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

• ClinicalTrials.gov Identifier: NCT05419505
• Recruitment Status: Active, not recruiting
• First Posted: June 15, 2022
• Last Update Posted: January 19, 2023
• Sponsor: Endo Pharmaceuticals
• Information provided by (Responsible Party): Endo Pharmaceuticals

Tracking Information

• First Submitted Date: June 9, 2022
• First Posted Date: June 15, 2022
• Last Update Posted Date: January 19, 2023
• Actual Study Start Date: June 15, 2022
• Actual Primary Completion Date: January 3, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 28, 2022): 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 [ Time Frame: 3 to 5 days after initial CCH-aaes injection on Day 1 (Cohorts 1 to 7) and Day 22 (Cohort 7 only) ]
• Original Primary Outcome Measures (submitted: June 10, 2022): 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 [ Time Frame: 3 to 5 days after initial CCH-aaes injection on Day 1 ]

Current Secondary Outcome Measures (submitted: November 28, 2022)

• 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 [ Time Frame: 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 [ Time Frame: From Day 22 through Day 180 ]
• Number of Participants with Treatment-emergent Adverse Events [ Time Frame: Up to Day 180 ]
• Number of Participants with Injection Site Reactions in the Left Buttock (Investigational) Versus the Right Buttock (Control) [ Time Frame: Up to Day 180 ]

Original Secondary Outcome Measures (submitted: June 10, 2022)

• 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 [ Time Frame: Up to Day 57 ]
• Number of Participants with at Least +1 or Higher Score on the Investigator-Global Aesthetic Improvement Scale (I-GAIS) After CCH-aaes Injection [ Time Frame: From Day 22 through Day 180 ]
• Number of Participants with Treatment-emergent Adverse Events [ Time Frame: Up to Day 180 ]
• Number of Participants with Injection Site Reactions in the Left Buttock (Investigational) Versus the Right Buttock (Control) [ Time Frame: Up to Day 180 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Different Interventions to Reduce Bruising Following CCH-Aaes Treatment for Cellulite of the Buttocks
• Official Title: 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
• Brief Summary: 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]).
• 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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Edematous Fibrosclerotic Panniculopathy
• Cellulite

Intervention

• 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.

Study Arms

• 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.
  Intervention: Drug: CCH-aaes
• 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.
  Intervention: Drug: CCH-aaes
• 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.
  Intervention: Drug: CCH-aaes
• 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.
  Intervention: Drug: CCH-aaes
• 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.
  Intervention: Drug: CCH-aaes
• 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.
  Intervention: Drug: CCH-aaes
• 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.
  Interventions:

  • Drug: CCH-aaes
  • Drug: Antifibrinolytic Agent

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 18, 2023): 91
• Original Estimated Enrollment (submitted: June 10, 2022): 180
• Estimated Study Completion Date: May 2023
• Actual Primary Completion Date: January 3, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05419505
• Other Study ID Numbers: EN3835-226
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)

• Current Responsible Party: Endo Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Endo Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: David Hernandez; Endo Pharmaceuticals

• PRS Account: Endo Pharmaceuticals
• Verification Date: January 2023