A Study of Nipocalimab in Pregnancies at Risk for Severe Hemolytic Disease of the Fetus and Newborn (HDFN)

Phase 3RecruitingNCT05912517

Janssen Research & Development, LLC120 enrolled

Overview

The purpose of this study is to assess the effectiveness of nipocalimab when compared to placebo in decreasing the risk of fetal anemia (a condition in which a baby's red blood cell volume falls below normal levels while the baby is developing in the womb) with live neonates in pregnant participants at risk for severe hemolytic disease of the fetus and newborn.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

120

Conditions

Hemolytic Disease of the Fetus and Newborn

Interventions

NipocalimabDRUG

Nipocalimab will be administered as an intravenous infusion.

PlaceboDRUG

Placebo will be administered as an intravenous infusion.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 45 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Pregnant and an estimated gestational age (GA) (based on ultrasound dating) from Week 13\^0/7 to Week 18\^6/7 at randomization * History of severe Hemolytic Disease of the Fetus and Newborn (HDFN) in a prior pregnancy defined as documented: 1. fetal anemia as result of HDFN or fetal hydrops as result of HDFN or received greater than or equal to (\>=)1 IUT as a result of HDFN or 2. fetal loss or neonatal death as a result of HDFN, with maternal alloantibody titers for Rhesus antigen D protein (RhD), Kell, Kell Rhesus antigen C protein (Rhc), Rhesus antigen E protein (RhE), or RhC antigen above the critical levels (anti-Kell \>=4; other \>=16) and evidence of an antigen-positive fetus * During the current pregnancy, presence of maternal alloantibody to RhD, Rhc, RhE, or RhC antigen with titers above the critical level (anti-Kell \>= 4; other \>=16) based on the designated central lab results at screening * Evidence of antigen-positivity corresponding to the current maternal alloantibody (RhD, Kell, Rhc, RhE, or RhC) confirmed by non-invasive antigen cell-free fetal DNA (cffDNA) performed at the central laboratory * Have screening lab test results within values within the study protocol-specified parameters: a) albumin \>= lower limit of normal (LLN); b) alanine transaminase (AST) less than or equal to (\<=) 2 × upper limit of normal (ULN); c) alanine transaminase (ALT) \<=2 × ULN d) creatinine \<=0.8 milligrams per deciliter (mg/dL), SI: \<=70.7 micromole per liter (μmol/L), and Serum total immunoglobulins G (IgG) ≥ 600 mg/dL SI: \>=6 g/L * Medically stable on the basis of physical examination, medical history, vital signs, 12-lead ECG, and clinical lab tests performed at screening Exclusion Criteria: * Currently pregnant with a multiple gestation (twins or more) * Evidence of fetal anemia prior to randomization in the current pregnancy * History of severe preeclampsia prior to GA Week 34 or severe fetal growth restriction (estimated fetal weight \<3rd percentile, based on local fetal growth normative standards) in a previous pregnancy * Current uncontrolled hypertension * History of myocardial infarction, unstable ischemic heart disease, or stroke * Has any confirmed or suspected clinical immunodeficiency syndrome or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant * Has inflammatory or autoimmune diseases requiring immunosuppressive therapies that may jeopardize the safety of the participant * Currently has a malignancy or has a history of malignancy within 3 years before screening (with the exception of localized basal cell carcinoma and/or squamous cell carcinoma skin cancer that has been adequately treated with no evidence of recurrence for at least 3 months before the first study intervention administration or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before the first study intervention) * Is currently receiving systemic corticosteroids or other immunosuppressants for disorders unrelated to the pregnancy * Has received or planning to receive plasmapheresis, immunoadsorption therapy, intravenous immunoglobulin (IV Ig), or any immunoglobulin (Ig)G fragment crystallizable (Fc)-related protein therapeutics during the current pregnancy * Has a severe infection including opportunistic infections * Presence of abnormal (protocol-specified) hematologic lab values during screening * History of an unprovoked pulmonary embolism or history of recurrent deep vein thrombosis (DVT) The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Locations (59)

Outcomes

Primary Outcomes

Percentage of Pregnancies That did not Result in Fetal Loss, Intrauterine Transfusion (IUT), Hydrops Fetalis, or Neonatal Death

Percentage of pregnancies that did not result in fetal loss, IUT, hydrops fetalis, or neonatal death (during the neonatal period) will be reported. Hydrops fetalis is defined as the presence of greater than or equal to(\>=)2 abnormal fluid collections in the fetus or neonate, such as ascites, pleural effusions, pericardial effusion, and generalized skin edema (skin thickness greater (\>)5 millimeter \[mm\]). PMA is the time elapsed between the first day of the last menstrual period and birth (gestational age) plus the time elapsed after birth (chronological age).

Time frame: From randomization in the study through 4 weeks of age or 41 weeks Postmenstrual Age (PMA) during neonatal period, whichever is later

Secondary Outcomes

Number of Participants With Hemolytic Disease of the Fetus and Newborn (HDFN) by Severity

Number of participants with HDFN by severity will be reported. The severity of HDFN is defined as: 5 (fatal): fetal or neonatal death due to any reason; 4 (severe): hydrops fetalis (in fetus or newborn) or receiving IUT during pregnancy as a result of HDFN but not 5 (fatal); 3 (moderate): neonatal exchange transfusions received as a result of HDFN related hemolysis and jaundice but not 4 (severe) or 5 (fatal); 2 (mild): neonatal simple transfusions received due to HDFN after birth, with or without phototherapy, but not 3 (moderate), 4 (severe), or 5 (fatal); and 1 (minimal or none): not in 2 (mild), 3 (moderate), 4 (severe), or 5 (fatal) as described above. Here database lock implies the last participant has given birth or terminated their pregnancy, completed the Week 4 visit after delivery, and whose neonate has also completed the Week 4 visit (or 41 weeks PMA, whichever is later) or died prior to this timepoint.

Time frame: For first database lock: from randomization in the study through 4 weeks of age or 41 weeks PMA during neonatal period, whichever is later for the first database lock; for second database lock: through 12 weeks after birth

Time to First Occurrence of IUT or Hydrops Fetalis

Time to first occurrence of IUT or hydrops fetalis will be reported.

Central Contacts

Study Contact

CONTACT

844-434-4210 Participate-In-This-Study1@its.jnj.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

University of California at San Diego

La Jolla, California, United States

RECRUITING

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

RECRUITING

UC Davis School of Medicine

Sacramento, California, United States

RECRUITING

Childrens Hospital Colorado

Aurora, Colorado, United States

RECRUITING

Advocate Children's Hospital

Park Ridge, Illinois, United States

RECRUITING

Riley Children s Hospital

Indianapolis, Indiana, United States

RECRUITING

University of Kentucky Medical Center

Lexington, Kentucky, United States

RECRUITING

Johns Hopkins Hospital

Baltimore, Maryland, United States

RECRUITING

Midwest Fetal Care Center

Minneapolis, Minnesota, United States

RECRUITING

Columbia University Medical Center

New York, New York, United States

RECRUITING

...and 49 more locations

Time frame: From randomization to delivery of baby (Up to 38 weeks)

Neonatal Mortality and Morbidity Index (NMMI) in Liveborn Neonates

The NMMI will be assessed with the following categories: fatal: fetal/neonatal death; major morbidity: any of intraventricular hemorrhage grade 3/4, seizures, hypoxic-ischemic encephalopathy, necrotizing enterocolitis stage 2/3, respiratory distress syndrome requiring mechanical ventilation, bronchopulmonary dysplasia requiring oxygen support, or persistent pulmonary hypertension; Minor morbidity: anemia requiring simple transfusion, hyperbilirubinemia requiring an exchange transfusion, hypotension requiring treatment, intraventricular hemorrhage grade 1/2, necrotizing enterocolitis stage 1, or respiratory distress syndrome not requiring mechanical ventilation; None: no major or minor morbidities described above. Hyperbilirubinemia requiring phototherapy will be classified in this category'

Time frame: Through 38 weeks PMA or at discharge if earlier than 38 weeks PMA

Number of IUT's Received During the Pregnancy

Number of IUT's received during the pregnancy will be reported.

Time frame: From randomization to delivery of baby (Up to 38 weeks)

Percentage of Pregnancies With Fetal Loss

Percentage of pregnancies with fetal loss will be reported.

Time frame: Time to delivery of baby (Up to 38 weeks)

Percentage of Pregnancies With Fetal or Neonatal Death

Percentage of pregnancies with fetal or neonatal death (through the neonatal period) as a result of HDFN will be reported.

Time frame: Through Week 4 or 41 weeks PMA

Percentage of Pregnancies With Hydrops Fetalis

Percentage of pregnancies with hydrops fetalis will be reported. Hydrops fetalis is defined as the presence of \>=2 abnormal fluid collections in the fetus or neonate, such as ascites, pleural effusions, pericardial effusion, and generalized skin edema (skin thickness \>5 mm).

Time frame: Up to 41 weeks PMA

Percentage of Pregnancies Receiving IUT During Pregnancy

Percentage of pregnancies receiving IUT during pregnancy will be reported.

Time frame: Up to 35 weeks of GA period

Gestational Age (GA) at First IUT

GA at first IUT will be reported.

Time frame: Up to 35 weeks of GA period

Percentage of Pregnancies Receiving >1 IUT During Pregnancy

Percentage of pregnancies receiving \>1 IUT during pregnancy will be reported.

Time frame: Up to 35 weeks of GA period

Percentage of Pregnancies Receiving IUT or HDFN Resulting in Fetal Demise (Less Than) <GA Week 20

Percentage of pregnancies receiving IUT or HDFN resulting in fetal demise \<GA Week 20 will be reported.

Time frame: Up to 20 weeks

Gestational Age at Delivery

Gestational age at delivery will be reported.

Time frame: Up to 38 weeks

Percentage of Pregnancies With Neonatal Death Through the Neonatal Period

Percentage of pregnancies with neonatal death through the neonatal period will be reported.

Time frame: From randomization in the study through 4 weeks of age or 41 weeks PMA during neonatal period, whichever is later

Percentage of Liveborn Neonates With HDFN-related Morbidities Other Than Anemia and Hyperbilirubinemia or Jaundice

Percentage of liveborn neonates with HDFN-related morbidities other than anemia and hyperbilirubinemia or jaundice will be reported.

Time frame: From day of birth up to 4 weeks

Absolute Weight of Liveborn Neonates or Infants

Absolute weight of liveborn neonates or infants will be reported.

Time frame: Up to 104 weeks

Change From Baseline in Weight of Liveborn Neonates or Infants

Change from baseline in weight of liveborn neonates or infants will be reported.

Time frame: Baseline to up to 104 weeks

Liveborn Neonates Length of Stay in Neonatal Intensive Care Unit

Liveborn neonates length of stay in neonatal intensive care unit will be reported.

Time frame: From day of birth up to 27 days

Percentage of Liveborn Neonates Receiving Exchange Transfusions for HDFN

Percentage of liveborn neonates receiving exchange transfusions for HDFN will be reported.

Time frame: From day of birth up to 27 days

Number of Neonatal Exchange Transfusions per Liveborn Neonate

Number of neonatal exchange transfusions per liveborn neonate will be reported.

Time frame: From day of birth up to 27 days

Percentage of Liveborn Neonates or Infants with Simple Transfusions for HDFN

Percentage of liveborn neonates or infants with simple transfusions for HDFN through the neonatal period (for the first database lock) or 12 weeks (for the second database lock) after birth will be reported.

Time frame: For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks

Number of Simple Transfusions for HDFN per Liveborn Neonate or Infant

Number of simple transfusions for HDFN per liveborn neonate or infant through the neonatal period (for the first database lock) or 12 weeks (for the second database lock) after birth will be reported.

Time frame: For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks

Percentage of Liveborn Neonates With Hyperbilirubinemia Treated With Phototherapy

Percentage of liveborn neonates with hyperbilirubinemia treated with phototherapy will be reported.

Time frame: From day of birth up to 27 days

Number of Days of Phototherapy Received for Hyperbilirubinemia per Liveborn Neonate

Number of days of phototherapy received for hyperbilirubinemia per liveborn neonate will be reported.

Time frame: From day of birth up to 27 days

Percentage of Liveborn Neonates or Infants Receiving Intravenous Immunoglobulin (IVIg) for HDFN Treatment

Percentage of liveborn neonates or infants receiving IVIg for HDFN treatment will be reported.

Time frame: For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks

Number of Maternal Deaths

Number of maternal deaths will be reported.

Time frame: Form randomization up to 24 weeks postpartum

Number of Participants with Adverse Events (AEs)

Number of participants with AEs, serious adverse events, and AEs of special interest (AESIs), AE's leading to discontinuations, infections, serious infections, infusion reactions, and hypersensitivity reactions will be reported. Treatment-emergent adverse events associated with the following situations are considered as AESIs: hypoalbuminemia, clinically significant bleeding with a corresponding placental finding on ultrasound, maternal infections that led to clinically significant morbidities or mortalities in fetus or neonates, Infections that are severe or require intravenous (IV) anti-infective or operative or invasive intervention in maternal participants or neonates or infants, and infants with hypogammaglobulinemia.

Time frame: From randomization up to 24 weeks postpartum

Number of Maternal Pregnancy Complications

Number of maternal pregnancy complications will be reported.

Time frame: Up to 38 weeks

Number of IUT Related complications

Number of participants with IUT related complications will be reported.

Time frame: Up to 35 weeks of GA period

Percentage of Pregnancies With Cesarean Delivery, Preterm Birth, Fetal Growth, and Preeclampsia

Percentage of pregnancies with cesarean delivery, cesarean delivery due to IUT complications, preterm birth \<GA week 28, preterm birth \<GA week 32, preterm birth \<GA week 34, preterm birth \<GA week 37, fetal growth restriction, and preeclampsia will be reported.

Time frame: Up to 38 weeks of GA period

Percentage of Liveborn Neonates or Infants Who Died

Percentage of liveborn neonates or infants who died will be reported.

Time frame: Up to 104 weeks

Percentage of Liveborn Neonates or Infants With AEs

Percentage of liveborn neonates or infants with AEs, SAEs, AESIs, infections, serious infections will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. Any event requiring hospitalization (or prolongation of hospitalization) that occurs during participation in the study must be reported as an SAE.

Time frame: Up to 104 weeks

Percentage of Liveborn Neonates or Infants Receiving IVIg for Non-HDFN Indications

Percentage of liveborn neonates or infants receiving IVIg for non-HDFN indications will be reported.

Time frame: Up to 104 weeks

Percentage of Liveborn Neonates or Infants With Abnormal Hearing

Percentage of liveborn neonates or infants with abnormal hearing will be reported.

Time frame: Up to 104 weeks

Bayley Scales of Infant Development and Toddler Development

The Bayley Scales of infant development is considered the standard assessment of early child development and includes cognition, language, motor skills, social emotional, and adaptive behavior will be reported. The Bayley Scales (3rd edition) are reference standards that measure infant and toddler development in five areas: cognition, language, motor skills, social-emotional and adaptive behavior. The cognition, language and motor skills scales are directly administered to the infant, while social-emotional, and adaptive behavior scales are caregiver questionnaires. The scores are standardized using norm reference samples with representative demographics and age adjusted for prematurity. Higher scores in the Bayley Scales indicate better outcomes.

Time frame: Week 52 and 104

Change From Baseline in Generalized Anxiety Disorder 7-Item (GAD7) Over time During Pregnancy and Postpartum

Change from baseline in GAD7 over time during pregnancy and postpartum will be reported. The GAD-7 scale is a self-administered questionnaire designed to measure anxiety. The recall period for all items is the past 2 weeks. Responses to all items are rated on a 4-point Likert scale ranging from 0 "not at all" to 3 "nearly every day". The total score ranges from 0 to 21, with higher scores indicating higher severity of anxiety symptoms.

Time frame: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum

Change From Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Domain Score

Change from baseline in SF-36v2 acute form domain score will be reported. The SF-36 version 2 acute is a self-administered, 36-item questionnaire measuring health-related quality of life and includes 8 domains that measure physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality social functioning, role limitations due to emotional problems, and mental health. The 8 domains can be aggregated into 2 summary scales that reflect physical and mental health: a physical component summary and a mental component summary. Responses to all items are rated on a 3, 5, or 6-point Likert scale, with higher scores indicating better health status.

Time frame: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum

Change From Baseline in EuroQol Five-dimension Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) Score

Change from baseline in EQ-5D-5L visual analogue score will be reported. The EQ-5D descriptive system is comprised of 5 items across the following 5 dimensions: mobility, self-care, usual activities, pain or discomfort and anxiety or depression. The EQ-5D-5L uses a 5-point Likert response scale ranging from "no problems" to "extreme problems", with higher scores indicating better quality of life. EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ-VAS). EQ-VAS score ranges from 0 to 100, where 0 = worst imaginable health state and 100 = best imaginable health state. Higher score indicates good health state.

Time frame: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum

Change From Baseline in EuroQol 5-Dimension Descriptive (EQ-5D) Index Score

Change from baseline in EQ-5D index score will be reported. The EQ-5D descriptive system is comprised of 5 items across the following 5 dimensions: mobility, self-care, usual activities, pain or discomfort and anxiety or depression. The EQ-5D-5L descriptive system uses a 5-point Likert response scale ranging from "no problems" to "extreme problems", with higher scores indicating better quality of life.

Time frame: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum

Infant Health-Related Quality of Life Instrument (IQI) Score for Neonate or Infant Overtime

IQI score for neonate or infant will be reported. The IQI consists of 7 health attributes including sleeping, feeding, breathing, stooling or poo, mood, skin, and interaction. Responses to all items are rated on a 4-point Likert scale, with higher scores indicating better quality of life.

Time frame: Weeks 4, 8 and 52