A Novel Device for Cervical Insufficiency in Pregnant Women

Abstract Cervical insufficiency is a severe complication of pregnancy that leads to preterm birth. Preterm birth is a significant cause of morbidity and mortality in newborns infants and can cause long-term disabilities during childhood. Healthcare spending for preterm infants is expensive, with infants born before 37 weeks costing an average of $76,000 in the first six months after birth. Cervical insufficiency is caused by structural failure of the cervix. In normal pregnancy, the cervix is strong enough to stay closed throughout pregnancy. However, in cases of cervical insufficiency, the cervix is unable to retain the pregnancy during fetal growth. The cervix dilates in the absence of uterine contractions, which leads to preterm birth. The mainstay of treatment is cervical cerclage, a surgical procedure that uses a suture to compress the cervix. Cervical compression prevents preterm dilation and maintains a sterile barrier between the fetal and vaginal environments. Approximately 15,000 cerclage surgeries are performed each year in the U.S. (0.4% of pregnancies). Although cerclage is well-integrated into clinical practice, the efficacy of cerclage is limited, and adverse effects occur. Cx Therapeutics is developing the Cx Device, a medical device to improve the efficacy of cerclage and to decrease its adverse effects. The Cx Device is composed of four silicone plates arranged circumferentially around the cervix. A suture is threaded through each plate and alternately passes into the cervix for placement. Upon tightening, the suture compresses the plates, which in turn compress the tissue, effectively applying compression more evenly to the cervix. More uniform application of compression decreases stress concentrations in the tissue. Previous work has demonstrated the Cx Device has a higher load carrying capability compared to cerclage. The Cx Device also lengthens the cervix compared to cerclage, suggesting the Cx Device will lead to improved efficacy in vivo. The current Direct to Phase II proposal will continue to advance this novel device for cervical insufficiency closer to commercialization by completing engineering validation and conducting a limited first-in-human study. Cx Therapeutics brings together a highly qualified team with expertise in medical device design, product development, regulatory affairs, and high-risk obstetrics, to achieve the following Aims. Aim 1 will finalize the design of the device and complete engineering verification. Engineering activities will be informed by computational modeling and usability testing with physicians. Experiments in Aim 2 will validate the Cx Device through compression measurements on ex vivo human tissue and assess its usability in the operating room. Experiments in Aim 3 will assess biocompatibility by performing studies to determine in vitro cytotoxicity and evaluate long-term effects in a pig model of pregnancy. At the end of Phase II, Cx Therapeutics will have developed a production equivalent device that satisfies both engineering and clinical requirements. The activities of Phase II will position Cx Therapeutics for a Phase IIB designed to secure FDA clearance and complete a clinical trial in pregnancy.