Safety and Tolerability of Collagenase Clostridium Histolyticum (EN3835) to Treat Uterine Leiomyoma (Fibroids)

This is an interventional treatment trial for Fibroids, Uterine Read More

Inclusion Criteria:

• Parous and non-parous women who have completed child-bearing (age criteria of > 35 years-old, and <50 years-old)
• Currently practicing or willing to practice contraception throughout the duration of the study
• Women with at least one or two fibroids greater than or equal to 3 cm diameter, and less than or equal to 10 cm diameter for subjects in Group 1, and at least one fibroid greater than or equal to 3 cm diameter, and less than or equal to 10 cm diameter for subjects in Group 2
• Fibroids will be intramural fibroids which will be surrounded by a layer of myometrium. Fibroids must be well visualized on ultrasound examination and provide a clear path for injection
• Women who were planning to undergo abdominal hysterectomy or myomectomy for treatment of symptomatic fibroids. Subjects must be willing to defer the operation until 24-96 hours after study treatment for Group 1 and for 60-90 days after study treatment for Group 2. The patients will understand that they may choose to have surgery or any other non-study treatment at any time after enrollment and end study participation
• "Typical" large fibroids visualized as hypo-intense on a T2-weighted MRI scan

Exclusion Criteria:

• Inability to understand study procedures or to comply with study visits and requirements
• BMI > 40kg/m2
• History of allergic reaction to study medication (Collagenase Clostridium Histolyticum) or any components of the study drug
• Inability to undergo hysterectomy or myomectomy
• Inability to tolerate MRI and transvaginal ultrasound procedures (i.e. presence of an intra-uterine device (IUD), pacemakers, aneurismal clips or other metallic devices that are not compatible with magnetic resonance imaging). However women with IUD's compatible with MRI are eligible for the study
• Medical problems including: genetic diseases that cause fibroids, history of thromboembolic (blood clot) events or need for anticoagulation (Coumadin, Heparin, etc.) Subjects taking or planning to take anti-coagulant medication (except for ≤ 150 mg aspirin daily) within 7 days administration study drug and within 7 days before and after hysterectomy
• A history of cancer within the past 5 years
• Abnormal liver function tests (typically, will be >20% elevation). Mild elevations will be at the discretion of the investigators, but undiagnosed liver conditions will represent an exclusion criterion
• Pregnancy or lactation. Pregnancy will be evaluated by urine test every 30 days if necessary. Patients will be asked to use non-hormonal contraception methods while in this study
• Severe anemia (hematocrit <30). Mild anemia is common in women with fibroids
• Recent rapid growth of fibroids (i.e. doubling in size within one-six months period)
• Any use of agents like Imidazoles, due to possible interference with metabolism
• Unevaluated gynecologic abnormalities (unexplained vaginal bleeding, cervical dysplasia, or abnormal adnexal/ovarian mass)
• Fibroids that are visualized on T2 and T1 weighted MRI as hyperdense or show cystic degeneration
• Inability to undergo injection of fibroid with study drug for any reason, anatomic or other
• Has a known systemic allergy to collagenase or any other excipient of EN3835 or any other procedural medication
• Has, at any time, received collagenase as a treatment
• Is planning to be treated with commercial XIAFLEX at any time during the study
• Type 0 submucosal fibroids, submucosal fibroids with significant protrusion/ pedunculation and subserosal fibroids are not appropriate candidates for the injections