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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)

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ClinicalTrials.gov Identifier: NCT03842189
Recruitment Status : Recruiting
First Posted : February 15, 2019
Last Update Posted : September 29, 2021
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Hemolytic Disease of the Fetus and Newborn Drug: M281 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : April 2, 2019
Estimated Primary Completion Date : July 31, 2022
Estimated Study Completion Date : April 15, 2024

Arm Intervention/treatment
Experimental: M281 Drug: M281
Participants will receive once weekly intravenous (IV) infusions of M281




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

Secondary Outcome Measures :
  1. Global Clinical Outcome (GCO) Rank Score (GCO Rank) [ Time Frame: Up to approximately GA Week 37; up to approximately 12 weeks post birth ]
  2. Number of Participants With GCO Clinically Meaningful Classification (GCO Class) [ Time Frame: Up to approximately GA Week 37; up to approximately 12 weeks post birth ]
  3. Number of Participants With live Birth [ Time Frame: Up to approximately GA Week 37 ]
  4. Number of Participants at GA Week 24 Without an IUT [ Time Frame: GA Week 24 ]
  5. Gestational age at First IUT [ Time Frame: Up to approximately GA Week 37 ]
  6. Number of IUTs Required [ Time Frame: Up to approximately GA Week 37 ]
  7. Gestational age at Delivery [ Time Frame: Up to approximately GA Week 37 ]
  8. Number of Participants With Fetal Hydrops [ Time Frame: Up to approximately 24 weeks post birth ]
    Fetal hydrops is severe edema in the skin and serous cavities of the neonate.

  9. Number of Neonates Requiring Phototherapy [ Time Frame: Up to approximately 24 weeks post birth ]
  10. Number of Neonates Requiring Exchange transfusions [ Time Frame: Up to approximately 24 weeks post birth ]
  11. Number of Days of Postnatal Phototherapy Required by Neonate [ Time Frame: Up to approximately 24 weeks post birth ]
  12. Number of Neonates Requiring Simple Transfusions in the First 12 weeks of Life [ Time Frame: Up to 12 weeks post birth ]
  13. Number of Simple Transfusions Required by Neonate in the First 12 weeks of Life [ Time Frame: Up to 12 weeks post birth ]
  14. Percentage of Maternal Fc Receptor (FcRn) Receptor Occupancy (RO) [ Time Frame: GA Week 14 to approximately GA Week 36 ]
  15. Maternal Levels of Total Immunoglobulin G (IgG) [ Time Frame: GA Week 14 to approximately GA Week 36 ]
  16. Maternal Levels of Alloantibodies [ Time Frame: GA Week 14 to approximately GA Week 36 ]
  17. Mean Concentration of M281 in Maternal Participants [ Time Frame: GA Week 14 to approximately GA Week 36 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 ≥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 ≤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)
  • MaternaI 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 enrolment

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)
  • Received live vaccine within 3 months prior to first intravenous infusion 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, 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03842189


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Additional Information:
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03842189    
Other Study ID Numbers: CR108980
2017-004958-42 ( EudraCT Number )
MOM-M281-003 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: September 29, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Janssen Research & Development, LLC:
M281
Hemolytic Disease of the Fetus and Newborn
HDFN
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
Isoimmunization
Alloimmune
Alloimmunized
Alloimmunization
Pregnant women
Additional relevant MeSH terms:
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Hemolysis
Pathologic Processes