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)

Hemolytic Disease of the Fetus and Newborn Clinical Trial

Official title:

A Multicenter, Open-label 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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03842189
• Other study ID #: CR108980
• Secondary ID: 2017-004958-42MO
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 5, 2018
• Est. completion date: November 8, 2024

Study information

• Verified date: May 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 14
• Est. completion date: November 8, 2024
• Est. primary completion date: October 4, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemolysis
• Hemolytic Disease of the Fetus and Newborn

Intervention

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

Locations

Country	Name	City	State
Australia	Liverpool Hospital	Sydney
Belgium	Universitair Ziekenhuis Leuven	Leuven
Canada	CHUM - Centre hospitalier universitaire de Montreal	Montréal	Quebec
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Germany	Justus-Liebig-Universität Gießen, Kinderherzzentrum	Giessen
Netherlands	Leiden University Medical Center	Leiden
Spain	Hosp. Univ. San Cecilio	Granada
Sweden	Karolinska Universitetssjukhuset, Huddinge	Stockholm
United Kingdom	Birmingham Children's Hospital	Birmingham
United Kingdom	University College London Hospitals NHSFT	London
United States	Dell Children's Medical Center of Central Texas	Austin	Texas
United States	University of Cincinnati	Cincinnati	Ohio
United States	University of Texas Health Science Center	Houston	Texas
United States	Columbia University Medical Center	New York	New York
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	University of Utah	Salt Lake City	Utah
United States	University of California San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Germany,  Netherlands,  Spain,  Sweden,  United Kingdom, 

Outcome

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