Safety and Effectiveness of OCL 503 in the Treatment of Women With Leiomyomata

Study Overview
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Brief Summary
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This is a prospective, pilot, open-label, uncontrolled, safety and effectiveness study of uterine artery embolization with OCL 503 in women with leiomyomata who are scheduled for hysterectomy.

Detailed Description
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Patients will be allocated to Cohort 1 or Cohort 2. Following pelvic angiogram to delineate the uterine vasculature, embolization procedures of the left and right uterine arteries (as required) will be performed on each patient, using OCL 503 as the embolic agent. Patients in Cohort 1 will proceed to hysterectomy 1 week after embolization, and patients in Cohort 2 will undergo hysterectomy 1 month after embolization. Tumor response, as measured by changes in leiomyomata size and perfusion, will be determined by Magnetic Resonance Imaging or Magnetic Resonance Angiography. Histology of the resected uterus will be conducted to evaluate inflammatory response and viable tumour tissue.

Official Title
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An Open Label, Single Center, Pilot Study to Evaluate the Safety and Effectiveness of OCL 503 in the Treatment of Women With Leiomyomata Scheduled for Hysterectomy

Conditions
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Leiomyomata

Intervention / Treatment
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* Device: OCL 503 (uterine artery embolization)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: presence of one or more of the following symptoms: abnormal menstrual bleeding, prolonged menstrual period, pelvic pain, or bulk-related symptoms that are attributed to uterine fibroids (bulk-related symptoms include pelvic pressure, abdominal distension, abdominal bloating, constipation, backache, urinary frequency, urinary retention, ureteral dilation, and rectal pressure), and the intensity of uterine fibroid-related symptoms, which are sufficiently sever to warrant hysterectomy, and the patient's medical history, physical examination, and the results of imaging by ultrasound or MRI; are between the ages of 30 and 55 years, inclusive; have had a pelvic examination by a gynaecologist within the previous 6 months; have had a normal Pap smear within the last 12 months; have had an endometrial biopsy within the previous three to six months, as appropriate to patient history; are premenopausal with menstrual cycles lasting between 22 and 35 days. A follicle stimulating hormone (FSH) value obtained within three months prior to the procedure must be < 40 IU/L; are scheduled for total abdominal hysterectomy; are willing and able to provide written, informed consent. Exclusion Criteria: have been treated with gonadotropin-releasing hormone (GnRH) agonists within the previous 12 weeks; have a American Society of Anesthesiologists (ASA) score ≥ 3; have abnormally large ovarian arteries, as assessed by MRA and determined by the Investigator; have an undiagnosed pelvic mass outside the uterus; have claustrophobia or other contraindications to the performance of the pre- and post-procedure MRI studies including the presence of metal implants, metal plates, bone pins, bone screws, neurostimulators, cardiac pacemakers, aneurysm clips, cochlear or retinal implants, permanent hearing aids, or permanent eye-liner; have pedunculated subserosal fibroids with an attachment to the uterus less than one third of the greatest diameter of the fibroid; who do not agree to use contraceptives from Visit 1 until undergoing total abdominal hysterectomy; have compromised hematopoietic function; have hepatic dysfunction defined as liver function tests 30% above the upper limit of normal; have an active gynecologic or systemic infection; have renal dysfunction as defined by a serum creatinine > 1.5 mg/dL have a history of gynecologic malignancy; have had a documented anaphylactic reaction to a drug or anesthetic, or an allergic reaction to iodine contrast media not controlled by antihistamines or steroids; have received other investigational drugs or who have had experimental therapy within the past four weeks or are participating in any other concurrent experimental therapy; have a uterine volume < 250 mL or approximately > 24 weeks gestation; have known endometrial hyperplasia, adenomyosis, or pelvic inflammatory disease; have abnormal coagulation profiles; are allergic to bovine collagen;

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 - Uterine Artery Embolization<br>Women treated with OCL 503 proceeding to hysterectomy 1 week post embolization. OCL 503 will be administered by catheter to the uterine artery(ies) to achieve blood flow stasis. | Device: OCL 503 (uterine artery embolization)<br>* Transcatheter embolization of the uterine artery(ies) using an embolic agent.<br>|
| Experimental: Cohort 2 - Uterine Artery Embolization<br>Women treated with OCL 503 proceeding to hysterectomy 1 month post embolization. OCL 503 will be administered by catheter to the uterine artery(ies) to achieve blood flow stasis. | Device: OCL 503 (uterine artery embolization)<br>* Transcatheter embolization of the uterine artery(ies) using an embolic agent.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious Adverse Events | Short-term safety of OCL 503 at 7 days post treatment of women with leiomyomata by UAE, as measured by Adverse Events reporting - Serious Adverse Events | 7 days | 
| Change in Fibroid Perfusion From Baseline at 7 Days Post Treatment | Number of participants with decreased fibroid perfusion from baseline at 7 days post treatment of women with leiomyomata by UAE - Decreased Fibroid Perfusion Fibroid perfusion indicative of blood flowing to the fibroid at baseline and 7 days after embolization was determined using MRI. | Baseline and 7 days | 
| Number of Participants With Serious Adverse Events | Short-term safety of OCL 503 at 28 days post treatment of women with leiomyomata by UAE, as measured by Adverse Events reporting - Serious Adverse Events | 28 days | 
| Change in Fibroid Perfusion From Baseline at 28 Days Post Treatment of Women With Leiomyomata by UAE | Number of participants with decreased fibroid perfusion from baseline at 28 days post treatment of women with leiomyomata by UAE. | Baseline and 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tissue Necrosis Assessed by Histology Graded Scale at 7 Days Post Treatment of Women With Leiomyomata by UAE | Tissue necrosis assessed by histology at 7 days post treatment of women with leiomyomata by UAE - Fibroid necrosis observed | 7 days | 
| Inflammatory Response Assessed by Histology at 7 Days Post Treatment of Women With Leiomyomata by UAE | Inflammatory response assessed by histology at 7 days post treatment of women with leiomyomata by UAE - Perivascular inflammation - Low Grade | 7 days | 
| Tissue Necrosis Assessed by Histology Graded Scale at 28 Days Post Treatment of Women With Leiomyomata by UAE | Tissue necrosis assessed by histology graded scale at 28 days post treatment of women with leiomyomata by UAE - Fibroid Necrosis | 28 days | 
| Inflammatory Response Assessed by Histology at 28 Days Post Treatment of Women With Leiomyomata by UAE | Inflammatory response assessed by histology at 28 days post treatment of women with leiomyomata by UAE - Perivascular Low Grade | 28 days |