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A Study of Nipocalimab or Intravenous Immunoglobulin (IVIG) in Pregnancies At Risk of Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)

Phase 3
Recruiting
Conditions
Thrombocytopenia, Neonatal Alloimmune
Interventions
Drug: Intravenous immunoglobulins (IVIG)
Registration Number
NCT06533098
Lead Sponsor
Janssen Research & Development, LLC
Brief Summary

The purpose of this study is to assess the efficacy and safety of nipocalimab in reducing the risk of severe fetal and neonatal alloimmune thrombocytopenia (FNAIT).

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
50
Inclusion Criteria
  • Pregnant and an estimated gestational age from week 13 to 18 at visit 1
  • Has a history of greater than or equal to (>=) 1 prior pregnancy with FNAIT based on medical records including: a) neonatal platelet count less than (<) 150*10^9/Liter with no fetal/neonatal intracranial hemorrhage (ICH) or severe fetal/neonatal hemorrhage (standard-risk) OR b) fetus/neonate with ICH or severe hemorrhage in a fetus/neonate (high-risk)
  • Current pregnancy with presence of maternal anti-HPA-1a and/or anti-HPA-5b alloantibody and positive fetal HPA-1a and/or HPA-5b genotype as confirmed by cell-free fetal DNA in maternal blood
  • Health status considered stable by the investigator based on physical examination, medical history, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests performed at screening
  • For maternal participant and neonate/infant, willing to forego participation in another clinical study of an investigational therapy until the last follow-up visit
Exclusion Criteria
  • Currently pregnant with multiple gestations (twins or more)
  • History of severe preeclampsia in a previous pregnancy
  • History of myocardial infarction, unstable ischemic heart disease, or stroke
  • Known allergies, hypersensitivity, or intolerance to nipocalimab or its excipients, to IVIG or to prednisone
  • Has any confirmed or suspected clinical immunodeficiency syndrome or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 1: NipocalimabNipocalimabMaternal participants with alloantibodies against HPA-1a and/or HPA-5b will be randomized to receive nipocalimab starting at gestational age (GA) week 13 to 18 until before delivery.
Arm 2: Intravenous Immunoglobins (IVIG)Intravenous immunoglobulins (IVIG)Maternal participants with alloantibodies against HPA-1a and/or HPA-5b will be randomized to receive IVIG from GA week 12 for high-risk pregnancies or GA week 20 for standard-risk pregnancies. Additionally, prednisone will be added per study protocol.
Arm 2: Intravenous Immunoglobins (IVIG)PrednisoneMaternal participants with alloantibodies against HPA-1a and/or HPA-5b will be randomized to receive IVIG from GA week 12 for high-risk pregnancies or GA week 20 for standard-risk pregnancies. Additionally, prednisone will be added per study protocol.
Primary Outcome Measures
NameTimeMethod
Fetus/Neonate with Outcome of Death or Adjudicated Severe Bleeding or Platelet Count Less Than (<) 30*10^9/LUp to 1 Week post birth

Outcome of fetus/neonate death or adjudicated severe bleeding up to the first week post birth or platelet count \<30\*10\^9/L will be reported.

Secondary Outcome Measures
NameTimeMethod
Platelet Count at Birth in a NeonateAt birth

Platelet count at birth in a neonate will be reported.

Neonate/Fetus with Outcome of DeathUp to 1 Week post birth

Fetus/neonate with outcome of death will be reported.

Neonate with Platelet Count at Birth <10*10^9/LAt birth

Platelet count at birth \<10\*10\^9/L in a neonate will be reported.

Neonate with Platelet Count at Birth <30*10^9/LAt birth

Platelet count at birth \<30\*10\^9/L in a neonate will be reported.

Neonate with Platelet Count at Birth <50*10^9/LAt birth

Platelet count at birth \<50\*10\^9/L in a neonate will be reported.

Neonate with Platelet Count at Birth <150*10^9/LAt birth

Platelet count at birth \<150\*10\^9/L in a neonate will be reported.

Nadir Platelet Count in a NeonateUp to 1 Week post birth

Nadir platelet count in a neonate will be reported.

Neonate Requiring Platelet TransfusionUp to 1 Week post birth

Neonate who require at least one platelet transfusion will be reported.

Number of Platelet Transfusions in NeonateUp to 1 Week post birth

Number of platelet transfusions per neonate will be reported.

Number of Donor Exposures for Platelet Transfusions in NeonateUp to 1 Week post birth

Number of donor exposures for a neonate who received at least one platelet transfusion will be reported.

Neonate/Fetus With Adjudicated BleedingUp to 1 Week post birth

Neonate/Fetus with adjudicated bleeding will be reported.

Neonate Requiring Postnatal Intravenous Immunoglobulin (IVIG) for the Treatment of ThrombocytopeniaUp to 1 Week post birth

Neonate requiring IVIG for the treatment of thrombocytopenia will be reported.

Maternal Participant with TEAE Leading to Discontinuation of Study InterventionUp to Week 24

Maternal participant with TEAE leading to discontinuation of study intervention will be reported.

Neonate/Infant With TEAE, SAE and AESIFrom Day of birth to Week 104

Neonate/infant with TEAE, SAE and AESI will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the intervention under study.

Fetus/Neonate with a TEAE of BleedingFrom Day of birth to Week 104

Fetus/Neonate with a TEAE of bleeding will be reported.

Neonate with a TEAE of InfectionFrom Day of birth to Week 104

Neonate with a TEAE of infection will be reported.

Maternal Participant with Treatment-Emergent Adverse Events (TEAE), Serious Adverse Events (SAE) and Adverse Event of Special Interest (AESI)Up to Week 24

Maternal participant with TEAE, SAE and AESI will be reported. An Adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the intervention under study.

Bayley Scales Assessment for Infant DevelopmentAt Week 52 and Week 104

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.

Maternal Participants with Incidence of Antibodies to NipocalimabUp to Week 4

Incidence of antibodies to nipocalimab including neutralizing antibodies in maternal serum during pregnancy and postpartum will be reported.

Trial Locations

Locations (12)

Universitaetsklinikum Tuebingen

🇩🇪

Tuebingen, Germany

John Radcliffe Hospital

🇬🇧

Oxford, United Kingdom

Medizinische Universitaet Graz

🇦🇹

Graz, Austria

Medical University Vienna

🇦🇹

Vienna, Austria

Universitaetsklinikum Giessen und Marburg GmbH

🇩🇪

Giessen, Germany

Universitatsklinikum Jena

🇩🇪

Jena, Germany

Instytut Centrum Zdrowia Matki Polki

🇵🇱

Lodz, Poland

Instytut Matki i Dziecka

🇵🇱

Warszawa, Poland

Panstwowy Instytut Medyczny MSWiA w Warszawie

🇵🇱

Warszawa, Poland

Birmingham Women's Hospital

🇬🇧

Birmingham, United Kingdom

Liverpool Women's NHS Foundation Trust - Liverpool Women's Hospital

🇬🇧

Liverpool, United Kingdom

Queen Charlotte's and Chelsea Hospital

🇬🇧

London, United Kingdom

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