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NCT03428750: RELEASE-1

Effectiveness and Safety of EN3835 in the Treatment of EFP (Cellulite) in Women

Completed Phase 3 Results posted Last updated 8 October 2020
What this trial tests

Phase 3 trial testing EN3835 in Edematous Fibrosclerotic Panniculopathy (Cellulite) in 423 participants. Completed in 26 September 2018.

Timeline
5 February 2018
Primary endpoint
26 September 2018
26 September 2018

Quick facts

Lead sponsorEndo Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment423
Start date5 February 2018
Primary completion26 September 2018
Estimated completion26 September 2018
Sites26 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Endo Pharmaceuticals — full company profile →

Who can join

18 and older, female only, with Edematous Fibrosclerotic Panniculopathy (Cellulite). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

2-level Composite Responders for the Target Buttock Primary · Day 71

Number of 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 participant who missed one or two assessments of CR-PCSS and PR-PCSS at Day 71 was defined as a non-responder. A 2-level composite responder is defined as a participant with an 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 s

GroupValue95% CI
Collagenase Clostridium Histolyticum (CCH)16
Placebo4
Collagenase Clostridium Histolyticum (CCH)194
Placebo209
1-level PR-PCSS Responders of the Target Buttock Secondary · 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).

GroupValue95% CI
Collagenase Clostridium Histolyticum (CCH)114
Placebo77
Collagenase Clostridium Histolyticum (CCH)96
Placebo136
2-level PR-PCSS Responders of the Target Buttock Secondary · Day 71

Improvement in cellulite severity of the Target Buttock from baseline of at least 2-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).

GroupValue95% CI
Collagenase Clostridium Histolyticum (CCH)51
Placebo26
Collagenase Clostridium Histolyticum (CCH)159
Placebo187
1-level Composite Responders of the Target Buttock Secondary · 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).

GroupValue95% CI
Collagenase Clostridium Histolyticum (CCH)78
Placebo38
Collagenase Clostridium Histolyticum (CCH)132
Placebo175
2-level Composite Responder of the Non-target Buttock Secondary · 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).

GroupValue95% CI
Collagenase Clostridium Histolyticum (CCH)16
Placebo2
Collagenase Clostridium Histolyticum (CCH)194
Placebo211
1-level SSRS Responders Secondary · 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.

GroupValue95% CI
Collagenase Clostridium Histolyticum (CCH)102
Placebo48
Change From Baseline in PR-CIS Total Score Secondary · 71 Days

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 was defined as a participant with a reduction in the PR-CIS total score of at least 12 from baseline at an evaluation time point. A negative change from baseline indicates an improvement in cellulite severity.

Baseline (Day 1)
GroupValue95% CI
Collagenase Clostridium Histolyticum (CCH)51.1± 8.86
Placebo51.6± 9.77
Day 71
GroupValue95% CI
Collagenase Clostridium Histolyticum (CCH)40.2± 13.27
Placebo45.7± 12.93
Change from Baseline
GroupValue95% CI
Collagenase Clostridium Histolyticum (CCH)-10.9± 12.51
Placebo-5.9± 11.62
1-level S-GAIS Responders of Target Buttock Secondary · 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 at least ≥ 1-level improvement (Improved, Much Improved or Very Much Improved) in S-GAIS assessment of the Target Buttock.

GroupValue95% CI
Collagenase Clostridium Histolyticum (CCH)135
Placebo82
2-level S-GAIS Responders of Target Buttock Secondary · 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 at least ≥ 2-level improvement (Much Improved or Very Much Improved) in S-GAIS assessment of the Target Buttock.

GroupValue95% CI
Collagenase Clostridium Histolyticum (CCH)49
Placebo13
PR-PCSS Rating for the Target and Non-target Buttock by Visit Secondary · Day 1 to 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 scale ratings range from "0" (None) to "4" (Severe).

Target Buttock Rating
GroupValue95% CI
Day 1: CCH0
Day 1: Placebo0
Day 22: CCH0
Day 22: Placebo0
Day 43: CCH0
Day 43: Placebo1
Day 71: CCH0
Day 71: Placebo2
Day 71: CCH (LOCF)0
Day 71: Placebo (LOCF)2
Day 1: CCH0
Day 1: Placebo0
Day 22: CCH1
Day 22: Placebo0
Day 43: CCH13
Day 43: Placebo4
Day 71: CCH25
Day 71: Placebo5
Day 71: CCH (LOCF)25
Day 71: Placebo (LOCF)5
Day 1: CCH0
Day 1: Placebo0
Day 22: CCH29
Day 22: Placebo7
Day 43: CCH50
Day 43: Placebo24
Day 71: CCH54
Day 71: Placebo38
Day 71: CCH (LOCF)58
Day 71: Placebo (LOCF)40
Day 1: CCH84
Day 1: Placebo82
Day 22: CCH79
Day 22: Placebo95
Day 43: CCH75
Day 43: Placebo95
Day 71: CCH65
Day 71: Placebo77
Day 71: CCH (LOCF)72
Day 71: Placebo (LOCF)81
Nontarget Buttock Rating
GroupValue95% CI
Day 1: CCH0
Day 1: Placebo0
Day 22: CCH0
Day 22: Placebo0
Day 43: CCH1
Day 43: Placebo1
Day 71: CCH1
Day 71: Placebo2
Day 71: CCH (LOCF)1
Day 71: Placebo (LOCF)2
Day 1: CCH0
Day 1: Placebo0
Day 22: CCH2
Day 22: Placebo0
Day 43: CCH12
Day 43: Placebo4
Day 71: CCH20
Day 71: Placebo7
Day 71: CCH (LOCF)21
Day 71: Placebo (LOCF)7
Day 1: CCH0
Day 1: Placebo0
Day 22: CCH27
Day 22: Placebo9
Day 43: CCH50
Day 43: Placebo33
Day 71: CCH55
Day 71: Placebo34
Day 71: CCH (LOCF)59
Day 71: Placebo (LOCF)35
Day 1: CCH81
Day 1: Placebo83
Day 22: CCH81
Day 22: Placebo89
Day 43: CCH80
Day 43: Placebo82
Day 71: CCH63
Day 71: Placebo88
Day 71: CCH (LOCF)70
Day 71: Placebo (LOCF)93
Subjects Satisfaction With Cellulite Treatment at Day 71 Secondary · 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.

GroupValue95% CI
Day 71: CCH24
Day 71: Placebo7
Day 71: CCH (LOCF)24
Day 71: Placebo (LOCF)7
Day 71: CCH76
Day 71: Placebo42
Day 71: CCH (LOCF)80
Day 71: Placebo (LOCF)42
Day 71: CCH46
Day 71: Placebo56
Day 71: CCH (LOCF)52
Day 71: Placebo (LOCF)56
Day 71: CCH23
Day 71: Placebo42
Day 71: CCH (LOCF)23
Day 71: Placebo (LOCF)42
Serum Antibody Positivity by Visit Secondary · 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.

Day 1
GroupValue95% CI
Anti-AUX-I: CCH12
Anti-AUX-I: Placebo5
Anti-AUX-II: CCH11
Anti-AUX-II: Placebo9
Anti-AUX-I: CCH197
Anti-AUX-I: Placebo207
Anti-AUX-II: CCH198
Anti-AUX-II: Placebo203
Day 22
GroupValue95% CI
Anti-AUX-I: CCH97
Anti-AUX-I: Placebo5
Anti-AUX-II: CCH49
Anti-AUX-II: Placebo9
Anti-AUX-I: CCH90
Anti-AUX-I: Placebo195
Anti-AUX-II: CCH138
Anti-AUX-II: Placebo191
Day 43
GroupValue95% CI
Anti-AUX-I: CCH186
Anti-AUX-I: Placebo6
Anti-AUX-II: CCH180
Anti-AUX-II: Placebo10
Anti-AUX-I: CCH2
Anti-AUX-I: Placebo188
Anti-AUX-II: CCH8
Anti-AUX-II: Placebo184
Day 71
GroupValue95% CI
Anti-AUX-I: CCH185
Anti-AUX-I: Placebo10
Anti-AUX-II: CCH185
Anti-AUX-II: Placebo12
Anti-AUX-I: CCH0
Anti-AUX-I: Placebo182
Anti-AUX-II: CCH0
Anti-AUX-II: Placebo180

Adverse events — posted to ClinicalTrials.gov

Time frame: All (serious and nonserious) AEs, from Day 1 to Day 71. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Collagenase Clostridium Histolyticum (CCH)
Serious: 0/210 (0%)
Deaths: 0/210
Placebo
Serious: 1/213 (0%)
Deaths: 0/213

Serious adverse events (1 terms)

ReactionSystemCollagenase Clostridium Hi…Placebo
Colitis ischaemicGastrointestinal disorders
Other adverse events (8 terms — click to expand)

ReactionSystemCollagenase Clostridium Hi…Placebo
Injection site bruisingGeneral disorders
Injection site painGeneral disorders
Injection stie noduleGeneral disorders
Injection site pruritusGeneral disorders
Injection site haemorrhageGeneral disorders
Injection site massGeneral disorders
Injection site swellingGeneral disorders
Injection site discolourationGeneral disorders

Most-reported serious reactions: Colitis ischaemic.

Data from ClinicalTrials.gov NCT03428750 adverse events section.

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Collagenase Clostridium Histolyticum-aaes for the Treatment of Cellulite in Women: Results From Two Phase 3 Randomized, Placebo-Controlled Trials.
    Kaufman-Janette J, Joseph JH, Kaminer MS, Clark J, et al · · 2021 · cited 26× · PMID 33840781 · DOI 10.1097/dss.0000000000002952
  2. Development and Validation Clinician and Patient Reported Photonumeric Scales to Assess Buttocks Cellulite Severity.
    Cohen JL, Sadick NS, Kirby MT, McLane MP, et al · · 2020 · cited 13× · PMID 33009069 · DOI 10.1097/dss.0000000000002756
  3. Efficacy, Safety, and Durability of Response of Collagenase Clostridium Histolyticum-aaes for Treating Cellulite.
    Kaufman-Janette JA, Bass LS, Xiang Q, McLane MP, et al · · 2020 · cited 11× · PMID 33425621 · DOI 10.1097/gox.0000000000003316
  4. Collagenase Clostridium Histolyticum-aaes for Treatment of Cellulite: A Pooled Analysis of Two Phase-3 Trials.
    Bass LS, Kaufman-Janette J, Joseph JH, Kaminer MS, et al · · 2022 · cited 10× · PMID 35646496 · DOI 10.1097/gox.0000000000004306

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing