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)

• Status: Recruiting
• Trial end date: 2024-04-15
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Janssen Research & Development, LLC; Momenta Pharmaceuticals, Inc.

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