Higher Score on the Investigator-Global Aesthetic Improvement Scale (I-GAIS) After CCH-aaes Injection	From Day 22 through Day 180
Number of Participants with Treatment-emergent Adverse Events	Up to Day 180
Number of Participants with Injection Site Reactions in the Left Buttock (Investigational) Versus the Right Buttock (Control)	Up to 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): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 27, 2023
• Last Verified: July 1, 2023

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