CompletedNCT03446781RELEASE-2Updated Oct 8, 2020Results posted

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

A Phase 3 interventional study of EN3835 and Placebo in Edematous Fibrosclerotic Panniculopathy (Cellulite), sponsored by Endo Pharmaceuticals. Completed at 25 sites in United States. Open to female participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-10-08.

Sponsored by Endo Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 422
Allocation: Randomized
Ages: 18 Years and older
Sex: Female

Study 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.

Conditions studied

Edematous Fibrosclerotic Panniculopathy (Cellulite)

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Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Female
Accepts healthy volunteers: Yes

Inclusion criteria

Voluntarily sign and date an informed consent agreement
Be a female ≥18 years of age
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)
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)
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)
Be judged to be in good health, based upon the results of a medical history, physical examination, and laboratory profile at Screening
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
Be willing and able to cooperate with the requirements of the study
Be able to read, complete and understand the patient-reported outcomes rating instruments in English

Exclusion criteria

Exclusion Criteria:

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
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
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
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
Is presently nursing or providing breast milk
Intends to become pregnant during the study
Intends to initiate an intensive sport or exercise program during the study
Intends to initiate a weight reduction program during the study
Intends to use tanning spray or tanning booths during the study
Has received an investigational drug or treatment within 30 days before injection of study drug
Has a known systemic allergy to collagenase or any other excipient of study drug
Has received any collagenase treatments at any time prior to treatment
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
Any other condition(s) that, in the Investigator's opinion, might indicate the subject to be unsuitable for the study

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Care provider, Investigator)
Enrollment: 422 participants (actual)

Study arms

Active comparator
EN3835 Active
EN3835 0.84mg (Collagenase Clostridium Histolyticum)
Biological: EN3835
Placebo comparator
Placebo
Placebo
Biological: Placebo

Interventions

BiologicalEN3835
Collagenase clostridium histolyticum
BiologicalPlacebo
Placebo

What researchers measure

Primary outcomes

2-level Composite Responders for the Target Buttock
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.
Time frame: Day 71

Secondary outcomes

1-level PR-PCSS Responders of the Target Buttock
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).
Time frame: Day 71
2-level PR-PCSS Responders of the Target Buttock
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).
Time frame: Day 71
1-level Composite Responders of the Target Buttock
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).
Time frame: Day 71
2-level Composite Responders of the Non-target Buttock
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).
Time frame: Day 71
1-level SSRS Responders
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.
Time frame: Day 71
Change From Baseline in PR-CIS Total Score
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.
Time frame: Day 71
1-level S-GAIS Responders of Target Buttock
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.
Time frame: Day 71
2-level S-GAIS Responders of Target Buttock
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.
Time frame: Day 71
PR-PCSS Rating for the Target and Non-target Buttock by Visit
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).
Time frame: Day 71
Subjects Satisfaction With Cellulite Treatment
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.
Time frame: Day 71

Other outcomes

Serum Antibody Positivity by Visit
Percent of participants that are seropositive. Percentages were based on the number of subjects who had immunogenicity lab samples analyzed at the visit.
Time frame: Day 1 - Day 71
Overall Antibody Titer Levels by Visit
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.
Time frame: Day 1 - Day 71
Presence of Neutralizing Antibody (Seropositivity) at Day 71 (LOCF) by Antidrug Antibody Log Titer Quartiles
Q1 and Q4 are based on the ADA titer levels.
Time frame: Day 71

Results

Posted Oct 8, 2020

Participant flow

Participant flow — Overall Study
Milestone	Collagenase Clostridium Histolyticum (CCH)	Placebo
Started	214	208
Completed	186	191
Not completed	28	17
Withdrew: Lost to follow-up	11	5
Withdrew: Withdrawal by subject	9	7
Withdrew: Adverse event	8	2
Withdrew: Protocol violation	0	3

Outcome measures

Primary2-level Composite Responders for the Target Buttock

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.

Time frame:: Day 71
Reported as:: Count of participants · Participants

2-level Composite Responders for the Target Buttock
Participants	Collagenase Clostridium Histolyticum (CCH)	Placebo
Yes	12	1
No	202	205

Statistical analysis

Collagenase Clostridium Histolyticum (CCH) vs Placebo · Cochran-Mantel-Haenszel · p = 0.002Adjusted for analysis center

Secondary1-level PR-PCSS Responders of the Target Buttock

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).

Time frame:: Day 71
Reported as:: Count of participants · Participants

1-level PR-PCSS Responders of the Target Buttock
Participants	Collagenase Clostridium Histolyticum (CCH)	Placebo
Yes	124	61
No	90	145

Statistical analysis

Collagenase Clostridium Histolyticum (CCH) vs Placebo · Cochran-Mantel-Haenszel · p = <0.001Adjusted for analysis center

Secondary2-level PR-PCSS Responders of the Target Buttock

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).

Time frame:: Day 71
Reported as:: Count of participants · Participants

2-level PR-PCSS Responders of the Target Buttock
Participants	Collagenase Clostridium Histolyticum (CCH)	Placebo
Yes	45	12
No	169	194

Statistical analysis

Collagenase Clostridium Histolyticum (CCH) vs Placebo · Cochran-Mantel-Haenszel · p = <0.001Adjusted for analysis center

Secondary1-level Composite Responders of the Target Buttock

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).

Time frame:: Day 71
Reported as:: Count of participants · Participants

1-level Composite Responders of the Target Buttock
Participants	Collagenase Clostridium Histolyticum (CCH)	Placebo
Yes	89	23
No	125	183

Statistical analysis

Collagenase Clostridium Histolyticum (CCH) vs Placebo · Cochran-Mantel-Haenszel · p = <0.001Adjusted for analysis center

Secondary2-level Composite Responders of the Non-target Buttock

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).

Time frame:: Day 71
Reported as:: Count of participants · Participants

2-level Composite Responders of the Non-target Buttock
Participants	Collagenase Clostridium Histolyticum (CCH)	Placebo
Yes	13	4
No	201	202

Statistical analysis

Collagenase Clostridium Histolyticum (CCH) vs Placebo · Cochran-Mantel-Haenszel · p = 0.033Adjusted for analysis center

Secondary1-level SSRS Responders

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.

Time frame:: Day 71
Reported as:: Count of participants · Participants

1-level SSRS Responders
Participants	Collagenase Clostridium Histolyticum (CCH)	Placebo
1-level SSRS Responders	90	31

Statistical analysis

Collagenase Clostridium Histolyticum (CCH) vs Placebo · Cochran-Mantel-Haenszel · p = <0.001Adjusted for analysis center

SecondaryChange From Baseline in PR-CIS Total Score

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.

Time frame:: Day 71
Reported as:: Mean · score on a scale

Change From Baseline in PR-CIS Total Score
score on a scale	Collagenase Clostridium Histolyticum (CCH)	Placebo
Baseline (Day 1)	52.4 ± 8.01	51.6 ± 9.40
Day 71	40.9 ± 13.57	45.1 ± 12.65
Change from Baseline	-11.5 ± 12.74	-6.5 ± 11.74

Statistical analysis

Collagenase Clostridium Histolyticum (CCH) vs Placebo · ANCOVA · p = <0.001With factors of treatment group and analysis center adjusted for baseline values in the model

Secondary1-level S-GAIS Responders of Target Buttock

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.

Time frame:: Day 71
Reported as:: Count of participants · Participants

1-level S-GAIS Responders of Target Buttock
Participants	Collagenase Clostridium Histolyticum (CCH)	Placebo
1-level S-GAIS Responders of Target Buttock	126	46

Statistical analysis

Collagenase Clostridium Histolyticum (CCH) vs Placebo · Cochran-Mantel-Haenszel · p = <0.001Adjusted for analysis center

Secondary2-level S-GAIS Responders of Target Buttock

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.

Time frame:: Day 71
Reported as:: Count of participants · Participants

2-level S-GAIS Responders of Target Buttock
Participants	Collagenase Clostridium Histolyticum (CCH)	Placebo
2-level S-GAIS Responders of Target Buttock	38	9

Statistical analysis

Collagenase Clostridium Histolyticum (CCH) vs Placebo · Cochran-Mantel-Haenszel · p = <0.001Adjusted for analysis center

SecondaryPR-PCSS Rating for the Target and Non-target Buttock by Visit

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).

Time frame:: Day 71
Reported as:: Count of participants · Participants

PR-PCSS Rating for the Target and Non-target Buttock by Visit
Participants	Day 1: CCH	Day 1: Placebo	Day 22: CCH	Day 22: Placebo	Day 43: CCH	Day 43: Placebo	Day 71: CCH	Day 71: Placebo	Day 71: CCH (LOCF)	Day 71: Placebo (LOCF)
Target Buttock Rating — None (0)	0	0	0	1	0	0	3	0	3	0
Target Buttock Rating — Almost None (1)	0	0	1	1	17	3	19	2	19	2
Target Buttock Rating — Mild (2)	0	0	45	17	61	26	61	32	64	32
Target Buttock Rating — Moderate (3)	89	82	78	79	67	85	65	76	76	81
Target Buttock Rating — Severe (4)	120	119	73	101	41	77	38	81	47	86
Non-target Buttock Rating — None (0)	0	0	0	1	0	0	1	0	1	0
Non-target Buttock Rating — Almost None (1)	0	0	3	0	17	4	21	3	21	3
Non-target Buttock Rating — Mild (2)	0	0	38	19	55	24	58	32	64	34
Non-target Buttock Rating — Moderate (3)	96	71	82	71	67	86	66	72	74	75
Non-target Buttock Rating — Severe (4)	113	130	74	108	47	77	40	84	49	89

SecondarySubjects Satisfaction With Cellulite Treatment

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.

Time frame:: Day 71
Reported as:: Count of participants · Participants

Subjects Satisfaction With Cellulite Treatment
Participants	Day 71: CCH	Day 71: Placebo	Day 71: CCH (LOCF)	Day 71: Placebo (LOCF)
Very Satisfied (+2)	15	4	15	4
Satisfied (+1)	72	22	74	22
Neither Satisfied Nor Dissatisfied (0)	60	73	64	75
Dissatisfied (-1)	24	47	29	48
Very Dissatisfied (-2)	15	45	16	46

Other pre-specifiedSerum Antibody Positivity by Visit

Percent of participants that are seropositive. Percentages were based on the number of subjects who had immunogenicity lab samples analyzed at the visit.

Time frame:: Day 1 - Day 71
Reported as:: Count of participants · Participants

Serum Antibody Positivity by Visit
Participants	Anti-AUX-I: CCH	Anti-AUX-I: Placebo	Anti-AUX-II: CCH	Anti-AUX-II: Placebo
Day 1 — Seropositive	6	2	3	6
Day 1 — Seronegative	208	204	211	200
Day 22 — Seropositive	106	1	52	7
Day 22 — Seronegative	90	198	144	192
Day 43 — Seropositive	183	4	183	7
Day 43 — Seronegative	3	186	3	183
Day 71 — Seropositive	186	8	185	9
Day 71 — Seronegative	0	182	1	181

Other pre-specifiedOverall Antibody Titer Levels by Visit

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.

Time frame:: Day 1 - Day 71
Reported as:: Mean · log 10 titer

Overall Antibody Titer Levels by Visit
log 10 titer	Anti-AUX-I: CCH	Anti-AUX-I: Placebo	Anti-AUX-II: CCH	Anti-AUX-II: Placebo
Day 1 positive	2.235 ± 1.7365	1.000 ± 0.0000	3.212 ± 0.8056	1.365 ± 0.3834
Day 22 positive	2.331 ± 1.2566	3.504	1.912 ± 1.2718	1.387 ± 0.4788
Day 43 positive	4.602 ± 0.8721	2.539 ± 1.1462	3.680 ± 1.0617	1.302 ± 0.4596
Day 71 positive	5.898 ± 0.7131	2.039 ± 1.2854	5.255 ± 0.7142	1.572 ± 0.7895

Other pre-specifiedPresence of Neutralizing Antibody (Seropositivity) at Day 71 (LOCF) by Antidrug Antibody Log Titer Quartiles

Q1 and Q4 are based on the ADA titer levels.

Time frame:: Day 71
Reported as:: Count of participants · Participants

Presence of Neutralizing Antibody (Seropositivity) at Day 71 (LOCF) by Antidrug Antibody Log Titer Quartiles
Participants	CCH: Q1	CCH: Q4	CCH: Total
Neutralizing AUX-I Antibody — Negative	12	3	15
Neutralizing AUX-I Antibody — Positive	12	21	33
Neutralizing AUX-II Antibody — Negative	5	1	6
Neutralizing AUX-II Antibody — Positive	19	23	42

Adverse events

Collected over All (serious and nonserious) AEs, from Day 1 to Day 71. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Collagenase Clostridium Histolyticum (CCH)	0/214 (0%)	1/214 (0.5%)	203/214 (94.9%)
Placebo	0/206 (0%)	0/206 (0%)	64/206 (31.1%)

Most frequent serious events

Most frequent serious events
Event	Collagenase Clostridium Histolyticum (CCH)	Placebo
SyncopeNervous system disorders	1/214	0/206
HypotensionVascular disorders	1/214	0/206
HypokalemiaMetabolism and nutrition disorders	1/214	0/206

Most frequent other events

Most frequent other events
Event	Collagenase Clostridium Histolyticum (CCH)	Placebo
Injection site bruisingGeneral disorders	193/214	42/206
Injection site painGeneral disorders	127/214	26/206
Injection site noduleGeneral disorders	70/214	2/206
Injection site pruritusGeneral disorders	34/214	3/206
Injection site erythemaGeneral disorders	28/214	17/206
Injection site discolourationGeneral disorders	21/214	2/206
Injection site massGeneral disorders	15/214	0/206
Injection site warmthGeneral disorders	13/214	0/206

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Collagenase Clostridium Histolyticum (CCH)	Placebo	Total
Mean	47.7 ± 10.62	45.7 ± 11.16	46.7 ± 10.92

Sex: Female, Male
Sex: Female, Male(Participants)	Collagenase Clostridium Histolyticum (CCH)	Placebo	Total
Female	214	206	420
Male	0	0	0

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Collagenase Clostridium Histolyticum (CCH)	Placebo	Total
Hispanic or Latino	46	58	104
Not Hispanic or Latino	168	148	316
Unknown or Not Reported	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Collagenase Clostridium Histolyticum (CCH)	Placebo	Total
American Indian or Alaska Native	3	5	8
Asian	0	1	1
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	29	32	61
White	179	164	343
More than one race	2	2	4
Unknown or Not Reported	1	2	3

Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)	Collagenase Clostridium Histolyticum (CCH)	Placebo	Total
Mean	30.52 ± 6.184	31.14 ± 7.567	30.82 ± 6.896

Skin Category (Fitzpatrick Scale)
Skin Category (Fitzpatrick Scale)(Participants)	Collagenase Clostridium Histolyticum (CCH)	Placebo	Total
I (Pale White)	6	8	14
II (Fair)	74	54	128
III (Darker White)	50	64	114
IV (Light Brown)	53	47	100
V (Brown)	15	18	33
VI (Dark Brown)	16	15	31

Study locations

25 sites

Endo Clinical Trial Site #1
Glendale, Arizona 85308, United States
Endo Clinical Trial Site #2
North Little Rock, Arkansas 72116, United States
Endo Clinical Trial Site #3
Beverly Hills, California 90210, United States
Endo Clinical Trial Site #4
Murrieta, California 92562, United States
Endo Clinical Trial Site #5
Newport Beach, California 92663, United States
Endo Clinical Trial Site #6
San Diego, California 92121, United States
Endo Clinical Trial Site #7
Greenwood Village, Colorado 80111, United States
Endo Clinical Trial Site #8
Coral Gables, Florida 33146, United States
Endo Clinical Trial Site #9
Miami, Florida 33137, United States
Endo Clinical Trial Site #10
Nampa, Idaho 83651, United States
Endo Clinical Trial Site #11
Carmel, Indiana 46032, United States
Endo Clinical Trial Site #12
Metairie, Louisiana 70006, United States
Endo Clinical Trial Site #13
New Orleans, Louisiana 70124, United States
Endo Clinical Trial Site #14
Warren, Michigan 48088, United States
Endo Clinical Trial Site #15
Montclair, New Jersey 07042, United States
Endo Clinical Trial Site #16
East Setauket, New York 11733, United States
Endo Clinical Trial Site #17
New York, New York 10016, United States
Endo Clinical Trial Site #18
Cincinnati, Ohio 45212, United States
Endo Clinical Trial Site #19
Nashville, Tennessee 37215, United States
Endo Clinical Trial Site #20
Austin, Texas 78759, United States
Endo Clinical Trial Site #21
Beaumont, Texas 77701, United States
Endo Clinical Trial Site #22
Houston, Texas 77494, United States
Endo Clinical Trial Site #23
San Antonio, Texas 78229, United States
Endo Clinical Trial Site #24
Salt Lake City, Utah 84101, United States
Endo Clinical Trial Site #25
Lynchburg, Virginia 24501, United States

References and documents

Publications

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. PubMed 33840781 ↗

Study documents

Protocol and statistical analysis plan · Jun 5, 2018

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

Registry details

Key details

Study ID: NCT03446781
Lead sponsor: Endo Pharmaceuticals
Responsible party: Sponsor
First posted: Feb 27, 2018
Start date: Feb 8, 2018
Primary completion: Sep 26, 2018
Completion: Sep 26, 2018
Results posted: Oct 8, 2020
Last update: Oct 8, 2020

Study contacts

Michael McLane

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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This study is completed, as verified in Sep 2020. You cannot join it, but the record below documents what was studied.

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