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)

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hemolytic Disease of the Fetus and Newborn
• Intervention / Treatment: Drug: M281

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Expanded Access

Temporarily not available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • Sydney, Australia, 2170
    • Liverpool Hospital
• Belgium
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3N1
      • British Columbia Children's Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • CHUM - Centre hospitalier universitaire de Montreal
• Germany
  • Giessen, Germany, 35392
    • Justus-Liebig-Universität Gießen, Kinderherzzentrum
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center
• Spain
  • Granada, Spain, 18016
    • Hosp. Univ. San Cecilio
• Sweden
  • Stockholm, Sweden, SE-141 86
    • Karolinska Universitetssjukhuset, Huddinge
• United Kingdom
  • Birmingham, United Kingdom, B15 2TG
    • Birmingham Children's Hospital
  • London, United Kingdom, WC1E 6DB
    • University College London Hospitals NHSFT
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center of Central Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: M281	Drug: M281; Participants will receive once weekly intravenous (IV) infusions of M281

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
Number of IUTs Required		Up to approximately GA Week 37
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
Gestational age at First IUT		Up to approximately GA Week 37
Gestational age at Delivery		Up to approximately GA Week 37
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
Number of Neonates Requiring Phototherapy		Up to approximately 24 weeks post birth
Number of Neonates Requiring Exchange transfusions		Up to approximately 24 weeks post birth
Number of Days of Postnatal Phototherapy Required by Neonate		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
Number of Simple Transfusions Required by Neonate in the First 12 weeks of Life		Up to 12 weeks post birth
Percentage of Maternal Fc Receptor (FcRn) Receptor Occupancy (RO)		GA Week 14 to approximately GA Week 36
Maternal Levels of Total Immunoglobulin G (IgG)		GA Week 14 to approximately GA Week 36
Maternal Levels of Alloantibodies		GA Week 14 to approximately GA Week 36
Mean Concentration of M281 in Maternal Participants		GA Week 14 to approximately GA Week 36

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2018
• Primary Completion (Estimated): October 4, 2024
• Study Completion (Estimated): November 8, 2024

Study Registration Dates

• First Submitted: February 7, 2019
• First Submitted That Met QC Criteria: February 12, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Alloimmunization; Pregnant women; HDFN; Isoimmunization; M281; Hemolytic Disease of the Fetus and Newborn; Rhesus Disease; Hemolytic disease due to fetomaternal alloimmunization; Hemolytic disease of the newborn with Kell alloimmunization; Rhesus (Rh) isoimmunization of foetus or newborn; Isoimmunization due to other red cell factors; ABO isoimmunization of foetus or newborn; Haemolytic anaemia due to other unclassified antibodies; Isoimmune; Isoimmunized; Alloimmune; Alloimmunized
• Additional Relevant MeSH Terms: Pathologic Processes; Hemolysis
• Other Study ID Numbers: CR108980; 2017-004958-42 (EudraCT Number); MOM-M281-003 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No