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)
- Conditions
- fetal blood-disorder100381581000533010000211
- Registration Number
- NL-OMON52622
- Lead Sponsor
- Janssen-Cilag International, NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 1
Each patient must meet all of the following criteria to be enrolled in the
study:
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 (see table in Protocol v6.0 18Dec2019, page 55).
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.
14. 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) COVID-19 vaccines recently prior to study
entry, follow applicable local vaccine labelling, guidelines, and standards
of care for pregnant women receiving immune-targeted therapy when
determining an appropriate interval between vaccination and study
enrollment.
Exclusion Criteria:
Patients who meet any of the following criteria will be excluded from the study:
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 pregnancy, or genital herpes.
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 human immunodeficiency virus (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 patient.
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. 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.
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method