Safety and Pharmacokinetics of a Single Dose of CCH (3.36 mg) in Subjects With EFP
Condition: Edematous Fibrosclerotic Panniculopathy
MeSH terms: Edema
Intervention: CCH (collagenase clostridium histolyticum)
Intervention description: A single dose of 3.36 mg of CCH will be administered as subcutaneous injections (CCH 0.84 mg) per quadrant concurrently in 4 quadrants. A quadrant is defined as one of the following: left buttock, right buttock, left posterolateral thigh, or right posterolateral thigh.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Cellulite; Edematous Fibrosclerotic Panniculopathy; EFP

Summary:

      This study will evaluate the safety and Pharmacokinetics (PK) of a single 3.36-mg dose of
      Collagenase Clostridium Histolyticum (CCH) in 4 quadrants concurrently, in subjects with
      Edematous fibrosclerotic panniculopathy (EFP).

      This study will provide insight to the PK profile and safety of concurrent subcutaneous
      injections of CCH 0.84 mg/quadrant into 4 quadrants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  No subject will be dosed until all eligibility criteria have been satisfied. In order
             to be eligible to participate in the study, subjects must meet the following criteria:

               1. Be a female ≥18 years of age.

               2. Have evidence of cellulite within 4 quadrants (a quadrant is defined as a left
                  buttock, right buttock, left posterolateral thigh or right posterolateral thigh)
                  as assessed by the Investigator using the Clinician-Reported Photonumeric
                  Cellulite Severity Scale (CR-PCSS) at the Screening visit; has a score of 2
                  (mild), 3 (moderate) or 4 (severe) as reported by the Investigator (CR-PCSS) in 4
                  quadrants at the Screening visit.

               3. Have a body mass index (BMI) between 20.0 and 35.0 kg/m^2, and intends to
                  maintain stable body weight throughout the duration of the study (a variation of
                  ≤10% from baseline body weight is permitted).

               4. Be willing to apply sunscreen to the dosing quadrants 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 pregnancy test at the Screening visit and on Day -1 at admission
                  (before injection of study drug); and be using an effective contraception method
                  (e.g., abstinence, intrauterine device [IUD], hormonal [estrogen/progestin]
                  contraceptives, or double barrier control) for at least 1 menstrual cycle prior
                  to study enrollment and for the duration of the study; or be menopausal defined
                  as 12 months of amenorrhea in the absence of other biological or physiological
                  causes, as determined by the Investigator; or post-menopausal for at least 1
                  year; or be surgically sterile (i.e., hysterectomy, bilateral oophorectomy, tubal
                  ligation).

               7. Be willing and able to cooperate with the requirements of the study.

               8. Voluntarily sign and date an informed consent form approved by the Institutional
                  Review Board/Independent Ethics Committee/Human Research Ethics Committee
                  (IRB/IEC/HREC).

        Exclusion Criteria:

          -  A subject will be excluded from study participation if she:

               1. 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.

               2. 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 (e.g., varicose veins) in areas to be treated

                    3. Inflammation or active infection

                    4. Active cutaneous alteration including rash, eczema, psoriasis, or skin
                       cancer

                    5. Has a tattoo located within 2 cm of the site of injection

               3. Requires the following concomitant medications before or during participation in
                  the trial:

                  a. Anticoagulant or antiplatelet medication or has received anticoagulant or
                  antiplatelet medication (except for ≤150 mg aspirin daily) within 7 days before
                  injection of study drug

               4. Has a positive test on a urine drug screen for drugs of abuse

               5. Has a history of drug or alcohol abuse

               6. Has used any of the following for the treatment of EFP on the legs or buttock
                  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 quadrants during the 12-month period before
                       injection of study drug

                    2. Injections (e.g., mesotherapy); radiofrequency device treatments; laser
                       treatment; or surgery (including subcision and/or powered subcision) within
                       the treatment quadrants during the 12-month period before injection of study
                       drug

                    3. Endermologie or similar treatments within the treatment quadrants during the
                       6-month period before injection of study drug

                    4. Massage therapy within the treatment quadrants during the 3-month period
                       before injection of study drug

                    5. Creams (e.g., Celluvera™, TriLastin®) to prevent or mitigate EFP within the
                       treatment quadrants during the 2-week period before injection of study drug

               7. Is presently nursing a baby or providing breast milk for a baby

               8. Intends to become pregnant during the study

               9. Intends to initiate an intensive sport or exercise program during the study

              10. Intends to initiate a weight reduction program during the study

              11. Has received an investigational drug or treatment within 30 days before injection
                  of study drug

              12. Has a known systemic allergy to collagenase or any other excipient of study drug

              13. Has received any collagenase treatments at any time prior to treatment

              14. Has been a subject in a previous cellulite clinical trial of CCH: AUX-CC-830,
                  AUX-CC-831, EN3835-102, EN3835-104, EN3835-201, EN3835-202, EN3835-205,
                  EN3835-302, EN3835-303, EN3835-304, and/or EN3835-209.