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)

Overview

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.

Interventions

• Drug Nipocalimab
  Nipocalimab will be administered as an intravenous infusion.
• Drug Placebo
  Placebo will be administered as an intravenous infusion.

Primary outcome measures

• Percentage of Pregnancies That did not Result in Fetal Loss, Intrauterine Transfusion (IUT), Hydrops Fetalis, or Neonatal Death [Time frame: From randomization in the study through 4 weeks of age or 41 weeks Postmenstrual Age (PMA) during neonatal period, whichever is later]

Secondary outcome measures (12)

• Number of Participants With Hemolytic Disease of the Fetus and Newborn (HDFN) by Severity [Time frame: 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]
• Time to First Occurrence of IUT or Hydrops Fetalis [Time frame: From randomization to delivery of baby (Up to 38 weeks)]
• Neonatal Mortality and Morbidity Index (NMMI) in Liveborn Neonates [Time frame: Through 38 weeks PMA or at discharge if earlier than 38 weeks PMA]
• Number of IUT's Received During the Pregnancy [Time frame: From randomization to delivery of baby (Up to 38 weeks)]
• Percentage of Pregnancies With Fetal Loss [Time frame: Time to delivery of baby (Up to 38 weeks)]
• Percentage of Pregnancies With Fetal or Neonatal Death [Time frame: Through Week 4 or 41 weeks PMA]
• Percentage of Pregnancies With Hydrops Fetalis [Time frame: Up to 41 weeks PMA]
• Percentage of Pregnancies Receiving IUT During Pregnancy [Time frame: Up to 35 weeks of GA period]
• Gestational Age (GA) at First IUT [Time frame: Up to 35 weeks of GA period]
• Percentage of Pregnancies Receiving >1 IUT During Pregnancy [Time frame: Up to 35 weeks of GA period]
• Percentage of Pregnancies Receiving IUT or HDFN Resulting in Fetal Demise (Less Than) <GA Week 20 [Time frame: Up to 20 weeks]
• Gestational Age at Delivery [Time frame: Up to 38 weeks]

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:

• 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

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 20 centers

• University of California at San Diego — La Jolla
• Kaiser Permanente Los Angeles Medical Center — Los Angeles
• UC Davis School of Medicine — Sacramento
• Childrens Hospital Colorado — Aurora
• University of Miami — Miami
• Advocate Children's Hospital — Park Ridge
• Riley Children s Hospital — Indianapolis
• University of Kentucky Medical Center — Lexington
• … and 12 more centers

United Kingdom · 6 centers

• Birmingham Women's Hospital — Birmingham
• Leeds Teaching Hospitals NHS Trust — Leeds
• Kings College Hospital — London
• St Georges Hospital — London
• St.Mary's Hospital — Manchester
• John Radcliffe Hospital — Oxford

Brazil · 5 centers

• Universidade Federal De Minas Gerais — Belo Horizonte
• Empresa Brasileira de Servicos Hospitalares EBSERH Hospital das Clinicas da UFG — Goiânia
• Instituto de Medicina Integral Professor Fernando Figueira — Recife
• Instituto D Or de Pesquisa e Ensino IDOR — Rio de Janeiro
• Hospital Das Clinicas Da Faculdade De Medicina Da USP — São Paulo

Japan · 5 centers

• Kyushu University Hospital — Fukuoka
• Gifu Prefectural General Medical Center — Gifu
• Osaka Womens and Childrens Hospital — Izumi-shi
• Toho University Medical Center Omori Hospital — Ōta-ku
• Miyagi Childrens Hospital — Sendai

Canada · 4 centers

• BC Women's Hospital University of British Columbia — Vancouver
• Mount Sinai Hospital — Toronto
• Centre Hospitalier Sainte Justine — Montreal
• McGill University Health Centre — Montreal

France · 3 centers

• Hospices Civils de Lyon - Groupement Hospitalier Est - Hopital Femme Mere Enfant — Bron
• CHRU Lille — Lille
• Hopital Armand Trousseau — Paris

Germany · 3 centers

• Charite Universitaetsmedizin Berlin — Berlin
• Universitaetsklinikum Giessen und Marburg Standort Giessen — Giessen
• Universitaetsklinikum Hamburg Eppendorf — Hamburg

Israel · 3 centers

• Hadassah mount scopus — Jerusalem
• Rabin Medical Center — Petah Tikva
• The Chaim Sheba Medical Center — Ramat Gan

Spain · 3 centers

• Hosp Univ Vall D Hebron — Barcelona
• Hosp. Univ. La Paz — Madrid
• Hosp. Virgen Del Rocio — Seville

Argentina · 2 centers

• Hospital Italiano de Buenos Aires — Buenos Aires
• Hospital Privado Universitario De Cordoba — Córdoba

Australia · 2 centers

• Mater Hospital Brisbane — South Brisbane
• Liverpool Hospital — Sydney

Austria · 2 centers

• Medizinische Universitaet Graz — Graz
• Medizinische Universitaet Wien — Vienna

Belgium · 2 centers

• C.H.U. Brugmann — Brussels
• Universitair Ziekenhuis Leuven — Leuven

Ireland · 1 center

• Rotunda Hospital — Dublin

Italy · 1 center

• Fondazione Policlinico Universitario A Gemelli IRCCS — Roma

Netherlands · 1 center

• Leiden University Medical Center — Leiden

Sweden · 1 center

• Karolinska Universitetssjukhuset Huddinge — Stockholm

Publications

• Rego S, Ashimi Balogun O, Emanuel K, Overcash R, Gonzalez JM, Denomme GA, Hoskovec J, King H, Wilson A, Wynn J, Moise KJ Jr. Cell-Free DNA Analysis for the Determination of Fetal Red Blood Cell Antigen Genotype in Individuals With Alloimmunized Pregnancies. Obstet Gynecol. 2024 Oct 1;144(4):436-443. doi: 10.1097/AOG.0000000000005692. Epub 2024 Jul 25. PMID 39053010

Identifiers

NCT: NCT05912517 · CR109199 · 80202135EBF3001 · 2021-002359-12 · 2022-502629-16-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗