Randomized, Open-Label Study of Nipocalimab Versus Human Normal Immunoglobulin (IV) in Pregnancies at Risk for Fetal and Neonatal Alloimmune Thrombocytopenia

The primary objective of this multicenter, open-label, randomized study is to assess the **efficacy** of the study intervention, either **nipocalimab** or **intravenous immunoglobulin (IVIG)**, in reducing the risk of severe **Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)**. This condition is clinically significant as it can lead to severe bleeding complications in the fetus and neonate, potentially resulting in morbidity or mortality. The study aims to provide insights into effective treatment options for pregnancies at risk of FNAIT, thereby improving maternal and fetal outcomes.

The clinical trial involves a total of **36 participants** who are exclusively **female** and aged **18 years or older**. The study population is specifically composed of pregnant women with an estimated gestational age between Week 13 to 16 at the first visit, although screening may commence as early as gestational age Week 8. Participants are required to have a current pregnancy with the presence of maternal anti-HPA-1a and/or anti-HPA-5b alloantibody, and a positive fetal HPA-1a and/or anti-HPA-5b genotype, as confirmed by cell-free fetal DNA in maternal blood. The health status of participants is considered stable based on a comprehensive assessment including physical examination, medical history, vital signs, 12-lead ECG, and clinical laboratory tests conducted during screening. The trial focuses on individuals with **Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)**, and the selection process ensures that the participants meet these specific criteria to assess the efficacy of the study intervention on the risk of severe FNAIT. The trial does not include male subjects, and the population is considered vulnerable due to the nature of the condition and the pregnancy status of the participants.

The clinical trial is designed as a **randomized**, open-label study to evaluate the efficacy of **nipocalimab** or **intravenous immunoglobulin (IVIG)** in pregnancies at risk of **Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)**. The trial aims to assess the impact of the study interventions on the risk of severe FNAIT. Participants will be randomly assigned to receive either nipocalimab or IVIG, with the primary endpoint being the adverse outcome of death or adjudicated severe bleeding in utero, up to the first week post-birth, or a platelet count at birth of less than 30×10^9/L in a fetus/neonate.

The trial is expected to commence recruitment on January 1, 2025, and is estimated to conclude by December 5, 2029. The study will involve multiple visits, starting with a screening visit to confirm eligibility based on criteria such as age, gestational age, and the presence of specific alloantibodies. The inclusion visit will occur between gestational weeks 13 to 16, with screening potentially starting as early as week 8. Follow-up visits will be scheduled throughout the pregnancy to monitor the health status of the participants and the efficacy of the treatment. The end-of-study visit will occur after the birth of the child to assess the primary and any secondary endpoints.

Participant involvement is expected to last for the duration of the pregnancy, with the maximum treatment period for nipocalimab being 29 weeks and for IVIG being 30 weeks. Conditions that may lead to early termination from the study include significant adverse events or any changes in the participant's health status that, in the investigator's opinion, would warrant discontinuation of the study intervention. The trial is not categorized as low intervention and is classified as a Phase 3 study, focusing on the efficacy and safety of nipocalimab in the specified patient population.

The clinical trial involves the administration of **Nipocalimab**, an investigational drug, under the product name JNJ-80202135. Nipocalimab is a **protein**-based therapeutic agent classified as a human monoclonal antibody targeting the neonatal Fc receptor. It is provided in the form of a **solution for injection** and is administered via **intravenous use**. The maximum treatment period for Nipocalimab is 29 days. The dosing schedule and specific dosage amounts are not specified in the available data, and participant compliance will be monitored according to the study protocol.

In addition to the experimental treatment, the study includes a comparator treatment using **Human Normal Immunoglobulin (IV)**, also known as IVIG. This comparator is a **blood-derived** product used for its immunomodulatory properties. It is administered as a **solution for injection** through **intravenous use**. The maximum treatment period for IVIG is 30 days. As with Nipocalimab, the specific dosing schedule and dosage amounts are not detailed in the provided information, and adherence to the treatment regimen will be monitored throughout the study.

Furthermore, the trial incorporates the use of **Prednisone**, a **chemical** substance, as part of the treatment regimen. Prednisone is administered in **tablet** form and taken **orally**. The maximum treatment period for Prednisone is 22 days. The data does not specify the exact dosage or frequency of administration, and participant compliance will be assessed as per the study's compliance monitoring procedures.

The efficacy of the clinical trial will be assessed by evaluating the primary endpoint, which is the adverse outcome of death or adjudicated severe bleeding in utero, and up to the first week post-birth, or a platelet count at birth of less than 30×10⁹/L in a fetus/neonate. This endpoint is critical in determining the effectiveness of the study intervention in reducing the risk of severe **Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)**. The trial is designed as a multicenter, open-label, randomized study comparing the efficacy of Nipocalimab or IVIG in pregnancies at risk of FNAIT.