A Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of M281 Administered to Pregnant Women at High Risk for Early Onset Severe Hemolytic Disease of the Fetus and Newborn (HDFN)

NCT ID: NCT03842189

Last Updated: 2026-01-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-05

Study Completion Date

2024-08-05

Brief Summary

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The purpose of this study is to evaluate the safety in mother and neonate/infant of M281 administered to pregnant women who are at high risk for Early Onset Severe Hemolytic Disease of the Fetus and Newborn (EOS-HDFN). The effectiveness of the investigational drug M281 will be measured by looking at the percentage of participants with live birth at or after gestational age (GA) 32 weeks and without a need for an intrauterine transfusion (IUT) throughout their entire pregnancy.

Detailed Description

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Conditions

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Hemolytic Disease of the Fetus and Newborn

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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M281

Group Type EXPERIMENTAL

M281

Intervention Type DRUG

Participants will receive once weekly intravenous (IV) infusions of M281

Interventions

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M281

Participants will receive once weekly intravenous (IV) infusions of M281

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Approximately 15 eligible participants and their offspring will be enrolled
* Each participant must meet all of the following criteria to be enrolled in the study:
* Female and greater than or equal to (\>=)18 years of age
* Pregnant to an estimated gestational age of between 8 up to 14 weeks
* A previous pregnancy with a gestation that included at least one of the following prior to week 24 gestation:
* Severe fetal anemia, defined as hemoglobin less than or equal to (\<=) 0.55 multiples of the median (MOM) for gestational age
* Fetal hydrops with peak systolic velocity MOM \>=1.5
* Stillbirth with fetal or placental pathology indicative of hemolytic disease of the fetus and newborn (HDFN)
* Maternal alloantibody titers for anti-D of \>=32, or anti-Kell titers \>=4
* Free fetal deoxyribonucleic acid consistent with an antigen-positive fetus (blood sample taken from mother)
* Maternal evidence for Immunity to measles mumps, rubella, and varicella, as documented by serologies performed during Screening. If initial serologies are borderline or negative, they may be repeated at a second lab. Alternatively, vaccination records can be used to support evidence of immunity.
* Screening immunoglobulin G and albumin levels within the laboratory normal range for gestational age of pregnancy
* Willing to receive standard of care with intrauterine transfusion if clinically indicated
* Agree to receive recommended vaccinations per local standard of care for both mother and child throughout the course of the study
* It is recommended that patients are up-to-date on age-appropriate vaccinations prior to screening as per routine local medical guidelines. For study patients who received locally-approved (and including emergency use-authorized) Coronavirus Disease 2019 (COVID-19) vaccines recently prior to study entry, follow applicable local vaccine labelling, guidelines, and standard of care for pregnant women receiving immune-targeted therapy when determining an appropriate interval between vaccination and study enrollment

Exclusion Criteria

* Currently pregnant with multiples (twins or more)
* Pre-eclampsia In current pregnancy or history of pre-eclampsia in a previous pregnancy
* Gestational hypertension in the current pregnancy
* Current unstable hypertension
* History of severe or recurrent pyelonephritis, 4 or more lower urinary tract infections in the past year or in a previous pregnancy
* History of genital herpes infection
* Active Infection at Screening or Baseline with Coxsackie, syphilis, cytomegalovirus, toxoplasmosis or herpes simplex 1 or 2, as evidenced by clinical signs and symptoms (evidence for prior Infection or exposure, but without clinical signs and symptoms of active infection is acceptable)
* Active infection with tuberculosis as evidenced by positive QuantiFERON-tuberculosis testing
* Requires treatment with corticosteroids or immunosuppression for disorders unrelated to the pregnancy (use of low-potency topical corticosteroids or intra-articular corticosteroids is permitted)
* Has received or is expected to receive any live virus or bacterial vaccine within 12 weeks prior to screening or has a known need to receive a live vaccine while receiving nipocalimab, or within 12 weeks after the last administration of nipocalimab in the study or has received Bacille Calmett-Guérin (BCG) vaccine within 1 year prior to the first administration of nipocalimab
* Currently receiving an antibody-based drug or an Fc-fusion protein drug
* Received plasmapheresis and/or intravenous immunoglobulin during the current pregnancy for treatment of HDFN
* COVID-19 infection: during the 6 weeks prior to baseline (regardless of vaccination status), have had any of: a) confirmed severe acute respiratory syndrome coronavirus(-2) (SARS-CoV-2) (COVID-19) infection (test positive), or; b) suspected SARS-CoV-2 infection (clinical features without documented test results), or; c) close contact with a person with known or suspected SARS-CoV-2 infection. Exception: may be included with a documented negative result for a validated SARSCoV-2 test: obtained at least 2 weeks after conditions a), b), c) above (timed from resolution of key clinical features if present, example fever, cough, dyspnea) and; with absence of all conditions a), b), c) above during the period between the negative test result and the baseline study visit
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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University of California San Francisco

San Francisco, California, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Site Status

University of Texas Health Science Center

Houston, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Liverpool Hospital

Sydney, , Australia

Site Status

Universitair Ziekenhuis Leuven

Leuven, , Belgium

Site Status

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status

Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status

CHUM - Centre hospitalier universitaire de Montreal

Montreal, Quebec, Canada

Site Status

Justus-Liebig-Universität Gießen, Kinderherzzentrum

Giessen, , Germany

Site Status

Leiden University Medical Center

Leiden, , Netherlands

Site Status

Hosp. Univ. San Cecilio

Granada, , Spain

Site Status

Karolinska Universitetssjukhuset Huddinge

Stockholm, , Sweden

Site Status

Birmingham Children's Hospital

Birmingham, , United Kingdom

Site Status

University College London Hospitals NHSFT

London, , United Kingdom

Site Status

Countries

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United States Australia Belgium Canada Germany Netherlands Spain Sweden United Kingdom

References

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de Winter DP, Moise KJ, Ling LE, Oepkes D, Tiblad E, Joanne Verweij EJT, Smoleniec J, Sachs UJ, Bein G, Kilby MD, Miller RS, Devlieger R, Streisand JB, Bredius RGM, Cafone J, Lam E, Leu JH, Mirza A, Nelson RM, Smith V, Schwartz LB, Tjoa ML, Saeed-Khawaja S, Komatsu Y, Lopriore E. Infant Immunity after Maternal Nipocalimab in Severe Hemolytic Disease of the Fetus and Newborn. NEJM Evid. 2026 Feb;5(2):EVIDoa2500097. doi: 10.1056/EVIDoa2500097. Epub 2026 Jan 27.

Reference Type DERIVED
PMID: 41591368 (View on PubMed)

Moise KJ Jr, Ling LE, Oepkes D, Tiblad E, Verweij EJTJ, Lopriore E, Smoleniec J, Sachs UJ, Bein G, Kilby MD, Miller RS, Devlieger R, Audibert F, Emery SP, Markham K, Norton ME, Ocon-Hernandez O, Pandya P, Pereira L, Silver RM, Windrim R, Streisand JB, Leu JH, Mirza A, Smith V, Schwartz LB, Tjoa ML, Saeed-Khawaja S, Komatsu Y, Bussel JB; UNITY Study Group. Nipocalimab in Early-Onset Severe Hemolytic Disease of the Fetus and Newborn. N Engl J Med. 2024 Aug 8;391(6):526-537. doi: 10.1056/NEJMoa2314466.

Reference Type DERIVED
PMID: 39115062 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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MOM-M281-003

Identifier Type: OTHER

Identifier Source: secondary_id

2017-004958-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108980

Identifier Type: -

Identifier Source: org_study_id

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