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

NCT05912517 | Recruiting Phase 3 DMC FDA Drug

• 4 other identifiers: CR10919980202135EBF30012021-002359-122022-502629-16-00
• Study Type: interventional
• Target: 120
• Locations: 16 countries
• Sites: 58

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.

Conditions

Hemolytic Disease of the Fetus and Newborn

Outcome Measures

Primary Outcomes (1)

• Percentage of Pregnancies That did not Result in Fetal Loss, Intrauterine Transfusion (IUT), Hydrops Fetalis, or Neonatal Death

  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).

  From randomization in the study through 4 weeks of age or 41 weeks Postmenstrual Age (PMA) during neonatal period, whichever is later

Secondary Outcomes (39)

• 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

• Time to First Occurrence of IUT or Hydrops Fetalis

  From randomization to delivery of baby (Up to 38 weeks)

• Neonatal Mortality and Morbidity Index (NMMI) in Liveborn Neonates

  Through 38 weeks PMA or at discharge if earlier than 38 weeks PMA

• Number of IUT's Received During the Pregnancy

  From randomization to delivery of baby (Up to 38 weeks)

• Percentage of Pregnancies With Fetal Loss

  Time to delivery of baby (Up to 38 weeks)

Study Arms (2)

Nipocalimab

EXPERIMENTAL

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

Drug: Nipocalimab

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Nipocalimab DRUG

Nipocalimab will be administered as an intravenous infusion.

Also known as: JNJ-80202135, M281, JNJ-86507083

Nipocalimab

Placebo DRUG

Placebo will be administered as an intravenous infusion.

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (60)

University of California at San Diego

La Jolla, California, 92037, United States

RECRUITING

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

RECRUITING

UC Davis School of Medicine

Sacramento, California, 95817, United States

RECRUITING

Childrens Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Advocate Children's Hospital

Park Ridge, Illinois, 60068, United States

RECRUITING

Riley Children s Hospital

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

RECRUITING

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

RECRUITING

Midwest Fetal Care Center

Minneapolis, Minnesota, 55404, United States

RECRUITING

Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

University of North Carolina (UNC) - School of Medicine

Chapel Hill, North Carolina, 27599-7516, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45267, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

Lehigh Valley Hospital

Allentown, Pennsylvania, 18103-6218, United States

RECRUITING

University of Texas Dell Medical School Department of Women's Health

Austin, Texas, 78723, United States

RECRUITING

University Of Texas Medical Branch At Galveston

Galveston, Texas, 77555, United States

RECRUITING

Macon & Joan Brock Virginia Health Sciences at Old Dominion University

Norfolk, Virginia, 23507, United States

RECRUITING

Hospital Italiano de Buenos Aires

Buenos Aires, C1199, Argentina

RECRUITING

Hospital Privado Universitario De Cordoba

Córdoba, X5016KEH, Argentina

RECRUITING

Mater Hospital Brisbane

South Brisbane, 4101, Australia

RECRUITING

Liverpool Hospital

Sydney, 2170, Australia

RECRUITING

Medizinische Universitaet Wien

Vienna, 1090, Austria

RECRUITING

C.H.U. Brugmann

Brussels, 1020, Belgium

RECRUITING

Universitair Ziekenhuis Leuven

Leuven, 3000, Belgium

RECRUITING

Universidade Federal De Minas Gerais

Belo Horizonte, 30130100, Brazil

RECRUITING

Empresa Brasileira de Servicos Hospitalares EBSERH Hospital das Clinicas da UFG

Goiânia, 74605-050, Brazil

RECRUITING

Instituto de Medicina Integral Professor Fernando Figueira

Recife, 50070902, Brazil

RECRUITING

Instituto D Or de Pesquisa e Ensino IDOR

Rio de Janeiro, 22281 100, Brazil

RECRUITING

Hospital Das Clinicas Da Faculdade De Medicina Da USP

São Paulo, 05403-010, Brazil

RECRUITING

BC Women's Hospital University of British Columbia

Vancouver, British Columbia, V6H 3N1, Canada

RECRUITING

Centre Hospitalier Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

RECRUITING

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Hospices Civils de Lyon - Groupement Hospitalier Est - Hopital Femme Mere Enfant

Bron, 69500, France

RECRUITING

CHRU Lille

Lille, 59000, France

RECRUITING

Hopital Armand Trousseau

Paris, 75012, France

RECRUITING

Charite Universitaetsmedizin Berlin

Berlin, 10117, Germany

RECRUITING

Universitaetsklinikum Giessen und Marburg Standort Giessen

Giessen, 35392, Germany

RECRUITING

Universitaetsklinikum Hamburg Eppendorf

Hamburg, 20251, Germany

RECRUITING

Rotunda Hospital

Dublin, D01 P5W9, Ireland

RECRUITING

Hadassah mount scopus

Jerusalem, 91240, Israel

RECRUITING

Rabin Medical Center

Petah Tikva, 49100, Israel

RECRUITING

The Chaim Sheba Medical Center

Ramat Gan, 5265601, Israel

RECRUITING

Fondazione Policlinico Universitario A Gemelli IRCCS

Roma, 00168, Italy

RECRUITING

Kyushu University Hospital

Fukuoka, 812 8582, Japan

RECRUITING

Gifu Prefectural General Medical Center

Gifu, 500-8717, Japan

RECRUITING

Osaka Women's and Children's Hospital

Izumi-shi, 594-1101, Japan

RECRUITING

Toho University Medical Center Omori Hospital

Ōta-ku, 143-8541, Japan

RECRUITING

Miyagi Children's Hospital

Sendai, 989-3126, Japan

COMPLETED

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

RECRUITING

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

RECRUITING

Hosp. Univ. La Paz

Madrid, 28046, Spain

RECRUITING

Hosp. Virgen Del Rocio

Seville, 41013, Spain

RECRUITING

Karolinska Universitetssjukhuset Huddinge

Stockholm, 14186, Sweden

RECRUITING

Birmingham Women's Hospital

Birmingham, B15 2TG, United Kingdom

RECRUITING

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom

RECRUITING

Kings College Hospital

London, SE5 9RS, United Kingdom

RECRUITING

St Georges Hospital

London, SW17 0QT, United Kingdom

RECRUITING

St.Mary's Hospital

Manchester, M13 9WL, United Kingdom

RECRUITING

John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

RECRUITING

Related Publications (1)

• 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 DERIVED

Related Links

• Azalea Study Website (for the United States only)
• Participant Recruitment Poster

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Central Study Contacts

Study Contact

CONTACT

844-434-4210; Participate-In-This-Study1@its.jnj.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The participants will be randomized in a 2:1 to receive nipocalimab and placebo treatment.

Study Record Dates

• First Submitted: June 13, 2023
• First Posted: June 22, 2023
• Study Start: December 20, 2023
• Primary Completion (Estimated): August 5, 2027
• Study Completion (Estimated): October 8, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

BE (2); US (18); FR (3); NL (1); BR (5); IL (3); AR (2); IE (1); JP (5); AU (1); IT (1); SE (1); DE (3); GB (6); CA (3); ES (3)