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

NCT02889848 | Completed Phase 1

• 1 other identifier: FIB1154
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot study evaluates the safety and tolerability of a single injection of collagenase enzyme directly into a uterine fibroid in subjects already selected for hysterectomy or myomectomy. Fibroids contain excessive amounts of collagen and it is possible that digestion of collagen may be beneficial in reducing pain and bleeding associated with fibroids. Three subjects will be injected with saline only to evaluate the safety and effectiveness of the injection method. Additional subjects will then be injected with increasing doses of study drug.

Conditions

Fibroids, Uterine; Leiomyoma

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events following a single injection of EN3835 into a fibroid

  Assessed by number of subjects with uterine injury or peritoneal irritation determined post hysterectomy

  Through hysterectomy or myomectomy (average = 60-90 days post injection)

Secondary Outcomes (5)

• Change in symptoms of pain and bleeding and quality of life

  Throughout the study prior to hysterectomy or myomectomy(avg 60-90 days post injection study drug)

• Reduction in size of treated fibroids- Group 2

  60-90 days post injection study drug

• Increased rate of apoptosis of treated fibroids -Group 2

  60-90 days post injection study drug

• Reduction in collagen content of treated fibroids-Group 2

  60-90 days post injection study drug

• Reduction in stiffness of treated fibroid-Group 2

  60-90 days post injection study drug

Study Arms (5)

Saline only

SHAM COMPARATOR

Injection of saline to assess the injection procedure

Other: Saline

1.16 mg EN3835

EXPERIMENTAL

Injection of maximum marketed dose of EN3835 regardless of fibroid size

Drug: EN3835

Dose 1

EXPERIMENTAL

Injection of 0.05 mg EN3835 per cm3 fibroid

Drug: EN3835

Dose 2

EXPERIMENTAL

Injection of 0.1 mg EN3835 per cm3 fibroid

Drug: EN3835

Dose 3

EXPERIMENTAL

Injection of 0.2 mg EN3835 per cm3 fibroid

Drug: EN3835

Interventions

Saline OTHER

Saline injection

Saline only

EN3835 DRUG

Comparison of maximum marketed dose and multiple doses EN3835

Also known as: Collagenase clostridium histolyticum

1.16 mg EN3835; Dose 1; Dose 2; Dose 3

Eligibility Criteria

• Age: 35 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Advance Biofactures Corporation: lead

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Related Publications (1)

• Islam MS, Afrin S, Singh B, Jayes FL, Brennan JT, Borahay MA, Leppert PC, Segars JH. Extracellular matrix and Hippo signaling as therapeutic targets of antifibrotic compounds for uterine fibroids. Clin Transl Med. 2021 Jul;11(7):e475. doi: 10.1002/ctm2.475.

  PMID: 34323413 DERIVED

MeSH Terms

Conditions

Leiomyoma

Interventions

Sodium Chloride; Microbial Collagenase

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Collagenases; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases

Study Officials

• James Segars, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2016
• First Posted: September 7, 2016
• Study Start: October 27, 2016
• Primary Completion: October 5, 2018
• Study Completion: November 15, 2018
• Last Updated: July 10, 2019

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)