NCT05912517招募中3 期
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)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 112
- 主要终点
- Percentage of Pregnancies That did not Result in Fetal Loss, Intrauterine Transfusion (IUT), Hydrops Fetalis, or Neonatal Death
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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:
- •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
- •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
排除标准
- •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.
研究组 & 干预措施
Placebo
Placebo Comparator
Participants will receive matching placebo IV qw from randomization through GA Week 35.
干预措施: Placebo (Drug)
Nipocalimab
Experimental
Participants will receive nipocalimab intravenously (IV) once weekly (qw) from randomization through gestational age (GA) Week 35.
干预措施: Nipocalimab (Drug)
结局指标
主要结局
Percentage of Pregnancies That did not Result in Fetal Loss, Intrauterine Transfusion (IUT), Hydrops Fetalis, or Neonatal Death
时间窗: From randomization in the study through 4 weeks of age or 41 weeks Postmenstrual Age (PMA) during neonatal period, whichever is later
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).
次要结局
- Percentage of Pregnancies With Hydrops Fetalis(Up to 41 weeks PMA)
- Number of IUT's Received During the Pregnancy(From randomization to delivery of baby (Up to 38 weeks))
- Gestational Age at Delivery(Up to 38 weeks)
- Time to First Occurrence of IUT or Hydrops Fetalis(From randomization to delivery of baby (Up to 38 weeks))
- Percentage of Pregnancies Receiving IUT During Pregnancy(Up to 35 weeks of GA period)
- Gestational Age (GA) at First IUT(Up to 35 weeks of GA period)
- Percentage of Pregnancies Receiving IUT or HDFN Resulting in Fetal Demise (Less Than) <GA Week 20(Up to 20 weeks)
- Absolute Weight of Liveborn Neonates or Infants(Up to 104 weeks)
- Number of Maternal Deaths(Form randomization up to 24 weeks postpartum)
- Percentage of Liveborn Neonates or Infants Who Died(Up to 104 weeks)
- Change From Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Domain Score(Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum)
- Percentage of Pregnancies With Fetal Loss(Time to delivery of baby (Up to 38 weeks))
- Percentage of Pregnancies With Fetal or Neonatal Death(Through Week 4 or 41 weeks PMA)
- Percentage of Pregnancies Receiving >1 IUT During Pregnancy(Up to 35 weeks of GA period)
- Percentage of Liveborn Neonates With HDFN-related Morbidities Other Than Anemia and Hyperbilirubinemia or Jaundice(From day of birth up to 4 weeks)
- Number of Simple Transfusions for HDFN per Liveborn Neonate or Infant(For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks)
- Number of Maternal Pregnancy Complications(Up to 38 weeks)
- Percentage of Liveborn Neonates or Infants Receiving IVIg for Non-HDFN Indications(Up to 104 weeks)
- Number of Participants With Hemolytic Disease of the Fetus and Newborn (HDFN) by Severity(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)
- Neonatal Mortality and Morbidity Index (NMMI) in Liveborn Neonates(Through 38 weeks PMA or at discharge if earlier than 38 weeks PMA)
- Number of Days of Phototherapy Received for Hyperbilirubinemia per Liveborn Neonate(From day of birth up to 27 days)
- Number of IUT Related complications(Up to 35 weeks of GA period)
- Percentage of Pregnancies With Cesarean Delivery, Preterm Birth, Fetal Growth, and Preeclampsia(Up to 38 weeks of GA period)
- Percentage of Liveborn Neonates or Infants With AEs(Up to 104 weeks)
- Percentage of Pregnancies With Neonatal Death Through the Neonatal Period(From randomization in the study through 4 weeks of age or 41 weeks PMA during neonatal period, whichever is later)
- Change From Baseline in Weight of Liveborn Neonates or Infants(Baseline to up to 104 weeks)
- Percentage of Liveborn Neonates Receiving Exchange Transfusions for HDFN(From day of birth up to 27 days)
- Number of Neonatal Exchange Transfusions per Liveborn Neonate(From day of birth up to 27 days)
- Percentage of Liveborn Neonates or Infants with Simple Transfusions for HDFN(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(From day of birth up to 27 days)
- Percentage of Liveborn Neonates or Infants Receiving Intravenous Immunoglobulin (IVIg) for HDFN Treatment(For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks)
- Change From Baseline in EuroQol Five-dimension Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) Score(Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum)
- Change From Baseline in EuroQol 5-Dimension Descriptive (EQ-5D) Index Score(Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum)
- Liveborn Neonates Length of Stay in Neonatal Intensive Care Unit(From day of birth up to 27 days)
- Number of Participants with Adverse Events (AEs)(From randomization up to 24 weeks postpartum)
- Percentage of Liveborn Neonates or Infants With Abnormal Hearing(Up to 104 weeks)
- Change From Baseline in Generalized Anxiety Disorder 7-Item (GAD7) Over time During Pregnancy and Postpartum(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(Weeks 4, 8 and 52)
- Bayley Scales of Infant Development and Toddler Development(Week 52 and 104)
研究者
研究点 (112)
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