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)
Hemolytic disease of fetus and newborn (HDFN)
The total duration of this study is up to 135 weeks which includes an up to 9-week screening period, an up to 23-week treatment period, and a safety follow-up period of up to 6 months for the pregnant individual and up to 2 years for the baby after birth. At the beginning of the treatment period, participants will be randomly (like a flip of a coin) divided into one of two treatment groups: Group 1: receive nipocalimab intravenously (IV) once weekly (qw) from randomization through gestational age (GA) Week 35. Group 2: receive matching placebo IV qw from randomization through GA Week 35.
Current inclusion criteria as of 02/07/2025: 1. Pregnant and an estimated gestational age (GA) (based on ultrasound dating) from Week 13 and 0/7 days to 18 weeks and 6/7 days at randomisation 2. History of severe Hemolytic Disease of the Fetus and Newborn (HDFN) in a prior pregnancy defined as: 2.1. documented 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 2.2. 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 3. 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 4. 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. 5. Have screening laboratory values within the study protocol-specified parameters: 5.1. albumin >= lower limit of normal (LLN) 5.2. alanine transaminase (AST) less than or equal to (<=) 2 × upper limit of normal (ULN) 5.3. alanine transaminase (ALT) <=2 × ULN 5.4. 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 6. Medically stable on the basis of physical examination, medical history, vitalsigns, 12-lead ECG, and clinical laboratory tests performed at screening Previous inclusion criteria: 1. Pregnant and an estimated gestational age (GA) (based on ultrasound dating) from Week 13 and 0/7 days to Week 16 and 6/7 days at randomization 2. History of severe Hemolytic Disease of the Fet
1. Currently pregnant with a multiple gestation (twins or more) 2. Evidence of fetal anemia prior to randomization in the current pregnancy 3. Current uncontrolled hypertension 4. History of myocardial infarction, unstable ischemic heart disease, or stroke 5. Has any confirmed or suspected clinical immunodeficiency syndrome or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant 6. Has inflammatory or autoimmune diseases requiring immunosuppressive therapies that may jeopardize the safety of the participant 7. 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 8. Is currently receiving systemic corticosteroids or other immunosuppressants for disorders unrelated to the pregnancy 9. Has received or planning to receive plasmapheresis, immunoadsorption therapy, intravenous immunoglobulin (IVIg), or any immunoglobulin (Ig)G fragment crystallizable (Fc)-related protein therapeutics during the current pregnancy 10. Has a severe infection including opportunistic infections 11. Presence of abnormal (protocol-specified) hematologic laboratory values during screening 12. 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 Added 02/07/2025: 13. 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.