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

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ClinicalTrials.gov Identifier: NCT03446781
Recruitment Status : Completed
First Posted : February 27, 2018
Results First Posted : October 8, 2020
Last Update Posted : October 8, 2020
Sponsor:
Information provided by (Responsible Party):
Endo Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE February 4, 2018
First Posted Date  ICMJE February 27, 2018
Results First Submitted Date  ICMJE August 5, 2020
Results First Posted Date  ICMJE October 8, 2020
Last Update Posted Date October 8, 2020
Actual Study Start Date  ICMJE February 8, 2018
Actual Primary Completion Date September 26, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 15, 2020)
2-level Composite Responders for the Target Buttock [ Time Frame: Day 71 ]
Proportion of 2-level Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) / Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) composite responders in the target buttock at Day 71. CR-PCSS and PR-PCSS is a 5-level scale ranging from "0" (None) to "4" (Severe). A 2-level composite responder is defined as a participant with improvement from baseline of at least 2-levels of severity in the CR-PCSS and an improvement from baseline of at least 2-levels of severity in the PR-PCSS of the target buttock. A participant who missed one or two assessments of CR-PCSS and PR-PCSS at Day 71 was defined as a non-responder.
Original Primary Outcome Measures  ICMJE
 (submitted: February 23, 2018)
  • Improvement in severity of target buttock from baseline of at least 2 levels of severity in Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) [ Time Frame: 71 days ]
    Scale is 5-levels, 0=None to 4=Severe
  • Improvement in severity of target buttock from baseline of at least 2 levels of severity in Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) [ Time Frame: 71 days ]
    Scale is 5-levels, 0=None to 4=Severe
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 15, 2020)
  • 1-level PR-PCSS Responders of the Target Buttock [ Time Frame: Day 71 ]
    Improvement in cellulite severity of the Target Buttock from baseline of at least 1-level of severity in Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS). PR-PCSS is a 5-level scale ranging from "0" (None) to "4" (Severe).
  • 2-level PR-PCSS Responders of the Target Buttock [ Time Frame: Day 71 ]
    Improvement in cellulite severity of the Target Buttock from baseline of at least 2-levels of severity in Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS). PR-PCSS is a 5-level scale ranging from "0" (None) to "4" (Severe).
  • 1-level Composite Responders of the Target Buttock [ Time Frame: Day 71 ]
    Improvement in cellulite severity of the Target Buttock from baseline of at least 1-level of severity in Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) / Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS). PR-PCSS and CR-PCSS is a 5-level scale ranging from "0" (None) to "4" (Severe).
  • 2-level Composite Responders of the Non-target Buttock [ Time Frame: Day 71 ]
    Improvement in cellulite severity of the Non-target Buttock from baseline of at least 2-levels of severity in Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) / Clinician -Reported Photonumeric Cellulite Severity Scale (CR-PCSS). PR-PCSS and CR-PCSS is a 5-level scale ranging from "0" (None) to "4" (Severe).
  • 1-level SSRS Responders [ Time Frame: Day 71 ]
    Subject Self-Rating Scale (SSRS) is a measure that assesses participant satisfaction with appearance in association with cellulite on the buttocks using whole numbers on a 7-level scale that ranges from "0" (Extremely Dissatisfied) to "6" (Extremely Satisfied). A 1-level SSRS responder is defined as a participant who is at least slightly satisfied (Slightly Satisfied [4], Very Satisfied [5], or Extremely Satisfied [6]) with the appearance of the cellulite on her buttocks at Day 71.
  • Change From Baseline in PR-CIS Total Score [ Time Frame: Day 71 ]
    Patient-Reported Cellulite Impact Scale (PR-CIS) is a 6-item static questionnaire, each item is answered by a participant on a 11-level numerical rating scale that ranges from "0" (Not at all) to "10" (Extremely). The PR-CIS total score is the sum of individual item scores and can range from "0" to "60" with higher numbers reflecting a more negative impact from the cellulite. A responder is defined as a participant with a reduction in the PR-CIS total score of at least 12 from baseline at evaluation time point. A negative change from baseline indicates an improvement in cellulite severity.
  • 1-level S-GAIS Responders of Target Buttock [ Time Frame: Day 71 ]
    Subject Global Aesthetic Improvement Scale (S-GAIS) is a measure that assesses participant rating of cellulite appearance after treatment. This scale has 7-levels ranging from "+3" (Very Much Improved) to "-3" (Very Much Worse). Responders are defined as participants with ≥1-level improvement (Improved, Much Improved or Very Improved) in S-GAIS assessment of the Target Buttock.
  • 2-level S-GAIS Responders of Target Buttock [ Time Frame: Day 71 ]
    Subject Global Aesthetic Improvement Scale (S-GAIS) is a measure that assesses participant rating of cellulite appearance after treatment. This scale has 7-levels ranging from "+3" (Very Much Improved) to "-3" (Very Much Worse). Responders are defined as participants with ≥ 2-level improvement (Much Improved or Very Much Improved) in S-GAIS assessment of the Target Buttock.
  • PR-PCSS Rating for the Target and Non-target Buttock by Visit [ Time Frame: Day 71 ]
    The Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) is a 5-level photonumeric scale used by the patient (participant) to assess the severity of the participant's cellulite. The ratings range from "0" (None) to "4" (Severe).
  • Subjects Satisfaction With Cellulite Treatment [ Time Frame: Day 71 ]
    A 1-level Subject Satisfaction Responder is defined as a participant who is at least satisfied (Satisfied [+1], or Very Satisfied [+2]) with the appearance of the cellulite on her buttocks at the Day 71 visit. A positive change indicates an improvement in cellulite.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 23, 2018)
  • Proportion of 1-level PR-PCSS responders defined as subjects with ≥1-level improvement in PR-PCSS severity rating of the target buttock [ Time Frame: 71 Days ]
    Scale is 5-levels, 0=None to 4=Severe
  • Proportion of 2-level PR-PCSS responders defined as subjects with ≥2-level improvement in PR-PCSS severity rating of target buttock [ Time Frame: 71 Days ]
    Scale is 5-levels, 0=None to 4=Severe
  • Proportion of 1-level composite responders of target buttock (subjects with improvement in severity from baseline of at least 1 level of severity in CR-PCSS and improvement of severity from baseline of at least 1 level of severity in the PR-PCSS) [ Time Frame: 71 Days ]
    Scales are 5-levels, 0=None to 4=Severe
  • Proportion of 2-level composite responders of the non-target buttock [ Time Frame: 71 Days ]
    Scales are 5-levels, 0=None to 4=Severe
  • Proportion of 1-level Subject Self Rating Scale responders defined as subjects who were at least slightly satisfied (Scale is 7 levels, 0=Extremely Dissatisfied to 6=Extremely Satisfied) [ Time Frame: 71 Days ]
  • Change from baseline (Day 1) of the Patient Reported Cellulite Impact Scale total score (Scale 11 levels; 0=Not at All to 10=Extremely) [ Time Frame: 71 Days ]
  • Proportion of 1-level Subject Global Aesthetic Improvement Scale (S-GAIS) responders defined as subjects with ≥1-level improvement (improved, much improved or very much improved) in S-GAIS assessment of the target buttock [ Time Frame: 71 Days ]
  • Proportion of 2-level S-GAIS responders defined as subjects with ≥2-level improvement (much improved or very much improved) in the assessment of the target buttock [ Time Frame: 71 Days ]
Current Other Pre-specified Outcome Measures
 (submitted: September 15, 2020)
  • Serum Antibody Positivity by Visit [ Time Frame: Day 1 - Day 71 ]
    Percent of participants that are seropositive. Percentages were based on the number of subjects who had immunogenicity lab samples analyzed at the visit.
  • Overall Antibody Titer Levels by Visit [ Time Frame: Day 1 - Day 71 ]
    Descriptive statistics were based on log10 transformation of titer levels. Titer levels were imputed as 10 before the transformation if the reported level is "<10". Only seropositive participants are summarized.
  • Presence of Neutralizing Antibody (Seropositivity) at Day 71 (LOCF) by Antidrug Antibody Log Titer Quartiles [ Time Frame: Day 71 ]
    Q1 and Q4 are based on the ADA titer levels.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effectiveness and Safety of EN3835 in the Treatment of Cellulite in Women
Official Title  ICMJE A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Of EN3835 In The Treatment Of Edematous Fibrosclerotic Panniculopathy (Cellulite)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Edematous Fibrosclerotic Panniculopathy (Cellulite)
Intervention  ICMJE
  • Biological: EN3835
    Collagenase clostridium histolyticum
  • Biological: Placebo
    Placebo
Study Arms  ICMJE
  • Active Comparator: EN3835 Active
    EN3835 0.84mg (Collagenase Clostridium Histolyticum)
    Intervention: Biological: EN3835
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Biological: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 2, 2018)
422
Original Estimated Enrollment  ICMJE
 (submitted: February 23, 2018)
420
Actual Study Completion Date  ICMJE September 26, 2018
Actual Primary Completion Date September 26, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03446781
Other Study ID Numbers  ICMJE EN3835-303
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Endo Pharmaceuticals
Study Sponsor  ICMJE Endo Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Michael McLane Endo Pharmaceuticals
PRS Account Endo Pharmaceuticals
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP