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)

Phase 2

Completed

• Conditions: Hemolytic Disease of the Fetus and Newborn
• Interventions: Drug: M281

• Registration Number: NCT03842189
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

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

Not available

Study Timeline

• Study Start: 2018-04-05
• Study First Submitted: 2019-02-07
• Study First Submitted QC: 2019-02-12
• Study First Posted: 2019-02-15
• Primary Completion: 2024-08-05
• Study Completion: 2024-08-05
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-08
• Last Update Posted: 2025-01-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 14

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
M281	M281	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs)	From signing of informed consent up to approximately 24 weeks post-delivery for mothers; up to approximately 96 weeks post birth for neonates
Number of Participants With Live Birth at or After Gestational Age (GA) Week 32 and no Intrauterine Transfusion (IUT) Throughout Their Entire Pregnancy	Up to approximately GA Week 37

Secondary Outcome Measures

Name	Time	Method
Number of Participants With live Birth	Up to approximately GA Week 37
Number of Participants at GA Week 24 Without an IUT	GA Week 24
Number of Neonates Requiring Phototherapy	Up to approximately 24 weeks post birth
Number of Simple Transfusions Required by Neonate in the First 12 weeks of Life	Up to 12 weeks post birth
Mean Concentration of M281 in Maternal Participants	GA Week 14 to approximately GA Week 36
Number of Neonates Requiring Exchange transfusions	Up to approximately 24 weeks post birth
Number of Neonates Requiring Simple Transfusions in the First 12 weeks of Life	Up to 12 weeks post birth
Maternal Levels of Total Immunoglobulin G (IgG)	GA Week 14 to approximately GA Week 36
Number of Participants With Fetal Hydrops	Up to approximately 24 weeks post birth	Fetal hydrops is severe edema in the skin and serous cavities of the neonate.
Percentage of Maternal Fc Receptor (FcRn) Receptor Occupancy (RO)	GA Week 14 to approximately GA Week 36
Maternal Levels of Alloantibodies	GA Week 14 to approximately GA Week 36
Gestational age at Delivery	Up to approximately GA Week 37
Number of IUTs Required	Up to approximately GA Week 37
Number of Days of Postnatal Phototherapy Required by Neonate	Up to approximately 24 weeks post birth
Gestational age at First IUT	Up to approximately GA Week 37

Trial Locations

Locations (19)

University of Texas Health Science Center; 🇺🇸 Houston, Texas, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Liverpool Hospital; 🇦🇺 Sydney, Australia

Birmingham Children's Hospital; 🇬🇧 Birmingham, United Kingdom

Hosp. Univ. San Cecilio; 🇪🇸 Granada, Spain

Karolinska Universitetssjukhuset, Huddinge; 🇸🇪 Stockholm, Sweden

University College London Hospitals NHSFT; 🇬🇧 London, United Kingdom

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

British Columbia Children's Hospital; 🇨🇦 Vancouver, British Columbia, Canada

CHUM - Centre hospitalier universitaire de Montreal; 🇨🇦 Montréal, Quebec, Canada

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Universitair Ziekenhuis Leuven; 🇧🇪 Leuven, Belgium

Mount Sinai Hospital; 🇨🇦 Toronto, Ontario, Canada

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Justus-Liebig-Universität Gießen, Kinderherzzentrum; 🇩🇪 Giessen, Germany

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

Dell Children's Medical Center of Central Texas; 🇺🇸 Austin, Texas, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States