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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Edematous Fibrosclerotic Panniculopathy (EFP)

Intervention / Treatment
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* Biological: Collagenase Clostridium Histolyticum
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be a female between 18 to 45 years of age. 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 Have a photonumeric cellulite severity scale (CSS) score between 6 and 12 Have a Body Mass Index (BMI) >19 and <30 kg/m2, and intends to maintain stable body weight throughout the duration of the study Be willing to apply appropriate sunscreen to the selected quadrant before each exposure to the sun while participating in the study Be judged to be in good health, based upon the results of a medical history, physical examination, and laboratory profile at screening. 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. Be willing and able to cooperate with the requirements of the study. Voluntarily sign and date an informed consent agreement approved by the Institutional Review Board/Independent Ethics Committee/Human Research Ethics Committee (IRB/IEC/HREC). Be able to read, complete and understand the Patient Reported Outcomes rating instruments in English. Exclusion Criteria: Thyroid disease, unless controlled with medication for ≥ 6 months Uncontrolled diabetes mellitus, as determined by the investigator Uncontrolled hypertension, as determined by the investigator Vascular disorder (eg, phlebitis or varicose veins) in area to be treated Lipedema or a lymphatic disorder Cushing's disease and/or use of systemic corticosteroids History of lower extremity thrombosis or post-thrombosis syndrome Documented autoimmune disorder such as lupus erythematosus, rheumatoid arthritis Inflammation or active infection in area to be treated Cutaneous alteration in area to be treated Rash, eczema, psoriasis, or skin cancer in the area to be treated History of keloidal scarring or abnormal wound healing Coagulation disorder Taking a medication for chronic anticoagulation (except for ≤ 150 mg aspirin daily) Known active hepatitis A, B or C Known immune deficiency disease or a positive test for human immunodeficiency virus (HIV) Other significant conditions including body dysmorphic disorder, which in the investigator's opinion would make the subject unsuitable for enrollment in the study Is menopausal defined as 12 months of amenorrhea in the absence of other biological or physiological causes, as determined by the investigator 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 Has a tattoo located within 2 cm of the site of injection Is presently nursing a baby or providing breast milk for a baby. Intends to become pregnant during the study. Intends to initiate an intensive sport or exercise program during the study. Has received an investigational drug or treatment within 30 days before injection of AA4500. Has a known systemic allergy to collagenase or any other excipient of AA4500. Has received any collagenase treatments within 30 days before treatment. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AA4500 0.06 mg (low dose)<br>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<br>* injectible intervention<br>* Other names: Xiapex;|
| Experimental: AA4500 0.48 mg (mid-dose)<br>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<br>* injectible intervention<br>* Other names: Xiapex;|
| Experimental: AA4500 0.84 mg (high dose)<br>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<br>* injectible intervention<br>* Other names: Xiapex;|
| Placebo Comparator: Placebo<br>Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days. | Biological: Placebo<br> <br> |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cellulite, dimple, orange peel, cottage cheese, mattress texture