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

• ClinicalTrials.gov Identifier: NCT03632993
• Recruitment Status: Completed
• First Posted: August 16, 2018
• Last Update Posted: February 5, 2020
• Sponsor: Endo Pharmaceuticals
• Information provided by (Responsible Party): Endo Pharmaceuticals

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Edematous Skin	Drug: collagenase clostridium histolyticum (CCH)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 64 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: September 18, 2018
• Actual Primary Completion Date: January 24, 2019
• Actual Study Completion Date: January 24, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Treatment I: CCH Shallow Injection, 3 Aliquots; In Treatment I, CCH will be injected subcutaneously while the subject lies in a prone position. Each injection will consist of a single skin injection of study drug administered as three 0.1 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 subject per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area).	Drug: 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 (e.g., dermal septa) at the site of injection and does not require systemic exposure to be effective.
Active Comparator: Treatment II: CCH Shallow Injection, 1 Aliquot; In Treatment II, CCH will be injected subcutaneously while the subject 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 subject per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area).	Drug: 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 (e.g., dermal septa) at the site of injection and does not require systemic exposure to be effective.
Active Comparator: Treatment III: CCH Deep Injection, 1 Aliquot; In Treatment III, CCH will be injected subcutaneously while the subject 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 subject per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area).	Drug: 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 (e.g., dermal septa) at the site of injection and does not require systemic exposure to be effective.
Active Comparator: Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots; In Treatment IV, CCH will be injected subcutaneously while the subject 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 1.5mL of CCH (5 aliquots of 0.3 mL, for each injection, in each syringe). Dose per subject per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area).	Drug: 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 (e.g., dermal septa) at the site of injection and does not require systemic exposure to be effective.
Active Comparator: Treatment V: CCH Shallow Injections, 4 Aliquots; In Treatment V, CCH will be injected subcutaneously while the subject 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 1.2mL of CCH (4 aliquots of 0.3mL each). Dose per subject per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area).	Drug: 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 (e.g., dermal septa) at the site of injection and does not require systemic exposure to be effective.

Outcome Measures

Primary Outcome Measures :

1. The aesthetic appearance improvement from baseline in the 3-D photographic image using the Likert Scale score of aesthetic appearance. [ Time Frame: 71 Days: Subjects who complete the study will participate for up to 92 days including a 21 day screening period, a 43 day active treatment period, and a 28 day follow-up period. ]
   Change from baseline in the Likert Scale score of aesthetic.
2. The change from baseline in the Hexsel CSS (B) depression depth scale [ Time Frame: 71 Days: Subjects who complete the study will participate for up to 92 days including a 21 day screening period, a 43 day active treatment period, and a 28 day follow-up period. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

No subject will be assigned to treatment until all eligibility criteria have been satisfied. To qualify for the study a subject must:

1. 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).
2. Be female and at least 18 years of age at the time of consent.

3. 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:

   1. 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.

   2. has at least 2 dimples from each treatment area that:

      • are isolated and separated by at least 5 cm from any other dimples.
      • score 2 or 3 on the Hexsel depression scale.
      • have dimple width: length ratio ≥ 0.5.
4. Be willing to apply sunscreen to the dosing areas before each exposure to the sun while participating in the study (ie, screening through end of study).
5. Be judged to be in good health, based upon the results of a medical history, physical examination, and laboratory profile at screening.
6. 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 (e.g., 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).
7. Be willing and able to comply with all protocol required study visits and assessments.

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from the study:

1. Is pregnant or is intending to become pregnant during the study.
2. Is presently nursing/breastfeeding or providing breast milk.

3. 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.

4. 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).
   3. Inflammation or active infection.
   4. Severe skin laxity, flaccidity, and/or sagging.
   5. Active cutaneous alteration including rash, eczema, psoriasis, or skin cancer.
5. Has a tattoo located within 2 cm of the site of injection.
6. 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.

7. 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:

   1. Liposuction within the treatment areas during the 12-month period before injection of study drug.
   2. Injections (eg, 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.
   3. Any investigational treatment for EFP/cellulite on treatment areas during the 12-month period before the injection of study drug.
   4. Endermologie® or similar treatments within the treatment areas during the 6-month period before injection of study drug.
   5. Massage therapy within the treatment areas during the 3-month period before injection of study drug.
   6. Creams (eg, Celluvera™, TriLastin®) to prevent or mitigate EFP within the treatment areas during the 2-week period before injection of study drug.
8. Has received an investigational drug or treatment within 30 days before injection of study drug.
9. Has a known systemic allergy to collagenase or any other excipient of study drug.
10. Has a history of drug or alcohol abuse.
11. Intends to initiate an intensive sport or exercise program during the study.
12. Intends to initiate a weight reduction program during the study.
13. Intends to use tanning spray or tanning booths during the study.
14. Has previously received any collagenase treatments (eg, Santyl® ointment and/or XIAFLEX/XIAPEX®).
15. Was a subject 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.
16. Any other condition(s) that, in the Investigator's opinion, might indicate the subject is unsuitable for the study.

Contacts and Locations

Locations

United States, Florida

Endo Clinical Trial Site #1

Coral Gables, Florida, United States, 33146

Endo Clinical Trial Site #5

Miami, Florida, United States, 33137

United States, New York

Endo Clinical Trial Site #2

New York, New York, United States, 10016

Endo Clinical Trial Site #4

New York, New York, United States, 10022

Endo Clinical Trial Site #3

New York, New York, United States, 10065

Sponsors and Collaborators

Endo Pharmaceuticals

Investigators

• Study Director: George Omburo; Endo Pharmaceuticals

More Information

• Responsible Party: Endo Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03632993
• Other Study ID Numbers: EN3835-209
• First Posted: August 16, 2018
• Last Update Posted: February 5, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Endo Pharmaceuticals:

Edematous Fibrosclerotic Panniculopathy; Cellulite; Collagenase Clostridium Histolyticum

Additional relevant MeSH terms:

Edema