Effectiveness and Safety of EN3835 in the Treatment of Cellulite in Women (RELEASE-2)

Endo Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Edematous Fibrosclerotic Panniculopathy (Cellulite)

Treatments: Biological: Placebo; Biological: EN3835

Study type: Interventional

Funder types: Industry

Identifiers

NCT03446781

EN3835-303

Details and patient eligibility

About

Subjects will be screened for study eligibility within 14 days prior to enrolling in this study. Subjects with 2 treatment areas (bilateral buttocks) with moderate or severe levels of cellulite as independently assessed by the subject using the Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) and by the Investigator using the Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) will be eligible. The eligibility of the buttocks will be confirmed on Day 1. Once the eligibility of the buttocks is confirmed, subjects will be randomly assigned to a treatment group (EN3835 0.84 mg per buttock or placebo) in a 1:1 ratio within an investigational site. Each subject will receive a treatment course which consists of up to 3 treatment visits (sessions), separated by 21 days (ie, Days 1, 22, and 43). Each treatment visit will consist of 12 injections (0.3 mL per injection of EN3835 0.07 mg/injection or placebo; 0.84 mg in 3.6 mL per buttock) in each of the two buttocks for a total volume of 7.2 mL (1.68 mg). Selection of dimples to be treated in the buttocks will be at the discretion of the Investigator. End of study will occur at study day 71.

Enrollment: 422 patients

Sex: Female

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Voluntarily sign and date an informed consent agreement

2. Be a female ≥18 years of age

3. At Screening visit, have 2 bilateral buttocks with each buttock having:

   1. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and
   2. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS)

4. At Day 1 visit, have 2 bilateral buttocks with each buttock having:

   1. a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and
   2. a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS)

5. Be willing to apply sunscreen to the buttocks before each exposure to the sun while participating in the study (ie, Screening through end of 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 serum pregnancy test at Screening and a negative urine pregnancy test before injection of study drug and be using a stable and effective contraception method (eg, abstinence, intrauterine device [IUD], hormonal [estrogen/progestin] contraceptives, or double barrier method) for at least 1 menstrual cycle prior to study enrollment and for the duration of the study; or be menopausal defined as 12 months of amenorrhea in the absence of other biological or physiological causes, as determined by the Investigator; or post-menopausal for at least 1 year; or be surgically sterile

8. Be willing and able to cooperate with the requirements of the study

9. Be able to read, complete and understand the patient-reported outcomes rating instruments in English

Exclusion criteria

1. Has any of the following systemic conditions:

   1. Coagulation disorder
   2. Evidence or history of malignancy (other than excised basal-cell carcinoma) unless there has been no recurrence in at least 5 years
   3. History of keloidal scarring or abnormal wound healing
   4. Concurrent diseases or conditions that might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the subject's well-being. Any questions about concurrent diseases should be discussed with the Medical Monitor
   5. Evidence of clinically significant abnormalities on physical examination, vital signs, electrocardiogram (ECG), or clinical laboratory values

2. Has any of the following local conditions in the areas to be treated:

   1. History of lower extremity thrombosis or post-thrombosis syndrome
   2. Vascular disorder (eg, varicose veins, telangiectasia) in area to be treated
   3. Inflammation or active infection
   4. Severe skin laxity, flaccidity, and/or sagging
   5. Active cutaneous alteration including rash, eczema, psoriasis, or skin cancer
   6. Has a tattoo and/or a mole located within 2 cm of the site of injection

3. Requires the following concomitant medications before or during participation in the trial:

   a. Anticoagulant or antiplatelet medication or has received anticoagulant or antiplatelet medication (except for ≤150 mg aspirin daily) within 7 days before injection of study drug

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

   1. Liposuction in a buttock during the 12-month period before injection of study drug
   2. Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; buttock implant treatment; cryolipolysis; or surgery (including subcision and/or powered subcision) within a buttock during the 12-month period before injection of study drug
   3. Any investigational treatment for EFP on a buttock during the 12-month period before the injection of study drug
   4. Endermologie or similar treatments within a buttock during the 6-month period before injection of study drug
   5. Massage therapy within a buttock during the 3-month period before injection of study drug
   6. Creams (eg, Celluvera™, TriLastin®) and/or home therapies to prevent or mitigate EFP within a buttock during the 2-week period before injection of study drug

5. Is presently nursing or providing breast milk

6. Intends to become pregnant during the study

7. Intends to initiate an intensive sport or exercise program during the study

8. Intends to initiate a weight reduction program during the study

9. Intends to use tanning spray or tanning booths during the study

10. Has received an investigational drug or treatment within 30 days before injection of study drug

11. Has a known systemic allergy to collagenase or any other excipient of study drug

12. Has received any collagenase treatments at any time prior to treatment

13. Was a subject in a previous cellulite clinical trial of CCH: AUX-CC-830, AUX-CC-831, EN3835-102, EN3835-104, EN3835-201, EN3835-202, and/or EN3835-205

14. Any other condition(s) that, in the Investigator's opinion, might indicate the subject to be unsuitable for the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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422 participants in 2 patient groups, including a placebo group

EN3835 Active

Active Comparator group

Description:

EN3835 0.84mg (Collagenase Clostridium Histolyticum)

Treatment:

Biological: EN3835

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Biological: Placebo