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)

• ClinicalTrials.gov Identifier: NCT03842189
• Recruitment Status: Recruiting
• First Posted: February 15, 2019
• Last Update Posted: February 5, 2021
• Sponsor: Momenta Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Momenta Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: February 7, 2019
• First Posted Date: February 15, 2019
• Last Update Posted Date: February 5, 2021
• Actual Study Start Date: June 10, 2019
• Estimated Primary Completion Date: May 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 26, 2019)

• 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 ]
• 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 ]

Original Primary Outcome Measures (submitted: February 12, 2019)

• 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 ]
• Number of Participants With Live Birth at or After Gestational Age (GA) Week 32 and no Intrauterine Transfusion (IUT) throughout the study [ Time Frame: Up to approximately GA Week 37 ]

Current Secondary Outcome Measures (submitted: February 12, 2019)

• Global Clinical Outcome (GCO) Rank Score (GCO Rank) [ Time Frame: Up to approximately GA Week 37; up to approximately 12 weeks post birth ]
• 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 ]
• Number of Participants With live Birth [ Time Frame: Up to approximately GA Week 37 ]
• Number of Participants at GA Week 24 Without an IUT [ Time Frame: GA Week 24 ]
• Gestational age at First IUT [ Time Frame: Up to approximately GA Week 37 ]
• Number of IUTs Required [ Time Frame: Up to approximately GA Week 37 ]
• Gestational age at Delivery [ Time Frame: Up to approximately GA Week 37 ]
• 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.
• Number of Neonates Requiring Phototherapy [ Time Frame: Up to approximately 24 weeks post birth ]
• Number of Neonates Requiring Exchange transfusions [ Time Frame: Up to approximately 24 weeks post birth ]
• Number of Days of Postnatal Phototherapy Required by Neonate [ Time Frame: Up to approximately 24 weeks post birth ]
• Number of Neonates Requiring Simple Transfusions in the First 12 weeks of Life [ Time Frame: Up to 12 weeks post birth ]
• Number of Simple Transfusions Required by Neonate in the First 12 weeks of Life [ Time Frame: Up to 12 weeks post birth ]
• Percentage of Maternal Fc Receptor (FcRn) Receptor Occupancy (RO) [ Time Frame: GA Week 14 to approximately GA Week 36 ]
• Maternal Levels of Total Immunoglobulin G (IgG) [ Time Frame: GA Week 14 to approximately GA Week 36 ]
• Maternal Levels of Alloantibodies [ Time Frame: GA Week 14 to approximately GA Week 36 ]
• Mean Concentration of M281 in Maternal Participants [ Time Frame: GA Week 14 to approximately GA Week 36 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hemolytic Disease of the Fetus and Newborn

Intervention

Drug: M281

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

Study Arms

Experimental: M281

Intervention: Drug: M281

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 12, 2019): 15
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2022
• Estimated Primary Completion Date: May 31, 2021 (Final data collection date for primary outcome measure)

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 ≥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

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Momenta General Queries; +1 617-491-9700; ClinicalTrialInfo@momentapharma.com

• Listed Location Countries: Australia, Belgium, Canada, Germany, Netherlands, Spain, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT03842189
• Other Study ID Numbers: MOM-M281-003; 2017-004958-42 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Momenta Pharmaceuticals, Inc.
• Study Sponsor: Momenta Pharmaceuticals, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Momenta General Queries; Momenta Pharmaceuticals, Inc.

• PRS Account: Momenta Pharmaceuticals, Inc.
• Verification Date: January 2021