Clinical trial NCT03428750: Effectiveness and Safety of EN3835 in the Treatment of EFP (Cellulite) in Women
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of EN3835 In The Treatment Of Edematous Fibrosclerotic Panniculopathy (Cellulite)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Edematous Fibrosclerotic Panniculopathy (Cellulite)
Lead sponsor: Endo Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-02-12
Enrollment: 423
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 2-level Composite Responders for the Target Buttock
timeFrame: Day 71
Secondary outcomes:
measure: 1-level PR-PCSS Responders of the Target Buttock
timeFrame: Day 71
measure: 2-level PR-PCSS Responders of the Target Buttock
timeFrame: Day 71
measure: 1-level Composite Responders of the Target Buttock
timeFrame: Day 71
measure: 2-level Composite Responder of the Non-target Buttock
timeFrame: Day 71
measure: 1-level SSRS Responders
timeFrame: Day 71
measure: Change From Baseline in PR-CIS Total Score
timeFrame: 71 Days
measure: 1-level S-GAIS Responders of Target Buttock
timeFrame: Day 71
measure: 2-level S-GAIS Responders of Target Buttock
timeFrame: Day 71
measure: PR-PCSS Rating for the Target and Non-target Buttock by Visit
timeFrame: Day 1 to Day 71
measure: Subjects Satisfaction With Cellulite Treatment at Day 71
timeFrame: Day 71
Other outcomes:
measure: Serum Antibody Positivity by Visit
timeFrame: Day 1 - Day 71
measure: Overall Antibody Titer Levels by Visit
timeFrame: Day 1 - Day 71
measure: Presence of Neutralizing Antibody (Seropositivity) at Day 71 (LOCF) by Antidrug Antibody Log Titer Quartiles
timeFrame: Day 71
Locations:
city: Scottsdale
country: United States
facility: Endo Clinical Trial Site #1
state: Arizona
city: Encinitas
country: United States
facility: Endo Clinical Trial Site #2
state: California
city: Long Beach
country: United States
facility: Endo Clinical Trial Site #3
state: California
city: Los Angeles
country: United States
facility: Endo Clinical Trial Site #4
state: California
city: Oceanside
country: United States
facility: Endo Clinical Trial Site #5
state: California
city: San Diego
country: United States
facility: Endo Clinical Trial Site #6
state: California
city: Boca Raton
country: United States
facility: Endo Clinical Trial Site #7
state: Florida
city: Largo
country: United States
facility: Endo Clinical Trial Site #8
state: Florida
city: Miami
country: United States
facility: Endo Clinical Trial Site #9
state: Florida
city: Snellville
country: United States
facility: Endo Clinical Trial Site #10
state: Georgia
city: Chicago
country: United States
facility: Endo Clinical Trial Site #11
state: Illinois
city: New Orleans
country: United States
facility: Endo Clinical Trial Site #12
state: Louisiana
city: Chestnut Hill
country: United States
facility: Endo Clinical Trial Site #13
state: Massachusetts
city: Quincy
country: United States
facility: Endo Clinical Trial Site #14
state: Massachusetts
city: Fridley
country: United States
facility: Endo Clinical Trial Site #15
state: Minnesota
city: Washington
country: United States
facility: Endo Clinical Trial Site #16
state: Missouri
city: Omaha
country: United States
facility: Endo Clinical Trial Site #17
state: Nebraska
city: Mount Kisco
country: United States
facility: Endo Clinical Trial Site #18
state: New York
city: New York
country: United States
facility: Endo Clinical Trial Site #21
state: New York
city: New York
country: United States
facility: Endo Clinical Trial Site #19
state: New York
city: New York
country: United States
facility: Endo Clinical Trial Site #20
state: New York
city: Cincinnati
country: United States
facility: Endo Clinical Trial Site #22
state: Ohio
city: Houston
country: United States
facility: Endo Clinical Trial Site #23
state: Texas
city: Pflugerville
country: United States
facility: Endo Clinical Trial Site #24
state: Texas
city: Sugar Land
country: United States
facility: Endo Clinical Trial Site #25
state: Texas
city: Charlottesville
country: United States
facility: Endo Clinical Trial Site #26
state: Virginia
Study officials:
affiliation: Endo Pharmaceuticals
name: Michael McLane
role: STUDY_DIRECTOR
References:
citation: Kaufman-Janette J, Joseph JH, Kaminer MS, Clark J, Fabi SG, Gold MH, Goldman MP, Katz BE, Peddy K, Schlessinger J, Young VL, Davis M, Hurley D, Liu G, McLane MP, Vijayan S, Bass LS. Collagenase Clostridium Histolyticum-aaes for the Treatment of Cellulite in Women: Results From Two Phase 3 Randomized, Placebo-Controlled Trials. Dermatol Surg. 2021 May 1;47(5):649-656. doi: 10.1097/DSS.0000000000002952.