Evaluation of Nipocalimab for Reducing Severe Fetal and Neonatal Alloimmune Thrombocytopenia Risk in At-risk Pregnancies: A Double-blind, Randomized, Placebo-controlled Trial

The primary objective of this study is to evaluate the **superiority** of nipocalimab compared with placebo in reducing the risk of severe **Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)**. This is clinically relevant as FNAIT is a serious condition that can lead to significant morbidity and mortality in affected neonates, and effective prevention strategies are crucial for at-risk pregnancies.

Secondary objectives include:

• Evaluating the efficacy of nipocalimab compared with placebo on FNAIT-related thrombocytopenia.
• Assessing the efficacy of nipocalimab compared with placebo in reducing the risk of FNAIT-related bleeding.

The clinical trial involves a total of **18 participants** who are exclusively **female** and are part of a vulnerable population. The study population consists of pregnant women aged **18 years or older** with an estimated gestational age between Week 13 to 16 at the time of randomization. Participants were selected based on their medical history, specifically having at least one prior pregnancy affected by **Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)**, without any instances of fetal or neonatal intracranial hemorrhage or severe hemorrhage. The current pregnancy must show the presence of maternal anti-HPA-1a alloantibody and a positive fetal HPA-1a genotype, confirmed by cell-free fetal DNA in maternal blood. The general health status of participants is considered stable, as determined by the investigator through physical examination, medical history, vital signs, 12-lead ECG, and clinical laboratory tests conducted during screening. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the **safety** and **efficacy** of **nipocalimab** in reducing the risk of **Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)** in at-risk pregnancies. This study is a **randomized**, **double-blind**, **placebo-controlled** trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thereby minimizing bias. The trial is expected to commence on February 1, 2024, and conclude by December 5, 2029, with a maximum treatment period of 28 days for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, pregnancy status, and medical history. The main inclusion criteria include being 18 years or older, pregnant with an estimated gestational age between weeks 13 to 16, and having a history of at least one prior pregnancy affected by FNAIT. The screening will involve physical examinations, medical history reviews, and laboratory tests. Following randomization, participants will receive either **nipocalimab** or a placebo via **intravenous use**. Subsequent follow-up visits will monitor the participants' health status, assess any adverse events, and evaluate the primary endpoint, which includes the adverse outcome of death or severe bleeding in utero up to the first week post-birth, or a platelet count at birth of less than 30×10⁹/L in a fetus/neonate.

The end-of-study visit will occur after the treatment period, where final assessments will be conducted to gather data on the secondary endpoints, such as platelet count at birth and adjudicated bleeding events. Participant involvement is expected to last for the duration of the treatment period plus any additional time required for follow-up assessments. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or any situation where continued participation is deemed unsafe by the investigator. The trial aims to provide robust data on the potential benefits of **nipocalimab** in managing FNAIT, contributing to improved maternal and neonatal health outcomes.

The clinical trial involves the administration of **nipocalimab**, an investigational medication, to evaluate its efficacy in reducing the risk of Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) in at-risk pregnancies. **Nipocalimab** is provided in two pharmaceutical forms: a **solution for injection** and a **solution for infusion**. Both forms are intended for **intravenous use**. The solution for injection is identified by the product code JNJ-80202135 and is manufactured by Janssen-Cilag International N.V. The active substance, **nipocalimab**, is a protein-based monoclonal antibody targeting the neonatal Fc receptor. The dosing schedule is designed to ensure a maximum treatment period of 28 days, with specific dosing units and amounts not explicitly defined in the trial data.

In addition to the experimental treatment, a **placebo** is utilized in the study to serve as a comparator. The placebo is a **saline, 0.9% sodium chloride solution for injection**, which does not contain any active pharmaceutical ingredients. The placebo is administered in a manner consistent with the experimental treatment to maintain the double-blind nature of the trial. The use of a placebo allows for the assessment of the true efficacy and safety profile of **nipocalimab** by providing a baseline for comparison.

The efficacy of **nipocalimab** in reducing the risk of Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) will be assessed in a double-blind, randomized, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is 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 30×10⁹/L in a fetus or neonate. Secondary endpoints include the platelet count at birth in a neonate and adjudicated bleeding in utero up to the first week post-birth in a fetus or neonate.

The trial is designed to compare the efficacy of **nipocalimab** with a placebo in pregnant participants who are at risk. The study will involve the administration of **nipocalimab** as a solution for injection or infusion, with a maximum treatment period of 28 days. The efficacy parameters will be collected and analyzed at specified time points, including at birth and during the first week post-birth, using validated clinical assessments and laboratory tests. The trial aims to provide robust data on the potential of **nipocalimab** to mitigate severe outcomes associated with FNAIT in at-risk pregnancies.