An investigational drug that may block harmful antibodies from passing through the placenta of an expectant mother to the fetus is the focus of a new clinical trial led by Kenneth Moise, MD, a maternal-fetal medicine specialist at The University of Texas Health Science Center at Houston (UTHealth).
McGovern Medical School at UTHealth is the first site in the U.S. to participate in this global clinical trial, which is focused on evaluating the safety and efficacy of the investigational drug M281 by Momenta Pharmaceuticals. Researchers will study whether the drug could eliminate the need for intrauterine transfusions (IUT) through the umbilical cord to fetuses who are at high risk for developing hemolytic disease of the fetus and newborn (HDFN), a rare and potentially life-threatening condition.
HDFN is a blood disorder in a fetus or newborn that occurs when an Rh incompatibility exists between the blood types of a mother and baby. The mother’s immune system can consider a baby’s red blood cells as foreign and develop antibodies that attack the proteins on the fetal red blood cells. This attack can lead to fetal anemia, which can be fatal. In general, HDFN affects between 4,000 and 8,000 pregnancies each year in the U.S. alone, usually in a mother’s second pregnancy.
Moise, a principal investigator for the global Phase II trial, is a professor in the Department of Obstetrics, Gynecology, and Reproductive Sciences and Department of Pediatric Surgery and co-director of The Fetal Center at Children’s Memorial Hermann Hospital in collaboration with UT Physicians.
The standard of care for severe HDFN is for the mother and her unborn baby to undergo a series of IUTs with donated, compatible red blood cells. Currently, there are no U.S. Food and Drug Administration-approved drugs to treat women at risk of HDFN.
“I want to be among the last doctors to perform IUTs on unborn babies with blood incompatibility problems,” said Moise, who was honored with this year’s Society of Maternal Fetal Medicine’s Lifetime Achievement Award for more than three decades of work on HDFN and its most common form, Rh disease. “It’s time we stop putting moms through the stress of the procedure. Many complications, like infection, can arise anytime a needle is placed into a baby’s umbilical cord in the womb. In this study population of women with very severe HDFN, IUTs carry up to a 20 percent risk of fetal death, depending on stage of the pregnancy and experience of the center or clinic.”
M281 is an investigational monoclonal antibody engineered to block the neonatal Fc receptor (FcRn), a protein in the placenta that helps transport immunoglobulin G (IgG) antibodies from the mother to the fetus. The study drug is administered through a weekly intravenous infusion.
“The study drug was designed to inhibit the potentially harmful antibodies from passing through the placenta from early to late pregnancy, while also decreasing the amount of circulating antibodies in the mother,” Moise said. “This provides a two-pronged approach to lowering the amount of potentially dangerous antibodies from reaching the fetus. If successful, it will allow maternal-fetal specialists to replace a risky surgical treatment with a medical treatment that carries much less risk. This would enable women who thought they couldn’t have any more babies to consider growing their family. I am looking forward to investigating the capabilities of this investigational drug for women at risk of HDFN.”
Results from studies of placentas obtained from volunteers at the time of their delivery, recently published in the American Journal of Obstetrics & Gynecology, showed M281 significantly reduced the placental transfer of IgG, while only small amounts of the drug entered the fetal circulation.
The effectiveness of the drug will be measured by looking at the percentage of participants with a live birth at or after 32 weeks of pregnancy without the need for an IUT. The study is enrolling 15 patients at multiple international sites.
Key eligibility criteria for participation in the clinical trial include being over the age of 18 with an estimated gestational age of eight to 13 weeks at enrollment, and having had a previous pregnancy that included one of the following conditions: severe fetal anemia, fetal hydrops, or stillbirth with fetal or placental pathology indicative of HDFN due to anti-D or anti-Kell antibodies. Enrolled patients will have their evaluations and ultrasounds at The Fetal Center, and will receive their infusions of M281 as an outpatient at the UTHealth Clinical Research Unit at Memorial Hermann-Texas Medical Center.
If you are pregnant and would like more details, visit ClinicalTrials.gov or call 832-325-7288.