@article{79b1a82f2829433e9b01cd3da89b4b1d,
title = "A Phase I Clinical Trial to Assess Safety and Tolerability of Injectable Collagenase in Women with Symptomatic Uterine Fibroids",
abstract = "Uterine fibroids feature excessive deposition of types I and III collagen. Previous ex vivo studies showed an FDA-approved collagenase (EN3835)-digested types I and III collagen fibers in fibroid tissues; however, collagenase had not been evaluated in vivo for effects on uterine fibroids. The objective was to assess the safety and tolerability of collagenase injection directly into uterine fibroids. This was a prospective, open label, dose escalation study. The study participants were fifteen women aged 35–50 years with symptomatic uterine fibroids planning to undergo hysterectomy. Three subjects received saline and methylene blue, three subjects received a fixed dose of EN3835, and 9 subjects received stepped, increasing dosages of EN3835, all by transvaginal, ultrasound-guided injections. Primary outcome measures were safety and tolerability of the injection and change in collagen content between treated and control tissues. There were no significant adverse events following injection of EN3835 into uterine fibroids. Masson{\textquoteright}s trichrome stains revealed a 39% reduction in collagen content in treated samples compared to controls (p <0.05). Second harmonic generation (SHG) analysis showed treated samples to have a 21% reduction in density of collagen compared to controls. Picrosirius-stained collagenase-treated fibroids showed collagen fibers to be shorter and less dense compared to controls. Subjects reported a decrease in fibroid-related pain on the McGill Pain Questionnaire after study drug injection in Group 2 at both 4–8 days and 60–90 days post-injection. The findings indicated that injection of collagenase was safe and well tolerated. These results support further clinical investigation of collagenase as a minimally invasive treatment of uterine fibroids. NCT0289848.",
keywords = "Clostridium histolyticum, Collagenase, Leiomyoma, Phase 1 study, Uterine fibroids",
author = "Bhuchitra Singh and Holly Sims and Irene Trueheart and Khara Simpson and Wang, {Karen C.} and Kristin Patzkowsky and Thomas Wegman and Soma, {Jean Marie} and Rosina Dixon and Friederike Jayes and Kristin Voegltine and Gayane Yenokyan and Su, {Szu Chi} and Phyllis Leppert and Segars, {James H.}",
note = "Funding Information: We wish to express gratitude for contributions of Ms. Charlesa Plummer and Ms. Maybel Wahab, the Johns Hopkins Community Physicians (JHCP) Gynecologists Drs. Stephen Martin, Tamara DeShawn Terry, and Meghan Pratts O'Connor and the Johns Hopkins Investigational Drug Service, particularly Ms. Andi Weiss. This publication was also made possible by the Johns Hopkins Institute for Clinical and Translational Research (ICTR), which is funded in part by Grant Number UL1 TR001079 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS, or NIH. JHS was supported, in part, by the Howard and Georgeanna Jones Foundation. The clinical trial was registered with clinicaltrials.gov (NCT02889848). Funding Information: Dr. Rosina Dixon and Jean-Marie Soma are employed by BioSpecifics Technologies Corporation. The late Dr. Thomas Wegman was President of BioSpecifics Technologies Corporation. The study was funded by Advance Biofactures Corporation, Lynbrook, NY, a subsidiary of Biospecifics Technologies Corporation. Biospecifics staff participated in study design, secured the IND, and monitored study progress in keeping with industry standards, and manuscript preparation, but did not participate in subject recruitment, data collection, data analysis, and preparation of figures and tables or influence the presentation or interpretation of results, in keeping with the principles of the Messenden Code of Ethics and Accountability. J.H.S. is active on the following boards: The American Board of Obstetrics and Gynecology, the Society for Reproductive Investigation and the American Gynecological and Obstetrical Society. Dr. Segars has received sponsored research funding for clinical trials involving from Biospecifics, Bayer, and Abbvie and served as a consultant for Myovant. The other author(s) report(s) no conflicts of interest. Funding Information: We wish to express gratitude for contributions of Ms. Charlesa Plummer and Ms. Maybel Wahab, the Johns Hopkins Community Physicians (JHCP) Gynecologists Drs. Stephen Martin, Tamara DeShawn Terry, and Meghan Pratts O'Connor and the Johns Hopkins Investigational Drug Service, particularly Ms. Andi Weiss. This publication was also made possible by the Johns Hopkins Institute for Clinical and Translational Research (ICTR), which is funded in part by Grant Number UL1 TR001079 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS, or NIH. JHS was supported, in part, by the Howard and Georgeanna Jones Foundation. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = sep,
doi = "10.1007/s43032-021-00573-8",
language = "English (US)",
volume = "28",
pages = "2699--2709",
journal = "Reproductive Sciences",
issn = "1933-7191",
publisher = "SAGE Publications Inc.",
number = "9",
}