EN3835 for the Treatment of Edematous Fibrosclerotic Panniculopathy (Commonly Known as Cellulite)

Study Overview
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Brief Summary
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A Phase 2, Open-Label Extension Study of EN3835 in the Treatment of Edematous Fibrosclerotic Panniculopathy (commonly known as Cellulite).

Official Title
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A Phase 2, Open-Label Extension Study of EN3835 in the Treatment of Edematous Fibrosclerotic Panniculopathy

Conditions
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Edematous Fibrosclerotic Panniculopathy, Cellulite

Intervention / Treatment
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* Biological: Collagenase Clostridium Histolyticum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Observation Phase: Voluntarily sign and date an informed consent agreement Have participated in and completed the double-blind study EN3835-201 Be willing to apply sunscreen to any treated quadrant before each exposure to sun Inclusion Criteria for Treatment Phase: Voluntarily sign and date an informed consent agreement Have participated in and completed the double-blind study EN3835-201 Be willing to apply sunscreen to any treated quadrant before each exposure to sun Have at least 1 quadrant with: a score of 3 or 4 (moderate or severe) as reported on the PCSS (Photonumeric Cellulite Severity Scale) by the subject or investigator, and a Hexsel CSS (Cellulite Severity Scale) score no greater than 13 Be judged to be in good health Have a negative urine pregnancy test at screening and be using an effective contraception method, be surgically sterile, or post-menopausal Exclusion Criteria for Observation Phase: None Exclusion Criteria for Treatment Phase: Has used, or intends to use during the course of the study, other treatment of EFP on the legs or buttocks Is presently nursing a baby or providing breast milk for a baby Intends to become pregnant during the study Currently receiving, has received within 7 days before injection of study drug, or plans to receive an anticoagulant or antiplatelet medication History of stroke or bleeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EN3835 Active<br>EN3835 0.84mg (Collagenase Clostridium Histolyticum) | Biological: Collagenase Clostridium Histolyticum<br> <br> * Other names: Xiaflex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Were 2-level Composite (CR-PCSS and PR-PCSS) Responders During the Observation Phase | Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) is a 5-level scale ranging from 0 (None) to 4 (Severe). A 2-level composite responder is a participant that received EN3835 with a reduction (decrease in score) in severity of at least 2-levels from baseline on both the CR-PCSS and the PR-PCSS at a particular visit. Observation Phase is defined as the time period from Screening to the first treatment date of the same treatment area in Study EN3835-202, or the end of Study EN3835-202 if there was no treatment received for the same treatment area in Study EN3835-202. Three participants were discontinued from the study after Day 180, percentages are based on the observed counts. | Day 180 to Day 360 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Were 1-level Composite (CR-PCSS and PR-PCSS) Responders During the Observation Phase | Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) is a 5-level scale ranging from 0 (None) to 4 (Severe). A 1-level composite responder is a participant that received EN3835 with a reduction (decrease in score) in severity of at least 1-level from baseline on both the PR-PCSS and the CR-PCSS at a particular visit. Observation Phase is defined as the time period from Screening to the first treatment date of the same treatment area in Study EN3835-202, or the end of Study EN3835-202 if there was no treatment received for the same treatment area in Study EN3835-202. | Day 180 to Day 360 | 
| Number of Participants That Were 2-level Composite (CR-PCSS and PR-PCSS) Responders During the Long-term Durability Phase | Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) is a 5-level scale ranging from 0 (None) to 4 (Severe). A 2-level composite responder is a participant that received EN3835 with a reduction (decrease in score) in severity of at least 2-levels from baseline on both the CR-PCSS and the PR-PCSS at a particular visit. Long-term Durability Phase is defined as all participants in the Overall Durability Population who showed an improvement on Day 71 of at least 1-level on each scale (CR-PCSS and PR-PCSS) from baseline for the treatment area treated with EN3835 in the double-blind Study (EN3835-201). | Day 540 to Day 720 | 
| Number of Participants That Were 1-level Composite (CR-PCSS and PR-PCSS) Responders During the Long-term Durability Phase | Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) is a 5-level scale ranging from 0 (None) to 4 (Severe). A 1-level composite responder is a participant who received EN3835 with a reduction (decrease in score) in severity of at least 1-level from baseline on both the PR-PCSS and the CR-PCSS at a particular visit. Long-term Durability Phase is defined as all participants in the Overall Durability Population who showed an improvement on Day 71 of at least 1-level on each scale (CR-PCSS and PR-PCSS) from baseline for the treatment area treated with EN3835 in the double-blind Study (EN3835-201). | Day 540 to Day 720 | 
| CR-PCSS Change From Baseline (in EN3835-201 Study) by Visit During the Observation Phase | Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) is a 5-level scale ranging from 0 (None) to 4 (Severe). A negative change from baseline indicates an improvement in cellulite severity. Observation Phase is defined as the time period from Screening to the first treatment date of the same treatment area in Study EN3835-202, or the end of Study EN3835-202 if there was no treatment received for the same treatment area in Study EN3835-202. | Baseline (in EN3835-201 Study) to Observation Day 360 | 
| CR-PCSS Change From Baseline (BL) by Visit During the Treatment Phase for Participants With a Second EN3835 Treatment | Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) is a 5-level scale ranging from 0 (None) to 4 (Severe). A decrease in the CR-PCSS score from baseline indicates an improvement in cellulite severity. Treatment phase is defined as the time period from the second EN3835 treatment date to the end of Study EN3835-202. One hundred sixty-two participants received a second treatment course Study EN3835-202 and were included in the Effectiveness Population. This retreated/redosed treatment group comprised 87 participants that received their second treatment course of EN3835 in Study EN3835-202 having received their first treatment course in Study EN3835-201 and 75 participants that received both their first and second treatment courses in Study EN3835-202. | Day 22 to Day 360 | 
| PR-PCSS Change From Baseline by Visit in Treatment Phase for Participants With Second EN3835 Treatment | Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) is a 5-level scale ranging from 0 (None) to 4 (Severe). A decrease in the PR-PCSS score from baseline indicates an improvement in cellulite severity. Treatment phase is defined as the time period from the second EN3835 treatment date to the end of Study EN3835-202. One hundred sixty-two participants received a second treatment course in this study and were included in the Effectiveness Population. This retreated/redosed treatment group comprised 87 participants that received their second treatment course of EN3835 in Study EN3835-202 having received their first treatment course in Study EN3835-201 and 75 participants that received both their first and second treatment courses in Study EN3835-202. | Day 22 to Day 360 | 
| Change From Baseline on the Hexsel CSS Total Score During the Observation Phase | The Hexsel Cellulite Severity Scale (CSS) is a photonumeric scale that evaluates 5 key morphologic features of cellulite: (A) number of evident depressions, (B) depth of depressions, (C) morphological appearance of skin surface alterations, (D) laxity, flaccidity or sagging of skin, and (E) current classification scale based on medical literature. Each of these features is evaluated on a 4-point scale from a low of 0 to a high of 3, with higher scores signifying more severe cellulite. The Hexcel CSS total score is the sum of all 5 features and can range from 0 (no cellulite) to 15 (extremely severe cellulite) and is designated in this study as the Hexsel CSS total score. | Baseline (in EN3835-201 Study) to Day 360 | 
| Change From Baseline (BL) in the Hexsel CSS Total Score During Long-term Durability Visits | The Hexsel Cellulite Severity Scale (CSS) is a photonumeric scale that evaluates 5 key morphologic features of cellulite: (A) number of evident depressions, (B) depth of depressions, (C) morphological appearance of skin surface alterations, (D) laxity, flaccidity or sagging of skin, and (E) current classification scale based on medical literature. Each of these features is evaluated on a 4-point scale from a low of 0 to a high of 3, with higher scores indicating more severe cellulite. The total score is a summation of all 5 features and can range from 0 (no cellulite) to 15 (extremely severe cellulite) and is designated in this study as the Hexsel CSS total score. A negative change from baseline indicates an improvement in cellulite severity. | Day 540 to Day 720 | 
| Change From Baseline in Hexsel CSS Total Score in Treatment Phase for Participants With Second EN3835 Treatment | The Hexsel Cellulite Severity Scale (CSS) is a photonumeric scale that evaluates 5 key morphologic features of cellulite: (A) number of evident depressions, (B) depth of depressions, (C) morphological appearance of skin surface alterations, (D) laxity, flaccidity or sagging of skin, and (E) current classification scale based on medical literature. Each of these features is evaluated on a 4-point scale from a low of 0 to a high of 3. The total score is a summation of all 5 features and can range from 0 (no cellulite) to 15 (extremely severe cellulite) and is designated in this study as the Hexsel CSS total score. Change from baseline is the visit total score minus baseline total score. A negative change from baseline indicates an improvement in cellulite severity. Treatment phase is defined as the time period from the second EN3835 treatment date to the end of Study EN3835-202. | Baseline - Day 360 | 
| Investigator Global Aesthetic Improvement Scale (I-GAIS) at Observation Visit Day 360 During the Observation Phase | Investigator Global Aesthetic Improvement Scale (I-GAIS) is a 7-point numeric scale that evaluates the improvement of the treated treatment area in global aesthetics. The scale ranges from +3 (Very much improved) to -3 (Very much worse), an increase in the I-GAIS scores indicates an improvement in Global Aesthetic Score. Percentages are based on the number of all evaluable subjects at each visit. Observation Phase is defined as the time period from Screening to the first treatment date of the same treatment area in Study EN3835-202, or the end of Study EN3835-202 if there was no treatment received for the same treatment area in Study EN3835-202. | Day 360 | 
| Investigator Global Aesthetic Improvement Scale (I-GAIS) in Treatment Phase for Participants With Second EN3835 Treatment | Investigator Global Aesthetic Improvement Scale (I-GAIS) is a 7-point numeric scale that evaluates the improvement of the treated treatment area in global aesthetics. The scale ranges from +3 (Very much improved) to -3 (Very much worse), an increase in the I-GAIS indicates an improvement in global aesthetics. Percentages are based on the number of all evaluable participants at each visit. One hundred sixty-two participants received a second treatment course in this study and were included in the Effectiveness Population. This retreated/dosed treatment group comprised 87 participants that received their second treatment course of EN3835 in Study EN3835-202 having received their first treatment course in Study EN3835-201 and 75 participants that received both their first and second treatment course in Study EN3835-202. | Day 71 - Day 360 | 
| Subject Global Aesthetic Improvement Scale (S-GAIS) at the End of Study (EOS) During the Observation Phase, Observation Visit Day 360 | Subject Global Aesthetic Improvement Scale (S-GAIS) is a 7-point numeric scale that evaluates the improvement of the treated treatment area in global aesthetics. The scale ranges from +3 (Very much improved) to -3 (Very much worse), an increase in S-GAIS indicates an improvement. Percentages are based on the number of all evaluable participants at each visit. Observation Phase is defined as the time period from Screening to the first treatment date of the same treatment area in Study EN3835-202, or the end of Study EN3835-202 if there was no treatment received for the same treatment area in Study EN3835-202. | Day 360 | 
| Subject Global Aesthetic Improvement Scale (S-GAIS) During the Treatment Phase for Participants With Second EN3835 Treatment | Subject Global Aesthetic Improvement Scale (S-GAIS) is a 7-point numeric scale that evaluates the improvement of the treated treatment area in global aesthetics. The scale ranges from +3 (Very much improved) to -3 (Very much worse). Percentages are based on the number of evaluable participants at each visit. One hundred sixty-two participants received a second treatment course in EN3835-202 Study and were included in the Effectiveness Population. This retreated/redosed treatment group comprised 87 participants that received their second treatment course of EN3835 in Study EN3835-202 having received their first treatment course in Study EN3835-201 and 75 participants that received both their first and second treatment courses in Study EN3835-202. Treatment phase is defined as the time period from the second EN3835 treatment date to the End of Study EN3835-202. | Day 71 - Day 360 | 
| Subject Satisfaction With EFP Treatment at the End of Study (EOS) in Observation Phase, Observation Visit Day 360 | Subject Satisfaction with Cellulite Treatment Scale is a 5-level scale designed for participants to assess their satisfaction with cellulite treatment. The scale ranges from +2 (I am very satisfied with the cellulite treatment on my buttocks or thighs) to -2 (I am very dissatisfied with the cellulite treatment on my buttocks or thighs). Percentages are based on the number of evaluable participants at each visit. Observation Phase is defined as the time period from Screening to the first treatment date of the same treatment area in Study EN3835-202, or the end of Study EN3835-202 if there was no treatment received for the same treatment area in Study EN3835-202. (EFP = Edematous Fibrosclerotic Panniculopathy, aka Cellulite) | Day 360 | 
| Subject Satisfaction With EFP Treatment in Treatment Phase for Subjects With Second EN3835 Treatment | Subject Satisfaction with Cellulite Treatment Scale is a 5-level scale designed for participants to assess their satisfaction with cellulite treatment. The scale ranges from +2 (I am very satisfied with the cellulite treatment on my buttocks or thighs) to -2 (I am very dissatisfied with the cellulite treatment on my buttocks or thighs). Percentages are based on the number of evaluable participants at each visit. One hundred sixty-two participants received a second treatment course in Study EN3835-202 and were included in the Effectiveness Population. This retreated/redosed treatment group comprised 87 participants that received their second treatment course of EN3835 in Study EN3835-202 having received their first treatment course in Study EN3835-201 and 75 participants that received both their first and second treatment courses in Study EN3835-202. Treatment phase is defined as the time period from the second EN3835 treatment date to the End of Study EN3835-202. | Day 71 - Day 360 |