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

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 3

Conditions: Hemolytic Disease of the Fetus and Newborn

Treatments: Drug: Nipocalimab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05912517

2021-002359-12 (EudraCT Number)

2022-502629-16-00 (Registry Identifier)

CR109199

80202135EBF3001 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 120 estimated patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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120 participants in 2 patient groups, including a placebo group

Nipocalimab

Experimental group

Description:

Participants will receive nipocalimab intravenously (IV) once weekly (qw) from randomization through gestational age (GA) Week 35.

Treatment:

Drug: Nipocalimab

Placebo

Placebo Comparator group

Description:

Participants will receive matching placebo IV qw from randomization through GA Week 35.

Treatment:

Drug: Placebo