Edematous SkinPhase 2NCT03632993

Injection Techniques of Collagenase Clostridium Histolyticum (CCH) for the Treatment of EFP (Cellulite)

A Phase 2 study testing collagenase clostridium histolyticum (CCH) in people with Edematous Skin, run by Endo USA Inc., a Keenova Therapeutics Company at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The study will evaluate the safety and effectiveness of different injection techniques of Collagenase Clostridium Histolyticum (CCH) for the treatment of adult women with mild, moderate or severe Edematous Fibrosclerotic Panniculopathy (commonly known as Cellulite). Read more about this study

Who is it for?: Ages 18 years and older, women onlyHealthy volunteers can take part
Conditions the study is for: Edematous Skin
What is being tested?: collagenase clostridium histolyticum (CCH)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 64 participants
Where: 5 sitesUnited States
Study dates: 18 Sep 2018to 24 Jan 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

No participant will be assigned to treatment until all eligibility criteria have been satisfied. To qualify for the study a participant must:
Be able to provide voluntary written informed consent prior to the initiation of any study specific procedures per the policy of the governing Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
Be female and at least 18 years of age at the time of consent.
Have evidence of cellulite in 2 bilateral treatment areas (defined as right and left buttocks or right and left posterolateral thighs) as assessed by the Investigator at the Screening visit, and fulfills the following requirements:
has a score of 2 (mild), 3 (moderate) or 4 (severe) as reported by the Investigator (CR-PCSS) in 2 treatment areas (two thighs or two buttocks) at the Screening Visit.
has at least 2 dimples from each treatment area that:

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are isolated and separated by at least 5 centimeters (cm) from any other dimples.
score 2 or 3 on the Hexsel depression scale.
have dimple width: length ratio ≥ 0.5.
Be willing to apply sunscreen to the dosing areas before each exposure to the sun while participating in the study (that is, 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 the Screening Visit and negative urine pregnancy at Day 1 (before injection of study drug), be using an effective contraception method (for example, abstinence, intrauterine device, hormonal [estrogen/progestin] contraceptives, or double barrier control) for at least 1 menstrual cycle prior to study enrollment and through Day 71; or be menopausal defined as at least 12 months of amenorrhea in the absence of other biological or physiological causes (as determined by the Investigator), or be post-menopausal for at least 1 year, or be surgically sterile (hysterectomy, bilateral oophorectomy, bilateral tubal ligation).
Be willing and able to comply with all protocol required study visits and assessments.

Who cannot join

Participants who meet any of the following criteria will be excluded from the study:
Is pregnant or is intending to become pregnant during the study.
Is presently nursing/breastfeeding or providing breast milk.
Has any of the following systemic conditions:
Coagulation disorder.
Evidence or history of malignancy (other than excised basal-cell carcinoma) unless there has been no recurrence in at least 5 years.

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History of keloidal scarring or abnormal wound healing.
Concurrent diseases or conditions that might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the participant's well-being.
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:
History of lower extremity thrombosis or post-thrombosis syndrome.
Vascular disorder (for example, varicose veins, telangiectasia).
Inflammation or active infection.
Severe skin laxity, flaccidity, and/or sagging.
Active cutaneous alteration including rash, eczema, psoriasis, or skin cancer.
Has a tattoo located within 2 cm of the site of injection.
Requires anticoagulant or antiplatelet medication during the study 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 the area to be treated within the timelines identified below or intends to use any of the following at any time during the course of the study:
Liposuction within the treatment areas during the 12-month period before injection of study drug.
Injections (for example, mesotherapy); radiofrequency device treatments; laser treatment; or surgery (including subcision and/or powered subcision) within the treatment areas during the 12-month period before injection of study drug.
Any investigational treatment for EFP/cellulite on treatment areas during the 12-month period before the injection of study drug.
Endermologie® or similar treatments within the treatment areas during the 6-month period before injection of study drug.
Massage therapy within the treatment areas during the 3-month period before injection of study drug.
Creams (for example, Celluvera™, TriLastin®) to prevent or mitigate EFP within the treatment areas during the 2-week period before injection of study drug.
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 a history of drug or alcohol abuse.
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 previously received any collagenase treatments (for example, Santyl® ointment and/or XIAFLEX/XIAPEX®).
Was a participant in a previous cellulite clinical trial of EN3835: AUX-CC-830, AUX-CC-831, EN3835-102, EN3835-104, EN3835-201, EN3835-202, EN3835-205, EN3835-302, or EN3835-303.
Any other condition(s) that, in the Investigator's opinion, might indicate the participant is unsuitable for the study.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Endo Clinical Trial Site #1
Coral Gables, Florida, 33146
Endo Clinical Trial Site #5
Miami, Florida, 33137
Endo Clinical Trial Site #2
New York, New York, 10016
Endo Clinical Trial Site #4
New York, New York, 10022
Endo Clinical Trial Site #3
New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase 2A, Open-Label Study Evaluating the Safety and Different Injection Techniques of CCH for the Treatment of Edematous Fibrosclerotic Panniculopathy (EFP)

Conditions: Edematous Skin
Being tested: collagenase clostridium histolyticum (CCH)
Keywords: Edematous Fibrosclerotic Panniculopathy, Cellulite, Collagenase Clostridium Histolyticum
Medical subject headings: Cellulite

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

collagenase clostridium histolyticum (CCH)Drug
Endo Pharmaceuticals Inc. (Endo) is developing collagenase clostridium histolyticum (CCH) for the treatment of EFP. Because CCH is a proteinase that can hydrolyze the triple-helical region of collagen under physiological conditions, CCH has the potential to be effective in lysing sub-dermal collagen, such as those observed in the dermal septa, which are the underlying cause of the skin dimpling in women with Edematous Fibrosclerotic Panniculopathy (EFP). CCH targets the collagenase structural matrix (for example, dermal septa) at the site of injection and does not require systemic exposure to be effective.

Study groups in NCT03632993
Study group	Role	What they receive
Treatment I: CCH Shallow Injection, 3 Aliquots	Active comparator	In Treatment I, CCH will be injected subcutaneously while the participant lies in a prone position. Each injection will consist of a single skin injection of study drug administered as three 0.1 milliliters (mL) aliquots (for a total injection volume of 0.3 mL). During each treatment visit, 8 syringes (4 syringes per treatment area) will be prepared for dosing. Each syringe will contain 0.9 mL of CCH (3 injections in each syringe). Dose per participant per treatment visit = up to 1.68 milligrams (mg) of CCH (0.84 mg in each treatment area). Receives: Drug: collagenase clostridium histolyticum (CCH)
Treatment II: CCH Shallow Injection, 1 Aliquot	Active comparator	In Treatment II, CCH will be injected subcutaneously while the participant is in a prone position. Each injection will consist of a single skin injection of study drug administered as a single shallow injection of a 0.3 mL aliquot. During each treatment visit, 8 syringes (4 syringes per treatment area) will be prepared for dosing. Each syringe will contain 0.9 mL of CCH (3 injections in each syringe). Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area). Receives: Drug: collagenase clostridium histolyticum (CCH)
Treatment III: CCH Deep Injection, 1 Aliquot	Active comparator	In Treatment III, CCH will be injected subcutaneously while the participant is in a prone position. Each injection will consist of a single skin injection of study drug administered as a single deep injection of a 0.3 mL study drug aliquot. During each treatment visit, 8 syringes (4 syringes per treatment area) will be prepared for dosing. Each syringe will contain 0.9 mL of CCH (3 injections in each syringe). Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area). Receives: Drug: collagenase clostridium histolyticum (CCH)
Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots	Active comparator	In Treatment IV, CCH will be injected subcutaneously while the participant lies in a prone position. Each injection will consist of a single skin injection of study drug administered as five 0.3 mL (for a total injection volume of 1.5 mL). During each treatment visit, 24 syringes (12 syringes per treatment area) will be prepared for dosing. Each syringe will contain 1.5 mL of CCH (5 aliquots of 0.3 mL, for each injection, in each syringe). Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area). Receives: Drug: collagenase clostridium histolyticum (CCH)
Treatment V: CCH Shallow Injections, 4 Aliquots	Active comparator	In Treatment V, CCH will be injected subcutaneously while the participant lies in a prone position. Each injection will receive a single skin injection of study drug administered as four 0.3 mL aliquots (for a total injection volume of 1.2 mL). During each treatment visit, 24 syringes (12 syringes per treatment area) will be prepared for dosing. Each syringe will contain 1.2 mL of CCH (4 aliquots of 0.3 mL each). Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area). Receives: Drug: collagenase clostridium histolyticum (CCH)

What is being measured

The primary outcome is the main question the study is designed to answer.

Aesthetic Appearance Improvement Likert Scores by Treatment Region at Day 22
Aesthetic appearance improvement for each treatment area (buttocks or thighs) was assessed by a blinded central assessment, using a 5-point Likert scale with scores ranging from -1 to 3. Aesthetic improvement was scored as worse (-1), stayed the same (0), improved (1), much improved (2) and very much improved (3). The assessor evaluated the image at Day 22 in comparison with baseline and recorded the Likert score. Aesthetic appearance Likert scale scores were analyzed using linear mixed model with treatment arm, study visit, interaction of treatment arm and study visit as fixed effects. This model was fitted using the response for the average of left and right of treatment area (that is, average of left buttock and right buttock or average of left thigh and right thigh).
Measured: Day 22
Aesthetic Appearance Improvement Likert Scores by Treatment Region at Day 43
Aesthetic appearance improvement for each treatment area (buttocks or thighs) was assessed by a blinded central assessment, using a 5-point Likert scale with scores ranging from -1 to 3. Aesthetic improvement was scored as worse (-1), stayed the same (0), improved (1), much improved (2) and very much improved (3). The assessor evaluated the image at Day 43 in comparison with baseline and recorded the Likert score. Aesthetic appearance Likert scale scores were analyzed using linear mixed model with treatment arm, study visit, interaction of treatment arm and study visit as fixed effects. This model was fitted using the response for the average of left and right of treatment area (that is, average of left buttock and right buttock or average of left thigh and right thigh).
Measured: Day 43
Aesthetic Appearance Improvement Likert Scores by Treatment Region at Day 71
Aesthetic appearance improvement for each treatment area (buttocks or thighs) was assessed by a blinded central assessment, using a 5-point Likert scale with scores ranging from -1 to 3. Aesthetic improvement was scored as worse (-1), stayed the same (0), improved (1), much improved (2) and very much improved (3). The assessor evaluated the image at Day 71 in comparison with baseline and recorded the Likert score. Aesthetic appearance Likert scale scores were analyzed using linear mixed model with treatment arm, study visit, interaction of treatment arm and study visit as fixed effects. This model was fitted using the response for the average of left and right of treatment area (that is, average of left buttock and right buttock or average of left thigh and right thigh).
Measured: Day 71
Change From Baseline in Dimple Depth Depression (Hexsel CSS [B]) by Treatment Region at Day 22
Dimple depth depression for each treatment area was assessed by the Investigator using the Hexsel Cellulite Severity Scale (B). Dimple Depth Depression of Hexsel Cellulite Severity Scale (B) was assessed and graded as: no depression (0), superficial depressions (1), medium depth depressions (2) and deep depressions (3). A negative change in Hexsel CSS (B) from baseline indicated an improvement in depression depth. Change from Baseline in dimple depth depression of Hexsel Cellulite Severity Scale (B) was analyzed using linear mixed model with treatment arm, study visits, interaction of treatment arm and study visit as fixed effect. This model was fitted using the response for the average of left and right of treatment areas (that is, average of left buttock and right buttock; average of left thigh and right thigh)
Measured: Baseline, Day 22
Change From Baseline in Dimple Depth Depression (Hexsel CSS [B]) by Treatment Region at Day 43
Dimple depth depression for each treatment area was assessed by the Investigator using the Hexsel Cellulite Severity Scale (B). Dimple Depth Depression of Hexsel Cellulite Severity Scale (B) was assessed and graded as: no depression (0), superficial depressions (1), medium depth depressions (2) and deep depressions (3). A negative change in Hexsel CSS (B) from baseline indicated an improvement in depression depth. Change from Baseline in dimple depth depression of Hexsel Cellulite Severity Scale (B) was analyzed using linear mixed model with treatment arm, study visits, interaction of treatment arm and study visit as fixed effect. This model was fitted using the response for the average of left and right of treatment areas (that is, average of left buttock and right buttock; average of left thigh and right thigh)
Measured: Baseline, Day 43
Change From Baseline in Dimple Depth Depression (Hexsel CSS [B]) by Treatment Region at Day 71
Dimple depth depression for each treatment area was assessed by the Investigator using the Hexsel Cellulite Severity Scale (B). Dimple Depth Depression of Hexsel Cellulite Severity Scale (B) was assessed and graded as: no depression (0), superficial depressions (1), medium depth depressions (2) and deep depressions (3). A negative change in Hexsel CSS (B) from baseline indicated an improvement in depression depth. Change from Baseline in dimple depth depression of Hexsel Cellulite Severity Scale (B) was analyzed using linear mixed model with treatment arm, study visits, interaction of treatment arm and study visit as fixed effect. This model was fitted using the response for the average of left and right of treatment areas (that is, average of left buttock and right buttock; average of left thigh and right thigh)
Measured: Baseline, Day 71

Secondary outcomes (1)

Change From Baseline of Dimple Volume by Treatment Region
For each treated buttock and thigh, 4 dimple parameters including the maximum length (largest straight line distance across the dimple), maximum width (largest straight line distance perpendicular to the maximum length measurement), surface are, and volume (between the base of the dimple and an interpolated surface) of the target dimple were assessed. A negative change from Day 1 indicated an improvement. Volume of Dimple from Day 1 pre-marking was analyzed using linear mixed model with treatment arm, study visit, interaction of treatment arm and study visit as fixed effects. This model was fitted using the measurement for the average of left and right of treatment areas (that is, average of left buttock posterior and right buttock posterior; average of left thigh lateral, left thigh oblique, left thigh posterior, right thigh lateral, right thigh oblique, and right thigh posterior).
Measured: Baseline, Day 22, Day 43, and Day 71

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Sep 201824 Jan 2019

First posted16 Aug 2018
Study start18 Sep 2018
Primary completion24 Jan 2019
Study completion24 Jan 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Edematous SkinStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 64 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03632993
Sponsor's protocol ID: EN3835-209
Status last verified: Aug 2023
First submitted: 5 Jul 2018
Last updated: 7 Sep 2023
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes

Study at a glance

From the registry record, last updated by the sponsor on 7 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2A, Open-Label Study Evaluating the Safety and Different Injection Techniques of CCH for the Treatment of Edematous Fibrosclerotic Panniculopathy (EFP)
ClinicalTrials.gov ID: NCT03632993
Acronym / sponsor ID: EN3835-209
Conditions: Edematous Skin
Keywords: Edematous Fibrosclerotic Panniculopathy, Cellulite, Collagenase Clostridium Histolyticum
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 64 participants (actual)
Lead sponsor: Endo USA Inc., a Keenova Therapeutics CompanyIndustry (pharma, biotech, devices)
Study start: 18 Sep 2018 (actual)
Primary completion: 24 Jan 2019 (actual)
Study completion: 24 Jan 2019 (actual)
First posted: 16 Aug 2018 (actual)
Results: Posted 7 Sep 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Treatment I: CCH Shallow Injection, 3 Aliquots	Active comparator	Drug: collagenase clostridium histolyticum (CCH)In Treatment I, CCH will be injected subcutaneously while the participant lies in a prone position. Each injection will consist of a single skin injection of study drug administered as three 0.1 milliliters (mL) aliquots (for a total injection volume of 0.3 mL). During each treatment visit, 8 syringes (4 syringes per treatment area) will be prepared for dosing. Each syringe will contain 0.9 mL of CCH (3 injections in each syringe). Dose per participant per treatment visit = up to 1.68 milligrams (mg) of CCH (0.84 mg in each treatment area).
Treatment II: CCH Shallow Injection, 1 Aliquot	Active comparator	Drug: collagenase clostridium histolyticum (CCH)In Treatment II, CCH will be injected subcutaneously while the participant is in a prone position. Each injection will consist of a single skin injection of study drug administered as a single shallow injection of a 0.3 mL aliquot. During each treatment visit, 8 syringes (4 syringes per treatment area) will be prepared for dosing. Each syringe will contain 0.9 mL of CCH (3 injections in each syringe). Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area).
Treatment III: CCH Deep Injection, 1 Aliquot	Active comparator	Drug: collagenase clostridium histolyticum (CCH)In Treatment III, CCH will be injected subcutaneously while the participant is in a prone position. Each injection will consist of a single skin injection of study drug administered as a single deep injection of a 0.3 mL study drug aliquot. During each treatment visit, 8 syringes (4 syringes per treatment area) will be prepared for dosing. Each syringe will contain 0.9 mL of CCH (3 injections in each syringe). Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area).
Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots	Active comparator	Drug: collagenase clostridium histolyticum (CCH)In Treatment IV, CCH will be injected subcutaneously while the participant lies in a prone position. Each injection will consist of a single skin injection of study drug administered as five 0.3 mL (for a total injection volume of 1.5 mL). During each treatment visit, 24 syringes (12 syringes per treatment area) will be prepared for dosing. Each syringe will contain 1.5 mL of CCH (5 aliquots of 0.3 mL, for each injection, in each syringe). Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area).
Treatment V: CCH Shallow Injections, 4 Aliquots	Active comparator	Drug: collagenase clostridium histolyticum (CCH)In Treatment V, CCH will be injected subcutaneously while the participant lies in a prone position. Each injection will receive a single skin injection of study drug administered as four 0.3 mL aliquots (for a total injection volume of 1.2 mL). During each treatment visit, 24 syringes (12 syringes per treatment area) will be prepared for dosing. Each syringe will contain 1.2 mL of CCH (4 aliquots of 0.3 mL each). Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area).

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

No participant will be assigned to treatment until all eligibility criteria have been satisfied. To qualify for the study a participant must:
Be able to provide voluntary written informed consent prior to the initiation of any study specific procedures per the policy of the governing Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
Be female and at least 18 years of age at the time of consent.
Have evidence of cellulite in 2 bilateral treatment areas (defined as right and left buttocks or right and left posterolateral thighs) as assessed by the Investigator at the Screening visit, and fulfills the following requirements:
Be willing to apply sunscreen to the dosing areas before each exposure to the sun while participating in the study (that is, screening through end of study).

Key exclusion criteria (33 listed)

Is pregnant or is intending to become pregnant during the study.
Is presently nursing/breastfeeding or providing breast milk.
Has any of the following systemic conditions:
Has any of the following local conditions in the areas to be treated:
Has a tattoo located within 2 cm of the site of injection.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
collagenase clostridium histolyticum (CCH)Endo Pharmaceuticals Inc. (Endo) is developing collagenase clostridium histolyticum (CCH) for the treatment of EFP. Because CCH is a proteinase that can hydrolyze the triple-helical region of collagen under physiological conditions, CCH has the potential to be effective in lysing sub-dermal collagen, such as those observed in the dermal septa, which are the underlying cause of the skin dimpling in women with Edematous Fibrosclerotic Panniculopathy (EFP). CCH targets the collagenase structural matrix (for example, dermal septa) at the site of injection and does not require systemic exposure to be effective.	Drug	Treatment I: CCH Shallow Injection, 3 Aliquots, Treatment II: CCH Shallow Injection, 1 Aliquot, Treatment III: CCH Deep Injection, 1 Aliquot, Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots, Treatment V: CCH Shallow Injections, 4 Aliquots

Primary outcome

Aesthetic Appearance Improvement Likert Scores by Treatment Region at Day 22
Time frame: Day 22
Aesthetic appearance improvement for each treatment area (buttocks or thighs) was assessed by a blinded central assessment, using a 5-point Likert scale with scores ranging from -1 to 3. Aesthetic improvement was scored as worse (-1), stayed the same (0), improved (1), much improved (2) and very much improved (3). The assessor evaluated the image at Day 22 in comparison with baseline and recorded the Likert score. Aesthetic appearance Likert scale scores were analyzed using linear mixed model with treatment arm, study visit, interaction of treatment arm and study visit as fixed effects. This model was fitted using the response for the average of left and right of treatment area (that is, average of left buttock and right buttock or average of left thigh and right thigh).
Aesthetic Appearance Improvement Likert Scores by Treatment Region at Day 43
Time frame: Day 43
Aesthetic appearance improvement for each treatment area (buttocks or thighs) was assessed by a blinded central assessment, using a 5-point Likert scale with scores ranging from -1 to 3. Aesthetic improvement was scored as worse (-1), stayed the same (0), improved (1), much improved (2) and very much improved (3). The assessor evaluated the image at Day 43 in comparison with baseline and recorded the Likert score. Aesthetic appearance Likert scale scores were analyzed using linear mixed model with treatment arm, study visit, interaction of treatment arm and study visit as fixed effects. This model was fitted using the response for the average of left and right of treatment area (that is, average of left buttock and right buttock or average of left thigh and right thigh).
Aesthetic Appearance Improvement Likert Scores by Treatment Region at Day 71
Time frame: Day 71
Aesthetic appearance improvement for each treatment area (buttocks or thighs) was assessed by a blinded central assessment, using a 5-point Likert scale with scores ranging from -1 to 3. Aesthetic improvement was scored as worse (-1), stayed the same (0), improved (1), much improved (2) and very much improved (3). The assessor evaluated the image at Day 71 in comparison with baseline and recorded the Likert score. Aesthetic appearance Likert scale scores were analyzed using linear mixed model with treatment arm, study visit, interaction of treatment arm and study visit as fixed effects. This model was fitted using the response for the average of left and right of treatment area (that is, average of left buttock and right buttock or average of left thigh and right thigh).
Change From Baseline in Dimple Depth Depression (Hexsel CSS [B]) by Treatment Region at Day 22
Time frame: Baseline, Day 22
Dimple depth depression for each treatment area was assessed by the Investigator using the Hexsel Cellulite Severity Scale (B). Dimple Depth Depression of Hexsel Cellulite Severity Scale (B) was assessed and graded as: no depression (0), superficial depressions (1), medium depth depressions (2) and deep depressions (3). A negative change in Hexsel CSS (B) from baseline indicated an improvement in depression depth. Change from Baseline in dimple depth depression of Hexsel Cellulite Severity Scale (B) was analyzed using linear mixed model with treatment arm, study visits, interaction of treatment arm and study visit as fixed effect. This model was fitted using the response for the average of left and right of treatment areas (that is, average of left buttock and right buttock; average of left thigh and right thigh)
Change From Baseline in Dimple Depth Depression (Hexsel CSS [B]) by Treatment Region at Day 43
Time frame: Baseline, Day 43
Dimple depth depression for each treatment area was assessed by the Investigator using the Hexsel Cellulite Severity Scale (B). Dimple Depth Depression of Hexsel Cellulite Severity Scale (B) was assessed and graded as: no depression (0), superficial depressions (1), medium depth depressions (2) and deep depressions (3). A negative change in Hexsel CSS (B) from baseline indicated an improvement in depression depth. Change from Baseline in dimple depth depression of Hexsel Cellulite Severity Scale (B) was analyzed using linear mixed model with treatment arm, study visits, interaction of treatment arm and study visit as fixed effect. This model was fitted using the response for the average of left and right of treatment areas (that is, average of left buttock and right buttock; average of left thigh and right thigh)
Change From Baseline in Dimple Depth Depression (Hexsel CSS [B]) by Treatment Region at Day 71
Time frame: Baseline, Day 71
Dimple depth depression for each treatment area was assessed by the Investigator using the Hexsel Cellulite Severity Scale (B). Dimple Depth Depression of Hexsel Cellulite Severity Scale (B) was assessed and graded as: no depression (0), superficial depressions (1), medium depth depressions (2) and deep depressions (3). A negative change in Hexsel CSS (B) from baseline indicated an improvement in depression depth. Change from Baseline in dimple depth depression of Hexsel Cellulite Severity Scale (B) was analyzed using linear mixed model with treatment arm, study visits, interaction of treatment arm and study visit as fixed effect. This model was fitted using the response for the average of left and right of treatment areas (that is, average of left buttock and right buttock; average of left thigh and right thigh)

1 secondary outcome

Change From Baseline of Dimple Volume by Treatment Region
Time frame: Baseline, Day 22, Day 43, and Day 71

Results and safety

Results posted to the registry on 7 Sep 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment I: CCH Shallow Injection, 3 Aliquots (Buttocks)	7	6
Treatment I: CCH Shallow Injection, 3 Aliquots (Thighs)	6	5
Treatment II: CCH Shallow Injection, 1 Aliquot (Buttocks)	6	6
Treatment II: CCH Shallow Injection, 1 Aliquot (Thighs)	7	7
Treatment III: CCH Deep Injection, 1 Aliquot (Buttocks)	6	6
Treatment III: CCH Deep Injection, 1 Aliquot (Thighs)	6	4
Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots (Buttocks)	6	6
Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots (Thighs)	7	5
Treatment V: CCH Shallow Injections, 4 Aliquots (Buttocks)	7	7
Treatment V: CCH Shallow Injections, 4 Aliquots (Thighs)	6	5

Primary outcome: Aesthetic Appearance Improvement Likert Scores by Treatment Region at Day 22

Time frame: Day 22. Least squares mean (95% Confidence Interval). Unit: score on a scale

Measure	Treatment I: CCH Shallow Injection, 3 Aliquots (Buttocks) n = 6	Treatment I: CCH Shallow Injection, 3 Aliquots (Thighs) n = 5	Treatment II: CCH Shallow Injection, 1 Aliquot (Buttocks) n = 6	Treatment II: CCH Shallow Injection, 1 Aliquot (Thighs) n = 7	Treatment III: CCH Deep Injection, 1 Aliquot (Buttocks) n = 6	Treatment III: CCH Deep Injection, 1 Aliquot (Thighs) n = 5	Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots (Buttocks) n = 6	Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots (Thighs) n = 6	Treatment V: CCH Shallow Injections, 4 Aliquots (Buttocks) n = 7	Treatment V: CCH Shallow Injections, 4 Aliquots (Thighs) n = 5
Value	1.08 (0.51 to 1.65)	1.10 (0.46 to 1.74)	0.75 (0.18 to 1.32)	0.50 (-0.04 to 1.04)	0.67 (0.10 to 1.24)	0.20 (-0.44 to 0.84)	0.83 (0.26 to 1.40)	0.67 (0.09 to 1.25)	1.00 (0.47 to 1.53)	1.10 (0.46 to 1.74)

Population analysed: Evaluable Population includes all participants in the Safety Population who had completed screening procedures and at least 1 baseline assessment of aesthetic appearance improvement Likert scale rating at specified timepoint. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for the assessment.

Primary outcome: Aesthetic Appearance Improvement Likert Scores by Treatment Region at Day 43

Time frame: Day 43. Least squares mean (95% Confidence Interval). Unit: score on a scale

Measure	Treatment I: CCH Shallow Injection, 3 Aliquots (Buttocks) n = 6	Treatment I: CCH Shallow Injection, 3 Aliquots (Thighs) n = 5	Treatment II: CCH Shallow Injection, 1 Aliquot (Buttocks) n = 5	Treatment II: CCH Shallow Injection, 1 Aliquot (Thighs) n = 7	Treatment III: CCH Deep Injection, 1 Aliquot (Buttocks) n = 6	Treatment III: CCH Deep Injection, 1 Aliquot (Thighs) n = 5	Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots (Buttocks) n = 6	Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots (Thighs) n = 6	Treatment V: CCH Shallow Injections, 4 Aliquots (Buttocks) n = 7	Treatment V: CCH Shallow Injections, 4 Aliquots (Thighs) n = 5
Value	0.75 (0.18 to 1.32)	1.40 (0.76 to 2.04)	1.10 (0.47 to 1.73)	0.57 (0.03 to 1.11)	1.00 (0.43 to 1.57)	-0.01 (-0.64 to 0.64)	1.17 (0.60 to 1.74)	0.42 (-0.16 to 1.00)	1.21 (0.69 to 1.74)	0.70 (0.06 to 1.34)

Primary outcome: Aesthetic Appearance Improvement Likert Scores by Treatment Region at Day 71

Time frame: Day 71. Least squares mean (95% Confidence Interval). Unit: score on a scale

Measure	Treatment I: CCH Shallow Injection, 3 Aliquots (Buttocks) n = 6	Treatment I: CCH Shallow Injection, 3 Aliquots (Thighs) n = 6	Treatment II: CCH Shallow Injection, 1 Aliquot (Buttocks) n = 6	Treatment II: CCH Shallow Injection, 1 Aliquot (Thighs) n = 7	Treatment III: CCH Deep Injection, 1 Aliquot (Buttocks) n = 6	Treatment III: CCH Deep Injection, 1 Aliquot (Thighs) n = 4	Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots (Buttocks) n = 6	Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots (Thighs) n = 5	Treatment V: CCH Shallow Injections, 4 Aliquots (Buttocks) n = 7	Treatment V: CCH Shallow Injections, 4 Aliquots (Thighs) n = 5
Value	1.08 (0.51 to 1.65)	0.92 (0.34 to 1.50)	1.08 (0.51 to 1.65)	0.43 (-0.11 to 0.97)	1.00 (0.43 to 1.57)	0.12 (-0.59 to 0.84)	0.50 (-0.07 to 1.07)	0.30 (-0.34 to 0.94)	1.29 (0.76 to 1.81)	0.60 (-0.04 to 1.24)

Primary outcome: Change From Baseline in Dimple Depth Depression (Hexsel CSS [B]) by Treatment Region at Day 22

Time frame: Baseline, Day 22. Least squares mean (95% Confidence Interval). Unit: score on a scale

Measure	Treatment I: CCH Shallow Injection, 3 Aliquots (Buttocks) n = 6	Treatment I: CCH Shallow Injection, 3 Aliquots (Thighs) n = 5	Treatment II: CCH Shallow Injection, 1 Aliquot (Buttocks) n = 6	Treatment II: CCH Shallow Injection, 1 Aliquot (Thighs) n = 7	Treatment III: CCH Deep Injection, 1 Aliquot (Buttocks) n = 6	Treatment III: CCH Deep Injection, 1 Aliquot (Thighs) n = 5	Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots (Buttocks) n = 6	Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots (Thighs) n = 6	Treatment V: CCH Shallow Injections, 4 Aliquots (Buttocks) n = 7	Treatment V: CCH Shallow Injections, 4 Aliquots (Thighs) n = 5
Value	-0.83 (-1.28 to -0.39)	-0.30 (-0.84 to 0.24)	-0.17 (-0.61 to 0.28)	-0.43 (-0.89 to 0.03)	-0.17 (-0.61 to 0.28)	-0.20 (-0.74 to 0.34)	-0.83 (-1.28 to -0.39)	-0.67 (-1.16 to -0.17)	-0.14 (-0.56 to 0.27)	-0.20 (-0.74 to 0.34)

Population analysed: Evaluable Population includes all participants in the Safety Population who had completed screening procedures and at least 1 baseline assessment of aesthetic appearance Likert scale rating at specified timepoint. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for the assessment.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Day 1 (after dosing) through Day 71. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment I: CCH Shallow Injection, 3 Aliquots (Buttocks)	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Treatment I: CCH Shallow Injection, 3 Aliquots (Thighs)	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Treatment II: CCH Shallow Injection, 1 Aliquot (Buttocks)	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Treatment II: CCH Shallow Injection, 1 Aliquot (Thighs)	0 of 7 (0%)	7 of 7 (100%)	0 of 7
Treatment III: CCH Deep Injection, 1 Aliquot (Buttocks)	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Treatment III: CCH Deep Injection, 1 Aliquot (Thighs)	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots (Buttocks)	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots (Thighs)	1 of 7 (14.3%)	7 of 7 (100%)	0 of 7
Treatment V: CCH Shallow Injections, 4 Aliquots (Buttocks)	1 of 7 (14.3%)	7 of 7 (100%)	0 of 7
Treatment V: CCH Shallow Injections, 4 Aliquots (Thighs)	0 of 6 (0%)	6 of 6 (100%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

George Omburo study director

Endo USA Inc., a Keenova Therapeutics Company

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing collagenase clostridium histolyticum (CCH) in people with Edematous Skin, run by Endo USA Inc., a Keenova Therapeutics Company at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Aesthetic Appearance Improvement Likert Scores by Treatment Region at Day 22 (time frame: Day 22). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03632993.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2023; AzTrials last refreshed its copy on 8 Nov 2026.