Clinical trial NCT05912517: A Study of Nipocalimab in Pregnancies at Risk for Severe Hemolytic Disease of the Fetus and Newborn (HDFN)
Official title: A Phase 3 Randomized, Placebo-Controlled, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Nipocalimab in Pregnancies at Risk for Severe Hemolytic Disease of the Fetus and Newborn (HDFN)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hemolytic Disease of the Fetus and Newborn
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2023-06-22
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The participants will be randomized in a 2:1 to receive nipocalimab and placebo treatment.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Pregnancies That did not Result in Fetal Loss, Intrauterine Transfusion (IUT), Hydrops Fetalis, or Neonatal Death
timeFrame: From randomization in the study through 4 weeks of age or 41 weeks Postmenstrual Age (PMA) during neonatal period, whichever is later
Secondary outcomes:
measure: Number of Participants With Hemolytic Disease of the Fetus and Newborn (HDFN) by Severity
timeFrame: 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
measure: Time to First Occurrence of IUT or Hydrops Fetalis
timeFrame: From randomization to delivery of baby (Up to 38 weeks)
measure: Neonatal Mortality and Morbidity Index (NMMI) in Liveborn Neonates
timeFrame: Through 38 weeks PMA or at discharge if earlier than 38 weeks PMA
measure: Number of IUT's Received During the Pregnancy
timeFrame: From randomization to delivery of baby (Up to 38 weeks)
measure: Percentage of Pregnancies With Fetal Loss
timeFrame: Time to delivery of baby (Up to 38 weeks)
measure: Percentage of Pregnancies With Fetal or Neonatal Death
timeFrame: Through Week 4 or 41 weeks PMA
measure: Percentage of Pregnancies With Hydrops Fetalis
timeFrame: Up to 41 weeks PMA
measure: Percentage of Pregnancies Receiving IUT During Pregnancy
timeFrame: Up to 35 weeks of GA period
measure: Gestational Age (GA) at First IUT
timeFrame: Up to 35 weeks of GA period
measure: Percentage of Pregnancies Receiving >1 IUT During Pregnancy
timeFrame: Up to 35 weeks of GA period
measure: Percentage of Pregnancies Receiving IUT or HDFN Resulting in Fetal Demise (Less Than) <GA Week 20
timeFrame: Up to 20 weeks
measure: Gestational Age at Delivery
timeFrame: Up to 38 weeks
measure: Percentage of Pregnancies With Neonatal Death Through the Neonatal Period
timeFrame: From randomization in the study through 4 weeks of age or 41 weeks PMA during neonatal period, whichever is later
measure: Percentage of Liveborn Neonates With HDFN-related Morbidities Other Than Anemia and Hyperbilirubinemia or Jaundice
timeFrame: From day of birth up to 4 weeks
measure: Absolute Weight of Liveborn Neonates or Infants
timeFrame: Up to 104 weeks
measure: Change From Baseline in Weight of Liveborn Neonates or Infants
timeFrame: Baseline to up to 104 weeks
measure: Liveborn Neonates Length of Stay in Neonatal Intensive Care Unit
timeFrame: From day of birth up to 27 days
measure: Percentage of Liveborn Neonates Receiving Exchange Transfusions for HDFN
timeFrame: From day of birth up to 27 days
measure: Number of Neonatal Exchange Transfusions per Liveborn Neonate
timeFrame: From day of birth up to 27 days
measure: Percentage of Liveborn Neonates or Infants with Simple Transfusions for HDFN
timeFrame: For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks
measure: Number of Simple Transfusions for HDFN per Liveborn Neonate or Infant
timeFrame: For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks
measure: Percentage of Liveborn Neonates With Hyperbilirubinemia Treated With Phototherapy
timeFrame: From day of birth up to 27 days
measure: Number of Days of Phototherapy Received for Hyperbilirubinemia per Liveborn Neonate
timeFrame: From day of birth up to 27 days
measure: Percentage of Liveborn Neonates or Infants Receiving Intravenous Immunoglobulin (IVIg) for HDFN Treatment
timeFrame: For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks
measure: Number of Maternal Deaths
timeFrame: Form randomization up to 24 weeks postpartum
measure: Number of Participants with Adverse Events (AEs)
timeFrame: From randomization up to 24 weeks postpartum
measure: Number of Maternal Pregnancy Complications
timeFrame: Up to 38 weeks
measure: Number of IUT Related complications
timeFrame: Up to 35 weeks of GA period
measure: Percentage of Pregnancies With Cesarean Delivery, Preterm Birth, Fetal Growth, and Preeclampsia
timeFrame: Up to 38 weeks of GA period
measure: Percentage of Liveborn Neonates or Infants Who Died
timeFrame: Up to 104 weeks
measure: Percentage of Liveborn Neonates or Infants With AEs
timeFrame: Up to 104 weeks
measure: Percentage of Liveborn Neonates or Infants Receiving IVIg for Non-HDFN Indications
timeFrame: Up to 104 weeks
measure: Percentage of Liveborn Neonates or Infants With Abnormal Hearing
timeFrame: Up to 104 weeks
measure: Bayley Scales of Infant Development and Toddler Development
timeFrame: Week 52 and 104
measure: Change From Baseline in Generalized Anxiety Disorder 7-Item (GAD7) Over time During Pregnancy and Postpartum
timeFrame: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
measure: Change From Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Domain Score
timeFrame: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
measure: Change From Baseline in EuroQol Five-dimension Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) Score
timeFrame: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
measure: Change From Baseline in EuroQol 5-Dimension Descriptive (EQ-5D) Index Score
timeFrame: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
measure: Infant Health-Related Quality of Life Instrument (IQI) Score for Neonate or Infant Overtime
timeFrame: Weeks 4, 8 and 52
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis School of Medicine
state: California
city: Aurora
country: United States
facility: Childrens Hospital Colorado
state: Colorado
city: Park Ridge
country: United States
facility: Advocate Children's Hospital
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Minneapolis
country: United States
facility: Midwest Fetal Care Center
state: Minnesota
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina (UNC) - School of Medicine
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Austin
country: United States
facility: University of Texas Dell Medical School Department of Women's Health
state: Texas
city: Galveston
country: United States
facility: University Of Texas Medical Branch At Galveston
state: Texas
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Cordoba
country: Argentina
facility: Hospital Privado Universitario De Cordoba
city: South Brisbane
country: Australia
facility: Mater Hospital Brisbane
city: Sydney
country: Australia
facility: Liverpool Hospital
city: Vienna
country: Austria
facility: Medizinische Universitaet Wien
city: Bruxelles
country: Belgium
facility: C.H.U. Brugmann
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
city: Belo Horizonte
country: Brazil
facility: Universidade Federal De Minas Gerais
city: Goiania
country: Brazil
facility: Empresa Brasileira de Servicos Hospitalares EBSERH Hospital das Clinicas da UFG
city: Recife
country: Brazil
facility: Instituto de Medicina Integral Professor Fernando Figueira
city: Rio de Janeiro
country: Brazil
facility: Instituto D Or de Pesquisa e Ensino IDOR
city: Sao Paulo
country: Brazil
facility: Hospital Das Clinicas Da Faculdade De Medicina Da USP
city: Vancouver
country: Canada
facility: BC Women's Hospital University of British Columbia
state: British Columbia
city: Montreal
country: Canada
facility: Centre Hospitalier Sainte Justine
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Lille Cedex
country: France
facility: CHRU Lille
city: Paris
country: France
facility: Hopital Armand Trousseau
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin
city: Giessen
country: Germany
facility: Universitaetsklinikum Giessen und Marburg Standort Giessen
city: Dublin
country: Ireland
facility: Rotunda Hospital
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli IRCCS
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Gifu
country: Japan
facility: Gifu Prefectural General Medical Center
city: Izumi-shi
country: Japan
facility: Osaka Women's and Children's Hospital
city: Ota
country: Japan
facility: Toho University Medical Center Omori Hospital
city: Sendai
country: Japan
facility: Miyagi Children's Hospital
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Huddinge
city: Birmingham
country: United Kingdom
facility: Birmingham Women's Hospital
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: St George's Hospital
city: Manchester
country: United Kingdom
facility: St.Mary's Hospital
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: