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CompletedNCT03329989Updated Dec 29, 2020Results posted

Safety and Effectiveness of EN3835 in the Treatment of EFP in Women

A Phase 2 interventional study of Collagenase Clostridium Histolyticum in Edematous Fibrosclerotic Panniculopathy and Cellulite, sponsored by Endo Pharmaceuticals. Completed at 11 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-12-29.

Sponsored by Endo Pharmaceuticals · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
158
Allocation
Not applicable
Ages
18 Years and older
Sex
Female
01

Study summary

An open-label study of safety and effectiveness of EN3835 in the treatment of cellulite in adult women.

02

Conditions studied

  • Edematous Fibrosclerotic Panniculopathy
  • Cellulite

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03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  1. Voluntarily sign and date an informed consent agreement
  2. Be a female ≥18 years of age

  3. At Screening visit, have at least 2 bilateral quadrants with each quadrant having:

    1. a score of 2 (mild) or greater as reported by the Investigator (CR-PCSS), and
    2. a Hexsel CSS score no greater than 13

  4. At Day 1 visit, have assigned bilateral quadrants with each quadrant having:

    1. a score of 2 (mild) or greater as reported by the Investigator (CR-PCSS), and
    2. a Hexsel CSS score no greater than 13
  5. Be willing to apply sunscreen to the assigned treatment quadrants before each exposure to the sun while participating in the study (i.e., 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 (e.g., 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

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 area to be treated:

    1. History of lower extremity thrombosis or post-thrombosis syndrome
    2. Vascular disorder (e.g., varicose veins, telangiectasia) in area to be treated
    3. Inflammation or active infection
    4. Active cutaneous alteration including rash, eczema, psoriasis, or skin cancer
    5. 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 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:

    1. Liposuction in the areas of the body selected for treatment during the 12-month period before injection of study drug
    2. Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; buttock and/or thigh implant treatment, or surgery (including subcision and/or powered subcision) within the assigned treatment quadrants during the 12-month period before injection of study drug
    3. Endermologie or similar treatments within the assigned treatment quadrants during the 6 month period before injection of study drug
    4. Massage therapy within the assigned treatment quadrants during the 3-month period before injection of study drug
    5. Creams (eg, Celluvera™, TriLastin®) to prevent or mitigate EFP within the assigned treatment quadrants 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 collagenase clostridium histolyticum (CCH) : AUX-CC-830, AUX-CC-831, EN3835-102, EN3835-104, EN3835-201, and/or EN3835-202
  14. Any other condition(s) that, in the Investigator's opinion, might indicate the subject to be unsuitable for the study.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
158 participants (actual)

Study arms

  • Experimental
    EN3835 Active

    EN3835 0.84mg (Collagenase Clostridium Histolyticum)

    Biological: Collagenase Clostridium Histolyticum

Interventions

  • BiologicalCollagenase Clostridium Histolyticum

    During 3 treatment visits 12 injections will be given per treatment area

    Also known as: Xiaflex

05

What researchers measure

Primary outcomes

  1. Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 2-level Responders

    Percentage of responders defined as participants with an improvement in cellulite severity from baseline of at least 2-levels of severity of at least one buttock (left or right) on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) with ratings ranging from "0" (None) to "4" (Severe). A 2-level responder is a participant with a reduction in severity of at least 2-levels from Baseline at that particular visit. Number of participants analyzed is determined by observed participants at each visit.

    Time frame: Day 22, 43, 90, and 180

Secondary outcomes

  1. Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 1-level Responders

    Percentage of responders defined as participants with an improvement in cellulite severity from baseline of at least 1-level of severity of at least one buttock (left or right) on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) with ratings ranging from "0" (None) to "4" (Severe). A 1-level responder is a participant with a reduction in severity of at least 1-level from Baseline at that particular visit. Percentages are based on the observed counts. Number of participants analyzed is determined by observed participants at each visit.

    Time frame: Day 22, 43, 90, and 180

  2. Subject Satisfaction With Cellulite Treatment Assessment at End of Study

    At Day 180, participants rated their satisfaction with cellulite treatment using the 5-point subject satisfaction scale. Ratings range from Very Satisfied with Treatment (2), Satisfied with Treatment (1), Neither Dissatisfied nor Satisfied with Treatment (0), Dissatisfied with Treatment (-1), and Very Dissatisfied with Treatment (-2). Percentages are based on the observed counts.

    Time frame: Day 180

Other outcomes

  1. Overall Anti-AUX-I Serum Antibody by Visit

    Percent of participants that are seropositive. Descriptive statistics were based on log10 transformation of titer levels. Percentages were based on the number of subjects who had immunogenicity lab samples drawn at the visit. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.

    Time frame: Day 1 to Day 180

  2. Overall Anti-AUX-I Antibody Log Titer Levels by Visit

    Descriptive statistics were based on log10 transformation of titer levels. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.

    Time frame: Day 1 to Day 180

  3. Overall Anti-AUX-II Serum Antibody by Visit

    Percent of participants that are seropositive. Descriptive statistics were based on log10 transformation of titer levels. Percentages were based on the number of subjects who had immunogenicity lab samples drawn at the visit. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.

    Time frame: Day 1 to Day 180

  4. Overall Anti-AUX-II Antibody Log Titer Levels by Visit

    Descriptive statistics were based on log10 transformation of titer levels. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.

    Time frame: Day 1 to Day 180

  5. Anti-AUX-I Neutralizing Antibodies by Visit

    A subset of all CCH Treated participants who had positive binding antibody titer levels were tested for the presence or absence of Neutralizing Antibodies. Overall Number of Participants Analyzed is determined by the number of participants in the highest and lowest quartiles at Day 90 (Q1 and Q4) of seropositive participants at each of two visits (Day 90 and Day 180).

    Time frame: Day 1 to Day 180

  6. Anti-AUX-II Neutralizing Antibodies by Visit

    A subset of all CCH Treated participants who had positive binding antibody titer levels were tested for the presence or absence of Neutralizing Antibodies. Overall Number of Participants Analyzed is determined by the number of participants in the study. Number of Participants Analyzed is determined by observed participants that had a seropositive sample at each visit and the antibody level at Day 71 in Q1 and Q4.

    Time frame: Day 1 to Day 180

06

Results

Posted Nov 23, 2020

Participant flow

Participant flow — Overall Study
MilestoneCollagenase Clostridium Histolyticum (CCH)
Started158
Completed135
Not completed23
Withdrew: Withdrawal by subject9
Withdrew: Lost to follow-up8
Withdrew: Adverse event5
Withdrew: Protocol violation1

Outcome measures

PrimaryInvestigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 2-level Responders

Percentage of responders defined as participants with an improvement in cellulite severity from baseline of at least 2-levels of severity of at least one buttock (left or right) on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) with ratings ranging from "0" (None) to "4" (Severe). A 2-level responder is a participant with a reduction in severity of at least 2-levels from Baseline at that particular visit. Number of participants analyzed is determined by observed participants at each visit.

Time frame:
Day 22, 43, 90, and 180
Reported as:
Count of participants · Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 2-level Responders
ParticipantsCollagenase Clostridium Histolyticum (CCH)
At Least One of two areas (Left & Right): Day 22 — Yes6
At Least One of two areas (Left & Right): Day 22 — No131
At Least One of two areas (Left & Right): Day 43 — Yes8
At Least One of two areas (Left & Right): Day 43 — No125
At Least One of two areas (Left & Right): Day 90 — Yes17
At Least One of two areas (Left & Right): Day 90 — No110
At Least One of two areas (Left & Right): Day 180 — Yes20
At Least One of two areas (Left & Right): Day 180 — No111
SecondaryInvestigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 1-level Responders

Percentage of responders defined as participants with an improvement in cellulite severity from baseline of at least 1-level of severity of at least one buttock (left or right) on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) with ratings ranging from "0" (None) to "4" (Severe). A 1-level responder is a participant with a reduction in severity of at least 1-level from Baseline at that particular visit. Percentages are based on the observed counts. Number of participants analyzed is determined by observed participants at each visit.

Time frame:
Day 22, 43, 90, and 180
Reported as:
Count of participants · Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 1-level Responders
ParticipantsCollagenase Clostridium Histolyticum (CCH)
At Least One of Two Areas (Left & Right): Day 22 — Yes55
At Least One of Two Areas (Left & Right): Day 22 — No82
At Least One of Two Areas (Left & Right): Day 43 — Yes87
At Least One of Two Areas (Left & Right): Day 43 — No46
At Least One of Two Areas (Left & Right): Day 90 — Yes96
At Least One of Two Areas (Left & Right): Day 90 — No31
At Least One of Two Areas (Left & Right): Day 180 — Yes90
At Least One of Two Areas (Left & Right): Day 180 — No41
SecondarySubject Satisfaction With Cellulite Treatment Assessment at End of Study

At Day 180, participants rated their satisfaction with cellulite treatment using the 5-point subject satisfaction scale. Ratings range from Very Satisfied with Treatment (2), Satisfied with Treatment (1), Neither Dissatisfied nor Satisfied with Treatment (0), Dissatisfied with Treatment (-1), and Very Dissatisfied with Treatment (-2). Percentages are based on the observed counts.

Time frame:
Day 180
Reported as:
Count of participants · Participants
Subject Satisfaction With Cellulite Treatment Assessment at End of Study
ParticipantsCollagenase Clostridium Histolyticum (CCH)
Very Satisfied with Treatment (2)25
Satisfied with Treatment (1)48
Neither Dissatisfied nor Satisfied with Treatment32
Dissatisfied with Treatment (-1)12
Very Dissatisfied with Treatment (-2)13
Other pre-specifiedOverall Anti-AUX-I Serum Antibody by Visit

Percent of participants that are seropositive. Descriptive statistics were based on log10 transformation of titer levels. Percentages were based on the number of subjects who had immunogenicity lab samples drawn at the visit. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.

Time frame:
Day 1 to Day 180
Reported as:
Count of participants · Participants
Overall Anti-AUX-I Serum Antibody by Visit
ParticipantsCollagenase Clostridium Histolyticum (CCH)
Anti-AUX-I: Day 1 — Seropositive4
Anti-AUX-I: Day 1 — Seronegative152
Anti-AUX-I: Day 22 — Seropositive104
Anti-AUX-I: Day 22 — Seronegative43
Anti-AUX-I: Day 43 — Seropositive141
Anti-AUX-I: Day 43 — Seronegative2
Anti-AUX-I: Day 90 — Seropositive134
Anti-AUX-I: Day 90 — Seronegative0
Anti-AUX-I: Day 180 — Seropositive134
Anti-AUX-I: Day 180 — Seronegative1
Other pre-specifiedOverall Anti-AUX-I Antibody Log Titer Levels by Visit

Descriptive statistics were based on log10 transformation of titer levels. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.

Time frame:
Day 1 to Day 180
Reported as:
Mean · log 10 titer
Overall Anti-AUX-I Antibody Log Titer Levels by Visit
log 10 titerCollagenase Clostridium Histolyticum (CCH)
Anti-AUX-I: Day 1 positive2.046 ± 1.012
Anti-AUX-I: Day 22 positive2.268 ± 1.076
Anti-AUX-I: Day 43 positive4.681 ± 0.924
Anti-AUX-I: Day 90 positive5.937 ± 0.686
Anti-AUX-I: Day 180 positive5.556 ± 0.981
Other pre-specifiedOverall Anti-AUX-II Serum Antibody by Visit

Percent of participants that are seropositive. Descriptive statistics were based on log10 transformation of titer levels. Percentages were based on the number of subjects who had immunogenicity lab samples drawn at the visit. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.

Time frame:
Day 1 to Day 180
Reported as:
Count of participants · Participants
Overall Anti-AUX-II Serum Antibody by Visit
ParticipantsCollagenase Clostridium Histolyticum (CCH)
Anti-AUX-I: Day 1 — Seropositive6
Anti-AUX-I: Day 1 — Seronegative150
Anti-AUX-I: Day 22 — Seropositive50
Anti-AUX-I: Day 22 — Seronegative98
Anti-AUX-I: Day 43 — Seropositive138
Anti-AUX-I: Day 43 — Seronegative5
Anti-AUX-I: Day 90 — Seropositive131
Anti-AUX-I: Day 90 — Seronegative0
Anti-AUX-I: Day 180 — Seropositive130
Anti-AUX-I: Day 180 — Seronegative5
Other pre-specifiedOverall Anti-AUX-II Antibody Log Titer Levels by Visit

Descriptive statistics were based on log10 transformation of titer levels. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.

Time frame:
Day 1 to Day 180
Reported as:
Mean · log 10 titer
Overall Anti-AUX-II Antibody Log Titer Levels by Visit
log 10 titerCollagenase Clostridium Histolyticum (CCH)
Anti-AUX-II: Day 1 positive1.607 ± 0.947
Anti-AUX-II: Day 22 positive1.942 ± 1.068
Anti-AUX-II: Day 43 positive3.641 ± 1.068
Anti-AUX-II: Day 90 positive5.255 ± 0.809
Anti-AUX-II: Day 180 positive5.141 ± 0.913
Other pre-specifiedAnti-AUX-I Neutralizing Antibodies by Visit

A subset of all CCH Treated participants who had positive binding antibody titer levels were tested for the presence or absence of Neutralizing Antibodies. Overall Number of Participants Analyzed is determined by the number of participants in the highest and lowest quartiles at Day 90 (Q1 and Q4) of seropositive participants at each of two visits (Day 90 and Day 180).

Time frame:
Day 1 to Day 180
Reported as:
Count of participants · Participants
Anti-AUX-I Neutralizing Antibodies by Visit
ParticipantsCollagenase Clostridium Histolyticum (CCH)
anti-AUX-I Neutralizing Antibody: Day 1 — Positive0
anti-AUX-I Neutralizing Antibody: Day 1 — Negative1
anti-AUX-I Neutralizing Antibody: Day 90 — Positive26
anti-AUX-I Neutralizing Antibody: Day 90 — Negative8
anti-AUX-I Neutralizing Antibody: Day 180 — Positive19
anti-AUX-I Neutralizing Antibody: Day 180 — Negative14
Other pre-specifiedAnti-AUX-II Neutralizing Antibodies by Visit

A subset of all CCH Treated participants who had positive binding antibody titer levels were tested for the presence or absence of Neutralizing Antibodies. Overall Number of Participants Analyzed is determined by the number of participants in the study. Number of Participants Analyzed is determined by observed participants that had a seropositive sample at each visit and the antibody level at Day 71 in Q1 and Q4.

Time frame:
Day 1 to Day 180
Reported as:
Count of participants · Participants
Anti-AUX-II Neutralizing Antibodies by Visit
ParticipantsCollagenase Clostridium Histolyticum (CCH)
anti-AUX-II Neutralizing Antibodies: Day 1 — Positive1
anti-AUX-II Neutralizing Antibodies: Day 1 — Negative0
anti-AUX-II Neutralizing Antibodies: Day 90 — Positive24
anti-AUX-II Neutralizing Antibodies: Day 90 — Negative8
anti-AUX-II Neutralizing Antibodies: Day 180 — Positive20
anti-AUX-II Neutralizing Antibodies: Day 180 — Negative11

Adverse events

Collected over All (serious and non-serious) AEs, from Day 1 up to Day 180. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Collagenase Clostridium Histolyticum (CCH)0/158 (0%)1/158 (0.6%)158/158 (100%)
Most frequent serious events
Most frequent serious events
EventCollagenase Clostridium Histolyticum (CCH)
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders1/158
Most frequent other events
Most frequent other events
EventCollagenase Clostridium Histolyticum (CCH)
Injection site bruisingGeneral disorders136/158
Injection site painGeneral disorders76/158
Injection site swellingGeneral disorders35/158
Injection site pruritusGeneral disorders27/158
Injection site discolourationGeneral disorders26/158
Injection site noduleGeneral disorders23/158
Injection site warmthGeneral disorders18/158
Injection site haemorrhageGeneral disorders17/158
Injection site massGeneral disorders10/158
Hemosiderin stainSkin and subcutaneous tissue disorders8/158

Baseline characteristics

Age, Continuous
Age, Continuous(years)Collagenase Clostridium Histolyticum (CCH)
Mean44.8 ± 10.41
Sex: Female, Male
Sex: Female, Male(Participants)Collagenase Clostridium Histolyticum (CCH)
Female158
Male0
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Collagenase Clostridium Histolyticum (CCH)
Hispanic or Latino44
Not Hispanic or Latino114
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Collagenase Clostridium Histolyticum (CCH)
American Indian or Alaska Native0
Asian2
Native Hawaiian or Other Pacific Islander0
Black or African American17
White135
More than one race4
Unknown or Not Reported0
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)Collagenase Clostridium Histolyticum (CCH)
Mean26.74 ± 5.259
Skin Category (Fitzpatrick Scale)
Skin Category (Fitzpatrick Scale)(Participants)Collagenase Clostridium Histolyticum (CCH)
I (Pale White)3
II (Fair)34
III (Darker White)53
IV (Light Brown)48
V (Brown)10
VI (Dark Brown)10
07

Study locations

11 sites
  • Endo Clinical Trial Site #1
    Scottsdale, Arizona 85258, United States
  • Endo Clinical Trial Site #2
    Huntington Beach, California 92647, United States
  • Endo Clinical Trial Site #3
    San Diego, California 92121, United States
  • Endo Clinical Trial Site #4
    Santa Monica, California 90404, United States
  • Endo Clinical Trial Site #5
    Coral Gables, Florida 33146, United States
  • Endo Clinical Trial Site #6
    Tampa, Florida 33626, United States
  • Endo Clinical Trial Site #7
    West Palm Beach, Florida 33401, United States
  • Endo Clinical Trial Site #8
    Alpharetta, Georgia 30022, United States
  • Endo Clinical Trial Site #9
    New York, New York 10003, United States
  • Endo Clinical Trial Site #10
    Franklin, Tennessee 37067, United States
  • Endo Clinical Trial Site #11
    Austin, Texas 78746, United States
08

References and documents

Study documents

  • Study protocol · Aug 31, 2017
  • Statistical analysis plan · Aug 30, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03329989
Lead sponsor
Endo Pharmaceuticals
Responsible party
Sponsor
First posted
Nov 6, 2017
Start date
Nov 17, 2017
Primary completion
Sep 5, 2018
Completion
Sep 5, 2018
Results posted
Nov 23, 2020
Last update
Dec 29, 2020

Study contacts

Mike McLane, PhD
study director · Endo Pharmaceuticals

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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