A Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of M281 Administered to Pregnant Women at High Risk for Early Onset Severe Hemolytic Disease of the Fetus and Newborn (HDFN)

A Multicenter, Open-label Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of M281 Administered to Pregnant Women at High Risk for Early Onset Severe Hemolytic Disease of the Fetus and Newborn (HDFN)

The purpose of this study is to evaluate the safety in mother and neonate/infant of M281 administered to pregnant women who are at high risk for Early Onset Severe Hemolytic Disease of the Fetus and Newborn (EOS-HDFN). The effectiveness of the investigational drug M281 will be measured by looking at the percentage of participants with live birth at or after gestational age (GA) 32 weeks and without a need for an intrauterine transfusion (IUT) throughout their entire pregnancy.

Study Overview

• Status: Completed
• Conditions: Hemolytic Disease of the Fetus and Newborn
• Intervention / Treatment: Drug: M281

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Expanded Access

Temporarily not available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • Sydney, Australia, 2170
    • Liverpool Hospital
• Belgium
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3N1
      • British Columbia Children's Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • CHUM - Centre hospitalier universitaire de Montreal
• Germany
  • Giessen, Germany, 35392
    • Justus-Liebig-Universität Gießen, Kinderherzzentrum
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center
• Spain
  • Granada, Spain, 18016
    • Hosp. Univ. San Cecilio
• Sweden
  • Stockholm, Sweden, SE-141 86
    • Karolinska Universitetssjukhuset Huddinge
• United Kingdom
  • Birmingham, United Kingdom, B15 2TG
    • Birmingham Children's Hospital
  • London, United Kingdom, WC1E 6DB
    • University College London Hospitals NHSFT
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center of Central Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Approximately 15 eligible participants and their offspring will be enrolled
• Each participant must meet all of the following criteria to be enrolled in the study:
• Female and greater than or equal to (>=)18 years of age
• Pregnant to an estimated gestational age of between 8 up to 14 weeks
• A previous pregnancy with a gestation that included at least one of the following prior to week 24 gestation:
• Severe fetal anemia, defined as hemoglobin less than or equal to (<=) 0.55 multiples of the median (MOM) for gestational age
• Fetal hydrops with peak systolic velocity MOM >=1.5
• Stillbirth with fetal or placental pathology indicative of hemolytic disease of the fetus and newborn (HDFN)
• Maternal alloantibody titers for anti-D of >=32, or anti-Kell titers >=4
• Free fetal deoxyribonucleic acid consistent with an antigen-positive fetus (blood sample taken from mother)
• Maternal evidence for Immunity to measles mumps, rubella, and varicella, as documented by serologies performed during Screening. If initial serologies are borderline or negative, they may be repeated at a second lab. Alternatively, vaccination records can be used to support evidence of immunity.
• Screening immunoglobulin G and albumin levels within the laboratory normal range for gestational age of pregnancy
• Willing to receive standard of care with intrauterine transfusion if clinically indicated
• Agree to receive recommended vaccinations per local standard of care for both mother and child throughout the course of the study
• It is recommended that patients are up-to-date on age-appropriate vaccinations prior to screening as per routine local medical guidelines. For study patients who received locally-approved (and including emergency use-authorized) Coronavirus Disease 2019 (COVID-19) vaccines recently prior to study entry, follow applicable local vaccine labelling, guidelines, and standard of care for pregnant women receiving immune-targeted therapy when determining an appropriate interval between vaccination and study enrollment

Exclusion Criteria:

• Currently pregnant with multiples (twins or more)
• Pre-eclampsia In current pregnancy or history of pre-eclampsia in a previous pregnancy
• Gestational hypertension in the current pregnancy
• Current unstable hypertension
• History of severe or recurrent pyelonephritis, 4 or more lower urinary tract infections in the past year or in a previous pregnancy
• History of genital herpes infection
• Active Infection at Screening or Baseline with Coxsackie, syphilis, cytomegalovirus, toxoplasmosis or herpes simplex 1 or 2, as evidenced by clinical signs and symptoms (evidence for prior Infection or exposure, but without clinical signs and symptoms of active infection is acceptable)
• Active infection with tuberculosis as evidenced by positive QuantiFERON-tuberculosis testing
• Requires treatment with corticosteroids or immunosuppression for disorders unrelated to the pregnancy (use of low-potency topical corticosteroids or intra-articular corticosteroids is permitted)
• Has received or is expected to receive any live virus or bacterial vaccine within 12 weeks prior to screening or has a known need to receive a live vaccine while receiving nipocalimab, or within 12 weeks after the last administration of nipocalimab in the study or has received Bacille Calmett-Guérin (BCG) vaccine within 1 year prior to the first administration of nipocalimab
• Currently receiving an antibody-based drug or an Fc-fusion protein drug
• Received plasmapheresis and/or intravenous immunoglobulin during the current pregnancy for treatment of HDFN
• COVID-19 infection: during the 6 weeks prior to baseline (regardless of vaccination status), have had any of: a) confirmed severe acute respiratory syndrome coronavirus(-2) (SARS-CoV-2) (COVID-19) infection (test positive), or; b) suspected SARS-CoV-2 infection (clinical features without documented test results), or; c) close contact with a person with known or suspected SARS-CoV-2 infection. Exception: may be included with a documented negative result for a validated SARSCoV-2 test: obtained at least 2 weeks after conditions a), b), c) above (timed from resolution of key clinical features if present, example fever, cough, dyspnea) and; with absence of all conditions a), b), c) above during the period between the negative test result and the baseline study visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: M281	Drug: M281; Participants will receive once weekly intravenous (IV) infusions of M281

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Maternal Participants With Treatment-emergent Adverse Events (TEAEs)	An AE was any unfavorable and unintended sign (example, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. TEAE was defined as any event occurring after the initiation of the first infusion of nipocalimab.	From baseline (Gestational Age [GA] Week 14) up to Postpartum (PP) Week 24 (up to 50 weeks)
Number of Neonates/Infants With Adverse Events (AEs)	An AE was any unfavorable and unintended sign (example, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	From Birth (PP Day 0) up to PP Week 96
Number of Maternal Participants With Treatment-emergent Serious Adverse Events (TESAEs)	SAE was defined as any untoward medical occurrence that resulted in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. An AE was any unfavorable and unintended sign (example, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. TESAEs were any SAEs occurring after the initiation of the first infusion of nipocalimab.	From baseline (Gestational Age [GA] Week 14) up to PP Week 24 (up to 50 weeks)
Number of Neonates/Infants With Serious Adverse Events (SAEs)	SAE was defined as any untoward medical occurrence that resulted in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. An AE was any unfavorable and unintended sign (example, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.	From Birth (PP Day 0) up to PP Week 96
Number of Maternal Participants With Treatment-emergent Adverse Events of Special Interest (TEAESIs)	Number of maternal participants with TEAESIs were reported. An AE was any unfavorable and unintended sign (example, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. All infections requiring anti-infective (that is, oral or intravenous antibacterial, antiviral, or antifungal) treatment and with hypoalbuminemia greater than or equal to (>=) Grade 3 (less than [<]20 gram per liter [g/L] by National Cancer Institute of Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 criteria were considered an AESI for maternal participants. TEAE was defined as any event occurring after the initiation of the first infusion of nipocalimab.	From baseline (Gestational Age [GA] Week 14) up to PP Week 24 (up to 50 weeks)
Number of Neonates/Infants With Adverse Events of Special Interest (AESIs)	Number of neonates/infants with TEAESIs were reported. An AE was any unfavorable and unintended sign (example, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. All infections requiring anti-infective (that is, oral or intravenous antibacterial, antiviral, or antifungal) treatment, unexpected/unusual childhood illnesses and Immunoglobulin G (IgG) concentrations <200 milligrams per deciliter (mg/dL) at Week 24 through Week 47 or <300 mg/dL at Week 48 through Week 96 were considered an AESI for neonates and infants.	From birth (PP Day 0) up to PP Week 96
Maternal Participants: Absolute Value of Electrocardiogram (ECG) Parameter - Mean Ventricular Rate at Baseline	Absolute value of ECG parameter - mean ventricular rate at baseline in maternal participants was reported. Electrocardiogram assessments included comments on whether the tracings were normal or abnormal, rhythm, presence of arrhythmia or conduction defects, morphology, any evidence of myocardial infarction, or ST segment, T Wave, and U Wave abnormalities.	Baseline (GA Week 14)
Maternal Participants: Absolute Value of Electrocardiogram (ECG) Parameter - Mean Ventricular Rate at GA Week 36	Absolute value of ECG parameter - mean ventricular rate at GA Week 36 in maternal participants was reported. Electrocardiogram assessments included comments on whether the tracings were normal or abnormal, rhythm, presence of arrhythmia or conduction defects, morphology, any evidence of myocardial infarction, or ST segment, T Wave, and U Wave abnormalities.	GA Week 36
Maternal Participants: Change From Baseline in ECG Parameter- Mean Ventricular Rate	Change from baseline in ECG parameter- mean ventricular rate in maternal participants was reported. Electrocardiogram assessments included comments on whether the tracings were normal or abnormal, rhythm, presence of arrhythmia or conduction defects, morphology, any evidence of myocardial infarction, or ST segment, T Wave, and U Wave abnormalities.	Baseline (GA Week 14) and GA Week 36
Number of Maternal Participants With Treatment-emergent (TE) Clinically Important Laboratory and Biomarker Immunoglobulin G (IgG) Values Over Time	Laboratory parameters included hematology, chemistry, blood Lipids panel, and Immunoglobulin G (IgG) parameters. TEAE was defined as any event occurring after the initiation of the first infusion of nipocalimab. Here, HDL: high-density lipoprotein, LDL: low-density lipoprotein. The during-pregnancy value of albumin <20 g/L was from a local laboratory and was >=20 g/L when analyzed at the central laboratory for the same time point.	From baseline (Gestational Age [GA] Week 14) up to PP Week 24 (up to 50 weeks)
Number of Neonates or Infants With Clinically Important Laboratory and Biomarker Immunoglobulin G (IgG) Values Over Time	Laboratory parameters included total bilirubin and biomarker included immunoglobulin G (IgG).	From Birth (PP Day 0) up to PP Week 96
Maternal Participants: Absolute Value of Vital Signs - Body Temperature at Baseline	Absolute value of vital signs - body temperature at baseline in maternal participants was reported.	Baseline (GA Week 14)
Maternal Participants: Absolute Value of Vital Signs - Body Temperature at GA Week 36	Absolute value of vital signs - body temperature at GA Week 36 in maternal participants was reported.	GA Week 36
Maternal Participants: Absolute Value of Vital Signs - Body Temperature at PP Week 24	Absolute value of vital signs - body temperature at PP Week 24 in maternal participants was reported.	PP Week 24
Maternal Participants: Change From Baseline in Vital Sign - Body Temperature	Change from baseline in vital signs- body temperature in maternal participants was reported.	Baseline (GA Week 14), GA Week 36, and PP Week 24
Maternal Participants: Absolute Value of Vital Signs - Respiratory Rate at Baseline	Absolute value of vital signs -respiratory rate at baseline in maternal participants was reported.	Baseline (GA Week 14)
Maternal Participants: Absolute Value of Vital Signs - Respiratory Rate at GA Week 36	Absolute value of vital signs -respiratory rate at GA Week 36 in maternal participants was reported.	GA Week 36
Maternal Participants: Absolute Value of Vital Signs - Respiratory Rate at PP Week 24	Absolute value of vital signs - respiratory rate at PP Week 24 in maternal participants was reported.	PP Week 24
Maternal Participants: Change From Baseline in Vital Sign - Respiratory Rate	Change from baseline in vital signs- respiratory rate in maternal participants was reported.	Baseline (GA Week 14), GA Week 36, and PP Week 24
Maternal Participants: Absolute Value of Vital Signs - Pulse Rate at Baseline	Absolute value of vital signs - pulse rate at baseline in maternal participants was reported.	Baseline (GA Week 14)
Maternal Participants: Absolute Value of Vital Signs - Pulse Rate at GA Week 36	Absolute value of vital signs -pulse rate at GA Week 36 in maternal participants was reported.	GA Week 36
Maternal Participants: Absolute Value of Vital Signs -Pulse Rate at PP Week 24	Absolute value of vital signs -pulse rate at PP Week 24 in maternal participants was reported.	PP Week 24
Maternal Participants: Change From Baseline in Vital Sign - Pulse Rate	Change from baseline in vital signs -pulse rate in maternal participants was reported.	Baseline (GA Week 14), GA Week 36, and PP Week 24
Maternal Participants: Absolute Value of Vital Signs - Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline	Absolute value of vital signs - SBP and DBP at baseline in maternal participants was reported.	Baseline (GA Week 14)
Maternal Participants: Absolute Value of Vital Signs - Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at GA Week 36	Absolute value of vital signs -SBP and DBP at GA Week 36 in maternal participants was reported.	GA Week 36
Maternal Participants: Absolute Value of Vital Signs - Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at PP Week 24	Absolute value of vital signs - SBP and DBP at PP Week 24 in maternal participants was reported.	PP Week 24
Maternal Participants: Change From Baseline in Vital Sign - Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	Change from baseline in vital signs -SBP and DBP in maternal participants were reported.	Baseline (GA Week 14), GA Week 36, and PP Week 24
Maternal Participants: Absolute Value of Vital Signs - Body Weight at Baseline	Absolute value of vital signs - body weight at baseline in maternal participants was reported.	Baseline (GA Week 14)
Maternal Participants: Absolute Value of Vital Signs - Body Weight at GA Week 36	Absolute value of vital signs -body weight at GA Week 36 in maternal participants was reported.	GA Week 36
Maternal Participants: Absolute Value of Vital Signs - Body Weight at PP Week 24	Absolute value of vital signs included body weight at PP Week 24 in maternal participants was reported.	PP Week 24
Maternal Participants: Change From Baseline in Vital Sign - Body Weight	Change from baseline in vital signs- body weight in maternal participants was reported.	Baseline (GA Week 14), GA Week 36, and PP Week 24
Neonates/Infants: Absolute Value in Vital Signs - Body Temperature at Baseline	Absolute value in vital signs parameter -body temperature at baseline was reported for all neonates/infants.	Baseline (PP Day 0)
Neonates/Infants: Absolute Value of Vital Signs - Body Temperature at PP Week 1	Absolute value of vital signs parameter -body temperature at PP Week 1 was reported for all neonates/infants.	PP Week 1
Neonates/Infants: Absolute Value in Vital Signs - Body Temperature at PP Week 4	Absolute value in vital signs parameter - body temperature at PP Week 4 was reported for all neonates/infants.	PP Week 4
Neonates/Infants: Absolute Value in Vital Signs - Body Temperature at PP Week 24	Absolute value in vital signs parameter -body temperature at PP Week 24 was reported for all neonates/infants.	PP Week 24
Neonates/Infants: Change From Baseline in Vital Signs - Body Temperature	Change from baseline in vital signs- body temperature were reported for all neonates/infants.	Baseline (PP Day 0), PP Weeks 1, 4, and 24
Neonates/Infants: Absolute Value of Vital Signs - Body Weight at Baseline	Absolute value of vital signs parameter- body weight at baseline was reported for all neonates/infants.	Baseline (PP Day 0)
Neonates/Infants: Absolute Value of Vital Signs - Body Weight at PP Week 1	Absolute value of vital signs parameter - body weight at PP Week 1 was reported for all neonates/infants.	PP Week 1
Neonates/Infants: Absolute Value of Vital Signs - Body Weight at PP Week 4	Absolute value of vital signs parameter - body weight at PP Week 4 was reported for all neonates/infants.	PP Week 4
Neonates/Infants: Absolute Value of Vital Signs - Body Weight at PP Week 24	Absolute value of vital signs parameter - body weight at PP Week 24 was reported for all neonates/infants.	PP Week 24
Neonates/Infants: Change From Baseline in Vital Signs -Body Weight	Change from baseline in vital signs - body weight were reported for all neonates/infants.	Baseline (PP Day 0), PP Weeks 1, 4, and 24
Neonates/Infants: Absolute Value of Vital Signs - Respiratory Rate at Baseline	Absolute value of vital signs parameter -respiratory rate at baseline was reported for all neonates/infants.	Baseline (PP Day 0)
Neonates/Infants: Absolute Value of Vital Signs - Respiratory Rate at PP Week 1	Absolute value of vital signs parameter - respiratory rate at PP Week 1 was reported for all neonates/infants.	PP Week 1
Neonates/Infants: Absolute Value of Vital Signs - Respiratory Rate at PP Week 4	Absolute value of vital signs parameter - respiratory rate at PP Week 4 was reported for all neonates/infants.	PP Week 4
Neonates/Infants: Absolute Value of Vital Signs - Respiratory Rate at PP Week 24	Absolute value of vital signs parameter- respiratory rate at PP Week 24 was reported for all neonates/infants.	PP Week 24
Neonates/Infants: Change From Baseline in Vital Signs - Respiratory Rate	Change from baseline in vital signs -respiratory rate was reported for all neonates/infants.	Baseline (PP Day 0), PP Weeks 1, 4, and 24
Neonates/Infants: Absolute Value of Vital Sign - Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline	Absolute value of vital signs parameter - SBP and DBP at baseline were reported for all neonates/infants.	Baseline (PP Day 0)
Neonates/Infants: Absolute Value of Vital Sign - Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at PP Week 1	Absolute value of vital signs parameter - SBP and DBP at PP Week 1 were reported for all neonates/infants.	PP Week 1
Neonates/Infants: Absolute Value of Vital Sign - Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at PP Week 4	Absolute value of vital signs parameter -SBP and DBP at PP Week 4 were reported for all neonates/infants.	PP Week 4
Neonates/Infants: Absolute Value of Vital Sign - Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at PP Week 24	Absolute value of vital signs parameter -SBP and DBP at PP Week 24 were reported for all neonates/infants.	PP Week 24
Neonates/Infants: Change From Baseline in Vital Signs - Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	Change from baseline in vital signs- SBP and DBP were reported for all neonates/infants.	Baseline (PP Day 0), PP Weeks 1, 4, and 24
Percentage of Maternal Participants With Intrauterine Growth Restriction (IUGR) Based on Ultrasound Assessments	Percentage of maternal participants with intrauterine growth restriction (IUGR) based on ultrasound assessments and guidelines from American College of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine was reported. This outcome measure provided the incidence of with IUGR at delivery. IUGR is defined as weight below the 10th percentile for gestational age based on the World Health Organization (WHO) fetal growth curve.	Baseline (GA Week 14), GA Weeks 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36
Percentage of Maternal Participants With Abnormal Amniotic Fluid Values: Amniotic Fluid Index (AFI) at Baseline	Percentage of maternal participants with abnormal amniotic fluid values: amniotic fluid index (AFI) at baseline was reported. The amniotic fluid volume abnormality was categorized as an AFI <5 centimeter (cm) or >24 cm.	Baseline (GA Week 14)
Percentage of Maternal Participants With Abnormal Amniotic Fluid Values: AFI at GA Week 26	Percentage of maternal participants with abnormal amniotic fluid values: AFI at GA Week 26 was reported. The amniotic fluid volume abnormality was categorized as an AFI <5 cm or >24 cm.	GA Week 26
Percentage of Maternal Participants With Abnormal Amniotic Fluid Values: AFI at GA Week 36	Percentage of maternal participants with abnormal amniotic fluid values: AFI at GA Week 36 was reported. The amniotic fluid volume abnormality was categorized as an AFI <5 cm or >24 cm.	GA Week 36
Percentage of Maternal Participants With Abnormal Amniotic Fluid Values: Maximum Vertical Pocket (MVP) at Baseline	Percentage of maternal participants with abnormal amniotic fluid values: maximum vertical pocket (MVP) at baseline was reported. The amniotic fluid volume abnormality was categorized as MVP <2 cm or >8 cm.	From Baseline (GA Week 14)
Percentage of Maternal Participants With Abnormal Amniotic Fluid Values: MVP at GA Week 18	Percentage of maternal participants with abnormal amniotic fluid values: MVP at GA Week 18 was reported. The amniotic fluid volume abnormality was categorized as MVP <2 cm or >8 cm.	GA Week 18
Percentage of Maternal Participants With Abnormal Amniotic Fluid Values: MVP at GA Week 22	Percentage of maternal participants with abnormal amniotic fluid values: MVP at GA Week 22 was reported. The amniotic fluid volume abnormality was categorized as MVP <2 cm or >8 cm.	GA Week 22
Number of Neonates/Infants With Appearance, Pulse, Grimace Response, Activity, Respiration (Apgar) Score	Number of neonates/infants with Apgar score from 1 to 10 minutes of life were reported. The system provided a standardized assessment for infants after delivery. The Apgar score comprises five components: 1) color, 2) heart rate, 3) reflexes, 4) muscle tone, and 5) respiration, each of which is given a score of 0, 1, or 2. The score is reported at 1 minute and 5 minutes after birth for all infants, and at 5-minute intervals thereafter until 20 minutes for infants with a score less than 7. This is using an Apgar scale which ranges from minimum total score of 0 and maximum total score of 10, with higher score representing a better outcome.	1, 5, and 10 minutes after birth at PP Day 0
Number of Maternal Participants With Concomitant Medications and Therapies	Number of maternal participants with concomitant medications and therapies were reported.	From baseline (Gestational Age [GA] Week 14) up to PP Week 24 (up to 50 weeks)
Number of Neonates/Infants With Concomitant Medications and Therapies	Number of neonates/infants with concomitant medications and therapies were reported.	From birth (PP Day 0) up to PP Week 96
Percentage of Maternal Participants With Live Birth at or After Gestational Age (GA) Week 32 and Without an Intrauterine Transfusion (IUT) Throughout Their Entire Pregnancies	Percentage of maternal participants with live birth at or after GA Week 32 and without an IUT throughout their entire pregnancies were reported.	From baseline (GA Week 14) up to GA Week 37

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Maternal Participants With Live Birth	Percentage of maternal participants with live birth were reported.	From baseline (GA Week 14) up to GA Week 37
Percentage of Maternal Participants Without an Intrauterine Transfusion (IUT) Before Gestational Age (GA) Week 24	Percentage of maternal participants without an IUT before GA Week 24 were reported.	From baseline (GA Week 14) up to GA Week 24
Maternal Participants : Gestational Age (GA) at First Intrauterine Transfusion (IUT)	Gestational age (GA) at first IUT for maternal participants were reported.	From baseline (GA Week 14) up to GA Week 37
Median Number of Intrauterine Transfusion (IUT) Per Maternal Participant	Median number of intrauterine transfusion (IUT) per maternal participants were reported.	From baseline (GA Week 14) up to GA Week 37
Frequency of Intrauterine Transfusions (IUTs) on Maternal Participants	Frequency of intrauterine transfusions (IUTs) on maternal participants were reported. Frequency of IUTs was defined as total number of IUTs divided by the (date of delivery - date of first IUT +1)/7.	From baseline (GA Week 14) up to GA Week 37
Percentage of Maternal Participants With Fetal Hydrops in Utero or Post Birth	Percentage of maternal participants with fetal hydrops in utero or post birth were reported.	From baseline (Gestational Age [GA] Week 14) up to PP Week 24 (up to 50 weeks)
Maternal Participants: Gestational Age at Time of Delivery	Gestational age at time of delivery for maternal participants were reported.	From baseline (GA Week 14) up to GA Week 37
Percentage of Neonates Who Required Phototherapy	Percentage of neonates who required phototherapy were reported.	From birth (PP Day 0) up to PP Week 24
Percentage of Neonates Who Required Exchange Transfusions	Percentage of neonates who required exchange transfusions were reported.	From birth (PP Day 0) up to PP Week 24
Duration of Postnatal Phototherapy Required by Neonates	Duration of postnatal phototherapy required by neonates were reported.	From birth (PP Day 0) up to PP Week 24
Percentage of Neonates Who Required Simple Transfusions in the First 12 Weeks of Life	Percentage of neonates who required simple transfusions in the first 12 weeks of life were reported.	From birth (PP Day 0) up to PP Week 12
Number of Simple Transfusions Required by Neonate in the First 12 Weeks of Life	Number of simple transfusions required by neonate in the first 12 weeks of life were reported.	From birth (PP Day 0) up to PP Week 12
Maternal Serum Unoccupied Neonatal Concentration of Participants Fc Receptor [FcRn] Receptor Occupancy (RO) in Monocytes by Nipocalimab	Maternal serum unoccupied neonatal concentration of Participants Fc Receptor [FcRn] receptor occupancy (RO) in Monocytes by nipocalimab were reported.	Baseline (GA Week 14), GA Week 16, GA Week 36, PP Day 0, PP Week 4, and PP Week 24
Serum Unoccupied Concentration of Participants Fc Receptor [FcRn] Receptor Occupancy (RO) in Monocytes of Neonate by Nipocalimab	Serum unoccupied FcRn RO in monocytes of neonate by Nipocalimab were reported.	From birth (PP Day 0) up to PP Week 24
Maternal Participants: Change From Baseline in Serum Concentration of Total Immunoglobulin G (IgG) and Subclasses (IgG1, IgG2, IgG3, IgG4), IgA, IgM, and IgE	Change from baseline in serum concentration of total immunoglobulin G (IgG) and subclasses (IgG1, IgG2, IgG3, IgG4), IgA, IgM, and IgE were reported.	IgG: Baseline (GA Week 14), GA Week 16, GA Week 36, birth (PP Day 0), PP Week 4, and PP Week 24; IgG1, IgG2, IgG3, IgG4, IgA, IgM, and IgE: baseline (GA Week 14), GA Week 36
Neonates/Infants: Change From Baseline in Serum Concentration of Total IgG, IgA, IgM, and IgE	Change from baseline in serum concentration of total IgG, IgA, IgM, and IgE were reported in neonates/infants were reported.	Baseline (PP Day 0), PP Weeks 4, 24, 96
Serum Concentrations of Nipocalimab in Maternal Participants	Serum concentrations of Nipocalimab in maternal participants were reported.	Pre dose and post dose: GA Week 14 and GA Week 24; Birth (PP Day 0), PP Week 4 and PP Week 24
Pediatric Quality of Life Inventory (PedsQL) Total and Sub Scale Score in Neonates/Infants	The 45-item PedsQL infant Scales (ages 13-24 months) included physical functioning, physical symptoms, emotional functioning, social functioning, and cognitive functioning. Health summary score for psychosocial (sum of all items over number of items: emotional, social, cognitive functioning scales) and physical (sum of the items over number of items: physical functioning and symptoms scales), as well as a total score (sum of all items over number of items answered on all scales). Items were reverse-scored and linearly transformed to 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0). PedsQL a validated scale ranging from 0 -100, higher scores = a better quality of life.	PP Week 96
Ages and Stages Questionnaires, Third Edition (ASQ-3) Total Domain Score in Neonates/Infants	The ASQ-3 assesses young child's (2-66 months) development based on age and included 6 questions in each area of child development: communication, gross motor, fine motor, problem solving, and personal-social skills. Parents answered either yes (10 points), sometimes (5 points) or not yet (0 points) to each question to complete ASQ-3 and each domain score could range from 0 to 60 points which higher score signifying stronger development.	At PP 6 month, PP 12 month, and PP 24 month

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• de Winter DP, Moise KJ, Ling LE, Oepkes D, Tiblad E, Joanne Verweij EJT, Smoleniec J, Sachs UJ, Bein G, Kilby MD, Miller RS, Devlieger R, Streisand JB, Bredius RGM, Cafone J, Lam E, Leu JH, Mirza A, Nelson RM, Smith V, Schwartz LB, Tjoa ML, Saeed-Khawaja S, Komatsu Y, Lopriore E. Infant Immunity after Maternal Nipocalimab in Severe Hemolytic Disease of the Fetus and Newborn. NEJM Evid. 2026 Feb;5(2):EVIDoa2500097. doi: 10.1056/EVIDoa2500097. Epub 2026 Jan 27.
• Moise KJ Jr, Ling LE, Oepkes D, Tiblad E, Verweij EJTJ, Lopriore E, Smoleniec J, Sachs UJ, Bein G, Kilby MD, Miller RS, Devlieger R, Audibert F, Emery SP, Markham K, Norton ME, Ocon-Hernandez O, Pandya P, Pereira L, Silver RM, Windrim R, Streisand JB, Leu JH, Mirza A, Smith V, Schwartz LB, Tjoa ML, Saeed-Khawaja S, Komatsu Y, Bussel JB; UNITY Study Group. Nipocalimab in Early-Onset Severe Hemolytic Disease of the Fetus and Newborn. N Engl J Med. 2024 Aug 8;391(6):526-537. doi: 10.1056/NEJMoa2314466.

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2018
• Primary Completion (Actual): August 5, 2024
• Study Completion (Actual): August 5, 2024

Study Registration Dates

• First Submitted: February 7, 2019
• First Submitted That Met QC Criteria: February 12, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Alloimmunization; Pregnant women; HDFN; Isoimmunization; M281; Hemolytic Disease of the Fetus and Newborn; Rhesus Disease; Hemolytic disease due to fetomaternal alloimmunization; Hemolytic disease of the newborn with Kell alloimmunization; Rhesus (Rh) isoimmunization of foetus or newborn; Isoimmunization due to other red cell factors; ABO isoimmunization of foetus or newborn; Haemolytic anaemia due to other unclassified antibodies; Isoimmune; Isoimmunized; Alloimmune; Alloimmunized
• Additional Relevant MeSH Terms: Pathologic Processes; Hemolysis
• Other Study ID Numbers: CR108980; 2017-004958-42 (EudraCT Number); MOM-M281-003 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No