Clinical trial NCT03842189: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemolytic Disease of the Fetus and Newborn
Keywords: 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
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-02-15
Enrollment: 14
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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 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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From signing of informed consent up to approximately 24 weeks post-delivery for mothers; up to approximately 96 weeks post birth for neonates
measure: Number of Participants With Live Birth at or After Gestational Age (GA) Week 32 and no Intrauterine Transfusion (IUT) Throughout Their Entire Pregnancy
timeFrame: Up to approximately GA Week 37
Secondary outcomes:
measure: Number of Participants With live Birth
timeFrame: Up to approximately GA Week 37
measure: Number of Participants at GA Week 24 Without an IUT
timeFrame: GA Week 24
measure: Gestational age at First IUT
timeFrame: Up to approximately GA Week 37
measure: Number of IUTs Required
timeFrame: Up to approximately GA Week 37
measure: Gestational age at Delivery
timeFrame: Up to approximately GA Week 37
measure: Number of Participants With Fetal Hydrops
timeFrame: Up to approximately 24 weeks post birth
measure: Number of Neonates Requiring Phototherapy
timeFrame: Up to approximately 24 weeks post birth
measure: Number of Neonates Requiring Exchange transfusions
timeFrame: Up to approximately 24 weeks post birth
measure: Number of Days of Postnatal Phototherapy Required by Neonate
timeFrame: Up to approximately 24 weeks post birth
measure: Number of Neonates Requiring Simple Transfusions in the First 12 weeks of Life
timeFrame: Up to 12 weeks post birth
measure: Number of Simple Transfusions Required by Neonate in the First 12 weeks of Life
timeFrame: Up to 12 weeks post birth
measure: Percentage of Maternal Fc Receptor (FcRn) Receptor Occupancy (RO)
timeFrame: GA Week 14 to approximately GA Week 36
measure: Maternal Levels of Total Immunoglobulin G (IgG)
timeFrame: GA Week 14 to approximately GA Week 36
measure: Maternal Levels of Alloantibodies
timeFrame: GA Week 14 to approximately GA Week 36
measure: Mean Concentration of M281 in Maternal Participants
timeFrame: GA Week 14 to approximately GA Week 36
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Sydney
country: Australia
facility: Liverpool Hospital
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montréal
country: Canada
facility: CHUM - Centre hospitalier universitaire de Montreal
state: Quebec
city: Giessen
country: Germany
facility: Justus-Liebig-Universität Gießen, Kinderherzzentrum
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Granada
country: Spain
facility: Hosp. Univ. San Cecilio
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Huddinge
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: London
country: United Kingdom
facility: University College London Hospitals NHSFT
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: