Fibroids, UterinePhase 1NCT02889848
Safety and Tolerability of Collagenase Clostridium Histolyticum (EN3835) to Treat Uterine Leiomyoma (Fibroids)
A Phase 1 study testing Saline and EN3835 in people with Fibroids, Uterine and Leiomyoma, run by Advance Biofactures Corporation at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 50 years, women only
- Conditions the study is for
- Fibroids, Uterine, Leiomyoma
- What is being tested?
- Saline and EN3835
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Oct 2016to 15 Nov 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open Label, Dose Escalation Study to Assess Safety and Tolerability of Collagenase Clostridium Histolyticum (EN3835) in Subjects With Uterine Leiomyoma (Fibroids)
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.
Read the detailed description
Collagenase enzyme breaks down collagen and has shown efficacy in clinical trials for a number of diseases for which there is an accumulation of collagen.
It is possible that lysis of collagen may reduce the collagen content of fibroids thus decreasing the size of fibroids, and possibly reducing the stiffness of fibroids. This may result in reducing the symptoms of pain and bleeding associated with fibroids.
In this study three subjects will be injected with saline only followed immediately by hysterectomy in order to evaluate the safety and effectiveness of the injection method.
Twelve subjects will receive a single injection of study drug as follows: three subjects will receive a set dose of collagenase enzyme followed by hysterectomy or myomectomy 24-96 hours later (Group 1) to evaluate safety of the injection of study drug. Nine subjects will then receive increasing doses of collagenase enzyme followed by hysterectomy or myomectomy 60-90 days later (Group 2).
- Conditions
- Fibroids, Uterine, Leiomyoma
- Being tested
- Saline, EN3835
- Medical subject headings
- Leiomyoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalineOther
Saline injection
EN3835Drug
Also called Collagenase clostridium histolyticum
Comparison of maximum marketed dose and multiple doses EN3835
| Study group | Role | What they receive |
|---|---|---|
| Saline only | Sham comparator | Injection of saline to assess the injection procedure Receives: Other: Saline |
| 1.16 mg EN3835 | Experimental | Injection of maximum marketed dose of EN3835 regardless of fibroid size Receives: Drug: EN3835 |
| Dose 1 | Experimental | Injection of 0.05 mg EN3835 per cm3 fibroid Receives: Drug: EN3835 |
| Dose 2 | Experimental | Injection of 0.1 mg EN3835 per cm3 fibroid Receives: Drug: EN3835 |
| Dose 3 | Experimental | Injection of 0.2 mg EN3835 per cm3 fibroid Receives: Drug: EN3835 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Through hysterectomy or myomectomy (average = 60-90 days post injection)
Secondary outcomes (5)
Change in symptoms of pain and bleeding and quality of life
Determined by standardized questionnaires for menstrual distress, quality of life and sexual activity; McGill Pain Questionnaire
Measured: Throughout the study prior to hysterectomy or myomectomy(avg 60-90 days post injection study drug)
Reduction in size of treated fibroids- Group 2
Size of fibroid to be determined post hysterectomy or myomectomy
Measured: 60-90 days post injection study drug
Increased rate of apoptosis of treated fibroids -Group 2
Specimens to be taken post hysterectomy or myomectomy and evaluated by TUNEL staining
Measured: 60-90 days post injection study drug
Reduction in collagen content of treated fibroids-Group 2
Specimens to be taken post hysterectomy or myomectomy and by tested histology stains
Measured: 60-90 days post injection study drug
Reduction in stiffness of treated fibroid-Group 2
Specimens to be taken post hysterectomy or myomectomy and tested via rheometry
Measured: 60-90 days post injection study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2016 (estimated)
- Study start27 Oct 2016
- Primary completion5 Oct 2018
- Study completion15 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fibroids, UterineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advance Biofactures Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James Segars, M.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02889848
- Sponsor's protocol ID
- FIB1154
- Status last verified
- Jun 2018
- First submitted
- 22 Aug 2016
- Last updated
- 10 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 34323413
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Dose Escalation Study to Assess Safety and Tolerability of Collagenase Clostridium Histolyticum (EN3835) in Subjects With Uterine Leiomyoma (Fibroids)
- ClinicalTrials.gov ID
- NCT02889848
- Acronym / sponsor ID
- FIB1154
- Conditions
- Fibroids, Uterine, Leiomyoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Advance Biofactures CorporationIndustry (pharma, biotech, devices)
- Study start
- 27 Oct 2016 (actual)
- Primary completion
- 5 Oct 2018 (actual)
- Study completion
- 15 Nov 2018 (actual)
- First posted
- 7 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Collagenase enzyme breaks down collagen and has shown efficacy in clinical trials for a number of diseases for which there is an accumulation of collagen.
It is possible that lysis of collagen may reduce the collagen content of fibroids thus decreasing the size of fibroids, and possibly reducing the stiffness of fibroids. This may result in reducing the symptoms of pain and bleeding associated with fibroids.
In this study three subjects will be injected with saline only followed immediately by hysterectomy in order to evaluate the safety and effectiveness of the injection method.
Twelve subjects will receive a single injection of study drug as follows: three subjects will receive a set dose of collagenase enzyme followed by hysterectomy or myomectomy 24-96 hours later (Group 1) to evaluate safety of the injection of study drug. Nine subjects will then receive increasing doses of collagenase enzyme followed by hysterectomy or myomectomy 60-90 days later (Group 2).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Saline only | Sham comparator | Other: SalineInjection of saline to assess the injection procedure |
| 1.16 mg EN3835 | Experimental | Drug: EN3835Injection of maximum marketed dose of EN3835 regardless of fibroid size |
| Dose 1 | Experimental | Drug: EN3835Injection of 0.05 mg EN3835 per cm3 fibroid |
| Dose 2 | Experimental | Drug: EN3835Injection of 0.1 mg EN3835 per cm3 fibroid |
| Dose 3 | Experimental | Drug: EN3835Injection of 0.2 mg EN3835 per cm3 fibroid |
Who may qualify
- Ages
- 35 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SalineSaline injection | Other | Saline only |
| EN3835Also: Collagenase clostridium histolyticumComparison of maximum marketed dose and multiple doses EN3835 | Drug | 1.16 mg EN3835, Dose 1, Dose 2, Dose 3 |
Primary outcome
Number of participants with treatment-related adverse events following a single injection of EN3835 into a fibroid
Time frame: Through hysterectomy or myomectomy (average = 60-90 days post injection)
Assessed by number of subjects with uterine injury or peritoneal irritation determined post hysterectomy
5 secondary outcomes
Change in symptoms of pain and bleeding and quality of life
Time frame: Throughout the study prior to hysterectomy or myomectomy(avg 60-90 days post injection study drug)
Reduction in size of treated fibroids- Group 2
Time frame: 60-90 days post injection study drug
Increased rate of apoptosis of treated fibroids -Group 2
Time frame: 60-90 days post injection study drug
Reduction in collagen content of treated fibroids-Group 2
Time frame: 60-90 days post injection study drug
Reduction in stiffness of treated fibroid-Group 2
Time frame: 60-90 days post injection study drug
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2019.
- Derived from this study: PubMed 34323413Islam 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Segars, M.D. principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Saline and EN3835 in people with Fibroids, Uterine and Leiomyoma, run by Advance Biofactures Corporation at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events following a single injection of EN3835 into a fibroid (time frame: Through hysterectomy or myomectomy (average = 60-90 days post injection)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02889848, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2019; AzTrials last refreshed its copy on 8 Nov 2026.