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

Phase 2

Completed

• Conditions: Edematous Fibrosclerotic Panniculopathy (EFP)
• Interventions: Biological: Collagenase Clostridium Histolyticum; Biological: Placebo

• Registration Number: NCT01987986
• Lead Sponsor: Endo Pharmaceuticals

Brief 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.

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 Timeline

• Study Start: 2013-10
• Study First Submitted: 2013-10-30
• Study First Submitted QC: 2013-11-13
• Study First Posted: 2013-11-20
• Primary Completion: 2014-08
• Study Completion: 2014-08
• Disposition First Submitted: 2015-03-17
• Disposition First Submitted QC: 2015-03-17
• Disposition First Posted: 2015-04-03
• Results First Submitted: 2017-04-18
• Results First Submitted QC: 2017-05-31
• Results First Posted: 2017-07-02
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-07
• Last Update Posted: 2017-10-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 150

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AA4500 0.06 mg (low dose)	Collagenase Clostridium Histolyticum	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days.
AA4500 0.84 mg (high dose)	Collagenase Clostridium Histolyticum	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days.
Placebo	Placebo	Placebo Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days.
AA4500 0.48 mg (mid-dose)	Collagenase Clostridium Histolyticum	AA4500 (Collagenase Clostridium Histolyticum) Each subject could receive up to three treatment sessions. Each treatment session was separated by approximately 21 days.

Primary Outcome Measures

Name	Time	Method
Investigator Global Assessment of Aesthetic Improvement	Baseline, Day 73	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).

Trial Locations

Locations (10)

Stony Brook University Medical Center; 🇺🇸 Stony Brook, New York, United States

Dermatology Cosmetic Laser Medical Associates of La Jolla; 🇺🇸 San Diego, California, United States

ATS Clinical Research; 🇺🇸 Santa Monica, California, United States

Mercy Health Research; 🇺🇸 Washington, Missouri, United States

Sadick Research Group; 🇺🇸 New York, New York, United States

Dermatology Research Institute; 🇺🇸 Coral Gables, Florida, United States

Kenneth Beer, MD PA; 🇺🇸 West Palm Beach, Florida, United States

Premier Clinical Research; 🇺🇸 Spokane, Washington, United States

Charlottesville Dermatology; 🇺🇸 Charlottesville, Virginia, United States

Tennessee Clinical Research Center; 🇺🇸 Nashville, Tennessee, United States