Injection Techniques of Collagenase Clostridium Histolyticum (CCH) for the Treatment of EFP (Cellulite)
Condition: Edematous Skin
MeSH terms: Edema
Intervention: collagenase clostridium histolyticum (CCH)
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 64.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Edematous Fibrosclerotic Panniculopathy; Cellulite; Collagenase Clostridium Histolyticum

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).
    

Eligibility criteria:

        Inclusion Criteria:

        No participant will be assigned to treatment until all eligibility criteria have been
        satisfied. To qualify for the study a participant 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 centimeters (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 (that is, 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 (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).

          7. Be willing and able to comply with all protocol required study visits and assessments.

        Exclusion Criteria:

        Participants 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
                  participant's well-being.

               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 (for example, 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 (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.

               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 (for example, 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 (for example, Santyl® ointment
             and/or XIAFLEX/XIAPEX®).

         15. 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.

         16. Any other condition(s) that, in the Investigator's opinion, might indicate the
             participant is unsuitable for the study.