A Phase 2, Randomized, Double-blind, Placebo Controlled Dose Ranging Study of Repeat Doses of AA4500 for the Treatment of Edematous Fibrosclerotic Panniculopathy
Condition: Edematous Fibrosclerotic Panniculopathy (EFP)
MeSH terms: Edema
Intervention: Collagenase Clostridium Histolyticum; Placebo
Intervention description: injectible intervention
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 150.0
Sex: Female
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: cellulite; dimple; orange peel; cottage cheese; mattress texture

Summary:

      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.
    

Eligibility criteria:

        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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