Early onset Severe Hemolytic Disease of the fetus and newborn (HDFN) MedDRA version: 20.0 Level: LLT Classification code 10019512 Term: Hemolytic disease due to Rh isoimmunization of fetus or newborn System Organ Class: 100000004850
Conditions
Interventions
Product Name: nipocalimab
Product Code: M281
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: nipocalimab
CAS Number: 2211985-36-1
Current Sponsor code: M281
Concentrati
Sponsors
Momenta Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to understand and voluntarily provide written informed consent to participate in the study. 2. Female and =18 years of age. 3. Pregnant to an estimated GA of 8 up to 14 weeks. 4. A previous pregnancy with a gestation that included at least one of the following at =24 weeks gestation: a. Severe fetal anemia, defined as hemoglobin =0.55 multiples of the median (MoM) for GA **refer to table on page 12 of the protocol. b. Fetal hydrops (ascites) with an MCA-PSV MoM =1.5 c. Stillbirth with fetal or placental pathology indicative of HDFN 5. Maternal alloantibody titers for anti-D of =32, or anti-Kell titers =8. 6. Free fetal deoxyribonucleic acid (DNA) consistent with an antigen positive fetus (blood sample drawn from the mother). 7. 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. 8. Screening IgG and albumin levels within the laboratory normal ranges. 9. Willing to receive standard of care with IUT if clinically indicated. 10. Agree to receive recommended vaccinations per local standard of care for both mother and child throughout the course of the study. 11. Willing to forego collection of cord blood for stem cell storage or other non-study purposes. 12. For mother and neonate, willing to forego participation in another clinical trial of an investigational therapy for the duration of their participation in the current study. 13. Willing to consent to a 24-week safety follow-up period for the patient and a 96-week safety follow-up period for the neonate/infant. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Currently pregnant with multiples (twins or more). 2. Pre-eclampsia in current pregnancy or history of pre-eclampsia in a previous pregnancy. 3. Gestational hypertension in the current pregnancy 4. Current unstable hypertension 5. History of severe or recurrent pyelonephritis; or 4 or more lower urinary tract infections in the past year or in a previous 6. History of genital herpes infection 7. History of atypical mycobacterial disease or herpes zoster infection within the last 6 months. 8. History of malignancy (except treated basal cell carcinoma of the skin) with or without systemic cancer chemotherapy. 9. Positive for HIV, hepatitis B, or hepatitis C during Screening. 10. Presence of any of the following during Screening: clinically significant abnormal hematologic laboratory values, creatinine >1.5 X upper limit normal (ULN), or clinically significant abnormal ECG reflective of heart disease. 11. 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). 12. Active infection with tuberculosis as evidenced by positive QuantiFERON-TB testing. 13. Immunosuppression because of underlying medical condition, including: • History of hereditary or congenital immunodeficiencies, cellular immunodeficiencies, hypogammaglobulinemia, or dysgammaglobulinemia • History of solid organ or bone marrow transplantation • Any prior history of other clinically significant immunosuppressive or clinically diagnosed autoimmune disease that may jeopardize the safety of the subject, require therapy that would interfere with study assessments or endpoint evaluation, or otherwise impact the validity of the study results 14. Requires treatment with corticosteroids or immunosuppression for disorders unrelated to the pregnancy (use of low-potency topical corticosteroids or intra-articular corticosteroids is permitted). 15. History of drug allergy, hypersensitivity, or intolerance to any drug product that, in the opinion of the Investigator, would compromise the safety of the patien 16. In the Investigator's opinion, shows evidence of ongoing alcohol/substance abuse/dependence. 17. Smoking during pregnancy. 18. Received plasmapheresis and/or IVIG during the current pregnancy for treatment of HDFN. 19. Received live vaccine within 3 months prior to receiving the first IV infusion of nipocalimab 20. Currently receiving an antibody-based drug or an Fc-fusion protein drug 21. Received an investigational drug and/or device within 30 days or 5 half-lives prior to receiving the first IV infusion of nipocalimab. 22. Received nipocalimab in a prior clinical trial 23. A history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine/metabolic, immunologic, dermatologic, neurologic, oncologic, psychiatric disease or severe or recurrent infections (eg, frequent hospitalized pneumonia), dermatologic, neurologic, oncologic, or psychiatric disease, or any other condition or issue that, in the opinion of the Investigator, would jeopardize the safety of the patient or fetus/neonate/infant or the validity of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the safety in mother and neonate/infant of nipocalimab administered to pregnant women at high risk for EOS-HDFN. •To evaluate the efficacy of nipocalimab as measured by proportion of patients with live birth at or after gestational age (GA) 32 weeks and without intrauterine transfusion (IUT) throughout their entire pregnancy. ;Secondary Objective: •To evaluate the efficacy of nipocalimab on antenatal management and outcome as measured by GA at first fetal IUT, frequency of fetal IUT, and frequency of live birth. •To evaluate the efficacy of nipocalimab on postnatal management and outcome as measured by severity of hyperbilirubinemia, phototherapy, exchange transfusions, and transfusions in the first 12 weeks of life. •To evaluate the PD activity of nipocalimab as measured by effects on maternal FcRn occupancy, and maternal and neonatal/infant levels of total IgG and alloantibodies. •To evaluate the PK of nipocalimab. ;Primary end point(s): 1) Incidence and severity of AEs, SAEs, and AESIs (i.e., infections requiring use of oral or intravenous anti-infectives in the patient; hypoalbuminemia = Grade 3) 2)Proportion of patients with live birth at or after GA Week 32 and without an IUT throughout their entire pregnancy;Timepoint(s) of evaluation of this end point: 1) continuous throughout the whole trial 2)week 32 and at birth | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Global Clinical Outcome 2) Percentage of patients with live birth 3) Percentage of patients at GA Week 24 without an IUT 4) GA at first IUT 5) Number of IUTs required 6) Gestational age at delivery 7) Percentage of patients with fetal hydrops 8) Percentage of neonates requiring phototherapy 9) Percentage of neonates requiring exchange transfusions 10) Number of days of phototherapy required by neonate 11) Percentage of neonates requiring simple transfusions in the first12 weeks of life 12) Number of simple transfusions required by neonate in the first 12 weeks of life ;Timepoint(s) of evaluation of this end point: 1) at birth 2) at birth 3) at Week GA 24 4) at first IUT 5) at birth 6) at birth 7) after birth 8) within first 12 weeks of birth 9) within first 12 weeks of birth 10) within first 12 weeks of birth 11) within first 12 weeks of birth 12) within first 12 weeks of birth | — |
Countries
Australia, Belgium, Canada, Germany, Israel, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactChelsea Toner
Momenta Pharmaceuticals Inc.
Outcome results
None listed