A Phase 2, Randomized, Double-blind, Placebo Controlled Dose Ranging Study of Repeat Doses of AA4500 for the Treatment of Edematous Fibrosclerotic Panniculopathy

A Phase 2, Double-blind and Placebo Dose Ranging Study of Repeat Doses of AA4500 for the Treatment of Edematous Fibrosclerotic Panniculopathy

To assess the safety and effectiveness of repeat doses of AA4500 in the treatment of edematous fibrosclerotic panniculopathy (EFP) commonly known as cellulite in adult women.

Study Overview

• Status: Completed
• Conditions: Edematous Fibrosclerotic Panniculopathy (EFP)
• Intervention / Treatment: Biological: Placebo; Biological: Collagenase Clostridium Histolyticum

Detailed Description

The Phase 2a study is a randomized, double-blind multiple-dose study that is expected to enroll approximately 144 women between the ages of 18 and 45 in the United States. Treatment effectiveness will be evaluated by investigator and patient assessments, as well as 3-D photographic imaging techniques. Once the safety and local tolerability profile from the first stage has been found to be acceptable subjects will be enrolled in stage 2. After an interim safety and local tolerability review was completed of all subjects in stage 1, it was determined that enrollment in stage 2 is acceptable and has been initiated.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92121
      • Dermatology Cosmetic Laser Medical Associates of La Jolla
    • Santa Monica, California, United States, 90404
      • ATS Clinical Research
  • Florida
    • Coral Gables, Florida, United States, 33146
      • Dermatology Research Institute
    • West Palm Beach, Florida, United States, 33401
      • Kenneth Beer, MD PA
  • Missouri
    • Washington, Missouri, United States, 63090
      • Mercy Health Research
  • New York
    • New York, New York, United States, 10075
      • Sadick Research Group
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37215
      • Tennessee Clinical Research Center
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Dermatology
  • Washington
    • Spokane, Washington, United States, 99204
      • Premier Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Be a female between 18 to 45 years of age.
2. Have at least one well defined dimple that is at least 1 cm but not more than 2 cm along the long axis and that is evident when the subject is standing
3. Have a photonumeric cellulite severity scale (CSS) score between 6 and 12
4. Have a Body Mass Index (BMI) >19 and <30 kg/m2, and intends to maintain stable body weight throughout the duration of the study
5. Be willing to apply appropriate sunscreen to the selected quadrant before each exposure to the sun while participating in the study
6. Be judged to be in good health, based upon the results of a medical history, physical examination, and laboratory profile at screening.
7. Have a negative urine pregnancy test at screening and before injection of AA4500 and be using an effective contraception method (ie, abstinence, intrauterine device [IUD], hormonal [estrogen/progestin] contraceptives, or barrier control) for at least one menstrual cycle prior to study enrollment and for the duration of the study.
8. Be willing and able to cooperate with the requirements of the study.
9. Voluntarily sign and date an informed consent agreement approved by the Institutional Review Board/Independent Ethics Committee/Human Research Ethics Committee (IRB/IEC/HREC).
10. Be able to read, complete and understand the Patient Reported Outcomes rating instruments in English.

Exclusion Criteria:

1. Thyroid disease, unless controlled with medication for ≥ 6 months
2. Uncontrolled diabetes mellitus, as determined by the investigator
3. Uncontrolled hypertension, as determined by the investigator
4. Vascular disorder (eg, phlebitis or varicose veins) in area to be treated
5. Lipedema or a lymphatic disorder
6. Cushing's disease and/or use of systemic corticosteroids
7. History of lower extremity thrombosis or post-thrombosis syndrome
8. Documented autoimmune disorder such as lupus erythematosus, rheumatoid arthritis
9. Inflammation or active infection in area to be treated
10. Cutaneous alteration in area to be treated
11. Rash, eczema, psoriasis, or skin cancer in the area to be treated
12. History of keloidal scarring or abnormal wound healing
13. Coagulation disorder
14. Taking a medication for chronic anticoagulation (except for ≤ 150 mg aspirin daily)
15. Known active hepatitis A, B or C
16. Known immune deficiency disease or a positive test for human immunodeficiency virus (HIV)
17. Other significant conditions including body dysmorphic disorder, which in the investigator's opinion would make the subject unsuitable for enrollment in the study
18. Is menopausal defined as 12 months of amenorrhea in the absence of other biological or physiological causes, as determined by the investigator

19. Has used any of the following for the treatment of EFP on the legs or buttock within the timelines identified below or intends to use any of the following at any time during the course of the study:

    • Liposuction on the side of the body selected for treatment during the 12-month period before injection of AA4500
    • Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; or surgery (including subcision) within the selected treatment quadrant during the 12-month period before injection of AA4500
    • Endermologie or similar treatments within the selected treatment quadrant during the 6-months period before injection of AA4500
    • Massage therapy within the selected treatment quadrant during the 3-month period before injection of AA4500
    • Creams (eg, Celluvera™, TriLastin®) to prevent or mitigate EFP within the selected treatment quadrant during the 2-week period before injection of AA4500
20. Has a tattoo located within 2 cm of the site of injection
21. Is presently nursing a baby or providing breast milk for a baby.
22. Intends to become pregnant during the study.
23. Intends to initiate an intensive sport or exercise program during the study.
24. Has received an investigational drug or treatment within 30 days before injection of AA4500.
25. Has a known systemic allergy to collagenase or any other excipient of AA4500.

26. Has received any collagenase treatments within 30 days before treatment.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: AA4500 0.06 mg (low dose); AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days.	Biological: Collagenase Clostridium Histolyticum; injectible intervention; Other Names: AA4500; Xiaflex; Xiapex
EXPERIMENTAL: AA4500 0.48 mg (mid-dose); AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days.	Biological: Collagenase Clostridium Histolyticum; injectible intervention; Other Names: AA4500; Xiaflex; Xiapex
EXPERIMENTAL: AA4500 0.84 mg (high dose); AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days.	Biological: Collagenase Clostridium Histolyticum; injectible intervention; Other Names: AA4500; Xiaflex; Xiapex
PLACEBO_COMPARATOR: Placebo; Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days.	Biological: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator Global Assessment of Aesthetic Improvement	Investigators assessment of aesthetic improvement (I-GAIS) scores ranged from 3 to -1 as follows: 3 (very much improved), 2 (much improved), 1 (improved), 0 (no change), -1 (worse).	Baseline, Day 73

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator Cellulite Severity Score (CSS) Total Score- Change From Baseline	The CSS is a photonumeric scale that was used to evaluate 5 morphologic features of cellulite; (A) number of evident depressions, (B) depth of depressions, (C) morphological appearance of skin surface alterations, (D) laxity, flaccidity or sagging of skin, and (E) current classification scale based on medical literature including Nuernberger and Mueller. The severity of each feature is rated on a scale from 0 (none) to 3 (most severe). The CSS total score is the sum of the 5 cellulite features (range: 0 to 15, with higher scores corresponding to more severe cellulite). Change is Day 73 study visit rating minus baseline rating; negative values indicate improvement in cellulite.	Baseline, Day 73
Subject Cellulite Severity Item (CSI)-Change From Baseline	CSI scores ranged from 0 (no cellulite present), 1 (very mild), 2 (mild), 3 (moderate), 4 (severe) to 5 (very severe). Change is Day 73 study visit rating minus baseline rating; negative values indicate a lessening in cellulite severity.	Baseline, Day 73
Subject Global Bother Assessment (SGBA)- Change From Baseline	Subjects rated their cellulite on a scale from 0 (not at all bothered) to 4 (extremely bothered). Change from baseline is Day 73 study visit value minus baseline value; negative change reflects an improvement in the amount the subject was bothered by cellulite; positive change reflects a worsening in the amount the subject is bothered by cellulite.	Baseline, Day 73
Subject-reported Cellulite Impact Scale (SR-CIS)-Change From Baseline	Subjects were asked to answer 6 exploratory questions regarding the appearance of their cellulite on a scale of 0 to 10 with 0 representing "not at all" and 10 representing "extremely." A SR-CIS total score was derived from these 6 questions with values varying from 0 (No negative impact) to 60 (Extreme negative impact). Change from baseline is Day 73 value minus baseline value; negative change reflects an improvement.	Baseline, Day 73
Subject Satisfaction With Treatment Assessment (SCTA)	Subjects rated their treatment satisfaction at the Day 73 visit on a 5-point scale ranging from -2 (very dissatisfied) to +2 (very satisfied)	Day 73
Subject Global Assessment Cellulite (SGA-C)	Subjects assessed their cellulite based on a 5-point scale from -1 (slightly worse), 0 (same), 1 (slightly improved), 2 (moderately improved), to 3 (much improved) on Day 73	Day 73
Subject Global Assessment of Aesthetic Improvement (C-GAIS)	Subjects's assessment of aesthetic improvement (C-GAIS) scores ranged from 3 to -1 as follows: 3 (very much improved), 2 (much improved), 1 (improved), 0 (no change), -1 (worse).	Day 73

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals
• Investigators: Study Director: Veronica Urdaneta, MD MPH, Endo Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (ACTUAL): August 1, 2014
• Study Completion (ACTUAL): August 1, 2014

Study Registration Dates

• First Submitted: October 30, 2013
• First Submitted That Met QC Criteria: November 13, 2013
• First Posted (ESTIMATE): November 20, 2013

Study Record Updates

• Last Update Posted (ACTUAL): October 5, 2017
• Last Update Submitted That Met QC Criteria: September 7, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: cellulite; dimple; orange peel; cottage cheese; mattress texture
• Additional Relevant MeSH Terms: Edema
• Other Study ID Numbers: AUX-CC-831