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

Endo Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Edematous Skin

Treatments: Drug: collagenase clostridium histolyticum (CCH)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03632993

EN3835-209

Details and patient eligibility

About

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).

Enrollment: 64 patients

Sex: Female

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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64 participants in 5 patient groups

Treatment I: CCH Shallow Injection, 3 Aliquots

Active Comparator group

Description:

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:

Drug: collagenase clostridium histolyticum (CCH)

Treatment II: CCH Shallow Injection, 1 Aliquot

Active Comparator group

Description:

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:

Drug: collagenase clostridium histolyticum (CCH)

Treatment III: CCH Deep Injection, 1 Aliquot

Active Comparator group

Description:

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:

Drug: collagenase clostridium histolyticum (CCH)

Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots

Active Comparator group

Description:

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:

Drug: collagenase clostridium histolyticum (CCH)

Treatment V: CCH Shallow Injections, 4 Aliquots

Active Comparator group

Description:

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).

Treatment:

Drug: collagenase clostridium histolyticum (CCH)