A randomized interventional study designed to evaluate the safety and effectiveness of treatment with nipocalimab compared with intravenous immunoglobulinIntravenous immunoglobulin A treatment given to pregnant women with a history of FNAIT or known alloantibodies. IVIG reduces the immune reaction against fetal platelets. (IVIGIntravenous immunoglobulin A treatment given to pregnant women with a history of FNAIT or known alloantibodies. IVIG reduces the immune reaction against fetal platelets.) in pregnancies at risk for fetal and neonatal alloimmune thrombocytopenia (FNAITFetal and neonatal alloimmune thrombocytopenia A rare condition in which a mother’s immune system attacks fetal platelets, leading to dangerously low platelet levels before and/or after birth.) will be recruiting patients in the near future.
A description of the protocol of the FREESIA-3 trial, which is being sponsored by Janssen Research & Development, was recently posted on the National Library of Medicine’s website.
The rare disorder FNAIT occurs when the immune system of a pregnant patient attacks the fetus’s platelets. This, in turn, can lead to an elevated risk for internal bleedingFetal hemorrhage Any bleeding that occurs before birth. In FNAIT, this usually results from extremely low platelet counts., which can be life-threatening in the fetus and/or newborn.
Currently, the investigational monoclonal antibody nipocalimab, which has been designed to bind with high affinity to block the fragment crystallizable (Fc) neonatal receptor (FcRnFc receptor A specialized transport protein. In FNAIT, it carries maternal antiplatelet IgG antibodies across the placenta into the fetus, which destroys the fetus's platelets.) inhibitor and thus decrease levels of immunoglobulin G (IgG) antibodies, is the only therapy in clinical development for the treatment of FNAIT.
Read more about FNAIT testing and diagnosis
In the phase 3 FREESIA-3 trial, the investigators are seeking to evaluate the safety and effectiveness of nipocalimab compared with IVIG for reducing the risk for severe FNAIT in at-risk pregnant patients.
Inclusion criteria for enrollment in the FREESIA-3 study comprise the following:
- Pregnant woman in whom the gestational age (GA) of the fetus is between 13 and 16 weeks at their initial visit
- History of one or more previous pregnancies affected by FNAIT, in which standard-risk FNAIT (low neonatal platelet counts, along with no occurrence of intracranial hemorrhageBrain bleed Bleeding inside the fetal brain, also known as an intracranial hemorrhage. In FNAIT, it's often caused by severe thrombocytopenia and can lead to long-term disability or death. [ICH] or severe fetal/neonatal hemorrhageFetal hemorrhage Any bleeding that occurs before birth. In FNAIT, this usually results from extremely low platelet counts.), or high-risk FNAIT (fetus/neonate with ICH or severe hemorrhage) was reported
- Current pregnancy exhibits presence of maternal anti–human platelet antigenHuman platelet antigen Proteins found on the surface of platelets. Incompatibility between maternal and fetal human platelet antigens can trigger FNAIT. (HPAHuman platelet antigen Proteins found on the surface of platelets. Incompatibility between maternal and fetal human platelet antigens can trigger FNAIT.)-1a and/or anti-HPA-5b alloantibodyAlloantibody An antibody a pregnant woman develops in response to fetal platelets that carry a different human platelet antigen. These antibodies can cross the placenta and destroy fetal platelets., as well as positive fetal HPA-1a and/or anti-HPA-5b genotype, per verification in maternal blood via cell-free DNA
- Health status of pregnant patient deemed stable based on results of medical history, physical exam, vital signs, electrocardiogram, and laboratory tests conducted at screening
- Willingness to relinquish participating in another clinical trial of an investigational therapy until the final follow-up visit of this study
Exclusion criteria included multiple gestation (twins or more); severe eclampsia in a prior pregnancy; history of stroke, myocardial infarction, or unstable ischemic heart disease; known allergies, intolerance, or hypersensitivity to nivocalimab or IVIG; and confirmed or suspected clinical immunodeficiency syndrome or family history of congenital or hereditary immunodeficiency.
Pregnant patients between 13 and 16 weeks’ GA who exhibit alloantibodies against HPA-1a and/or HPA-5b will be randomized to nipocalimab or to IVIG.
The primary outcome measure is defined as “fetus/neonate death or . . . severe bleeding up to the first week post birth or platelet countPlatelet count A measure of how many platelets are in the blood. FNAIT is characterized by severely reduced counts in a fetus or newborn. of <30 x 109/L,” which is the criteria for diagnosing thrombocytopeniaThrombocytopenia A platelet count that is lower than normal..
Secondary study outcomes included the following:
- Platelet count of neonate at birth
- Fetus/neonate with outcome of death
- Neonate with platelet counts of <10 x 109/L, <30 x 109/L, <50 x 109/L, or <150 x 109/L at birth
- Nadir (lowest) platelet count of neonate
- Platelet transfusionPlatelet transfusion A treatment for newborns with very low platelet counts that ideally uses HPA-compatible or washed maternal platelets. required in neonate
- Number of donor exposures for platelet transfusions
- Adjudicated (resolved) bleeding in neonate/fetus
- Postnatal IVIG needed to treat thrombocytopenia in neonate
- Neonate/infant in whom an infection is reported, which is deemed a treatment-emergent adverse event
