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

NCT03632993 | Completed Phase 2 Results FDA Drug

• 1 other identifier: EN3835-209
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 5

Brief 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).

Conditions

Edematous Skin

Keywords

Edematous Fibrosclerotic Panniculopathy; Cellulite; Collagenase Clostridium Histolyticum

Outcome Measures

Primary Outcomes (6)

• 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).

  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).

  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).

  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)

  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)

  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)

  Baseline, Day 71

Secondary Outcomes (1)

• Change From Baseline of Dimple Volume by Treatment Region

  Baseline, Day 22, Day 43, and Day 71

Study Arms (5)

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).

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).

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).

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).

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).

Drug: collagenase clostridium histolyticum (CCH)

Interventions

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.

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

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Endo Pharmaceuticals: lead

Study Sites (5)

Endo Clinical Trial Site #1

Coral Gables, Florida, 33146, United States

Location

Endo Clinical Trial Site #5

Miami, Florida, 33137, United States

Location

Endo Clinical Trial Site #2

New York, New York, 10016, United States

Location

Endo Clinical Trial Site #4

New York, New York, 10022, United States

Location

Endo Clinical Trial Site #3

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Cellulite

Interventions

Microbial Collagenase

Condition Hierarchy (Ancestors)

Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Collagenases; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases

Results Point of Contact

• Title: Clinical Operations
• Organization: Endo Pharmaceuticals

clinicaltrials@endo.com

800-462-3636

Study Officials

• George Omburo

  Endo Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2018
• First Posted: August 16, 2018
• Study Start: September 18, 2018
• Primary Completion: January 24, 2019
• Study Completion: January 24, 2019
• Last Updated: September 7, 2023
• Results First Posted: September 7, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

US (5)