Severe Preeclampsia MedDRA version: 20.0 Level: LLT Classification code 10040444 Term: Severe pre-eclampsia System Organ Class: 100000004868
Conditions
Interventions
Trade Name: DigiFab [Digoxine Immune Fab (Ovine)]
Product Name: AMAG-423
Product Code: AMAG-423
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: DIGOXIN IMMUNE FAB (OVINE)
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Sponsors
AMAG Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has a fetal gestational age of 23 0/7 to 31 6/7 weeks. Gestational age should be confirmed by best obstetrical estimate using one of the following three options: • Confirmed last menstrual period (LMP) and confirmatory ultrasound • Ultrasound alone when LMP is not known or reliable • Known date of conception in instances of assisted reproductive technology 2. At least 18 years of age or older 3. Will be treated with expectant management 4. Singleton gestation 5. Meets modified ACOG (2013) criteria for either preeclampsia or chronic hypertension with superimposed preeclampsia, as specified below: Preeclampsia as defined by: a. Blood pressure greater than or equal to 140 mmHg systolic or greater than or equal to 90 mmHg diastolic on two occasions at least 4 hours apart after 20 weeks of gestation in a woman with a previously normal blood pressure; OR b. Blood pressure greater than or equal to 160 mmHg systolic or greater than or equal to 110 mmHg diastolic, hypertension can be confirmed within a short interval (minutes) to facilitate timely antihypertensive therapy; AND I. Proteinuria: 1. Greater than or equal to 300 mg per 24-hour urine collection (or this amount extrapolated from a timed collection); OR 2. Protein/creatinine ratio greater than or equal to 0.3 (each measured as mg/dL) 3. Dipstick reading of 3+ (used only if more quantitative methods not available) OR in the absence of proteinuria, hypertension with the new onset of any of the following: ii. Thrombocytopenia – platelet count less than 100,000/microliter iii. Renal insufficiency – serum creatinine concentrations greater than 1.1 mg/dL or a doubling of the serum creatinine concentration in the absence of other renal disease iv. Impaired liver function as indicated by abnormally elevated blood concentrations of liver enzymes (two times upper limit of normal for local lab) Chronic hypertension with superimposed preeclampsia as defined by: a. A sudden increase in previously well controlled hypertension or escalation of antihypertensive medications; OR b. New onset proteinuria or a sudden increase in proteinuria in a woman with known proteinuria before or early in pregnancy. 6. Meets modified ACOG (2013) criteria for either preeclampsia with severe features or chronic hypertension with superimposed preeclampsia with severe features, as specified below: Preeclampsia with severe features as defined by at least one of the below: a. Systolic blood pressure of 160 mmHg or higher, or diastolic blood pressure of 110 mmHg or higher on two occasions at least 4 hours apart (unless antihypertensive therapy is initiated before this time) b. Thrombocytopenia – platelet count less than 100,000/microliter c. Impaired liver function as indicated by abnormally elevated blood concentrations of liver enzymes (two times upper limit of normal for local lab) d. Progressive renal insufficiency as defined by serum creatinine concentrations greater than 1.1 mg/dL or a doubling of the serum creatinine concentration in the absence of other renal disease Chronic hypertension with superimposed preeclampsia with severe features as defined by at least one of the below: a. Systolic blood pressure of 160 mmHg or higher, or diastolic blood pressure of 110 mmHg or higher despite escalation of antihypertensive therapy b. Thrombocytopenia – platelet count less than 100,000/microliter c. Impaired liver function as indicated by abnormally elevated blood concentrations of liver enzymes (two times upper
Exclusion criteria
Exclusion criteria: 1. Prior to randomization, the decision to induce or deliver the subject within 24 hours has been made 2. Weight > 150 kg 3. Eclampsia 4. Significant antecedent obstetrical problems which may, in the opinion of the investigator, interfere with study assessments or safe participation in the study 5. Evidence of non-reassuring fetal well-being 6. Evidence of clinically significant fetal anomaly or known chromosomal abnormality 7. Chronic renal disease 8. Active hepatic disease, antiphospholipid antibody syndrome, or lupus 9. Medical or psychiatric disorder which is unstable or which might, in the opinion of the investigator, interfere with study assessments or safe participation in the study 10. Evidence on medical history/evaluation of use of or need for digitalis-like products currently or in the future (e.g., diagnosis of atrial fibrillation) 11. History of an anaphylactic allergic reaction to previous medication, atopy, or allergic reactions to pineapple enzyme bromelain, papain, chymopapain, or other papaya extracts. (Potential subjects with this history may be more susceptible to allergic reactions to DIF). 12. Prior use of antibodies/Fab fragments from sheep (e.g. Digibind®, DigiFab®, CroFab®) 13. Serum creatinine = 2.0 mg/dL 14. Platelet count < 50,000/µL 15. Pulmonary edema requiring treatment with a diuretic 16. Estimated fetal weight < 5th percentile 17. Any investigational drug use within 30 days of screen 18. Planned interventional clinical study participation for infants 19. Current history of methamphetamine or cocaine abuse
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of AMAG-423 for the prevention of intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), or death in the offspring of women with severe preeclampsia.;Secondary Objective: 1. To determine the safety of AMAG-423 in women with severe preeclampsia. 2. To determine the safety of AMAG-423 in the offspring of women with severe preeclampsia. 3. To determine the pharmacokinetics (PK) of AMAG-423 in women with severe preeclampsia.;Primary end point(s): Composite of the incidence of IVH (Grade = 3) or NEC or death in infants from randomization to 36 weeks (± 1 week) corrected gestational age.;Timepoint(s) of evaluation of this end point: Timepoint of primary end point evaluation is from time of randomization until max 37 weeks corrected gestational age for infants | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from baseline in serum creatinine. • Incidence of pulmonary edema during the treatment period.;Timepoint(s) of evaluation of this end point: Secondary end points: 1. 24 hours post-initiation of treatment 2.Treatment period is max 90 hours (~4 days) | — |
Countries
Australia, Colombia, Czech Republic, Hungary, Mexico, Poland, Puerto Rico, South Africa, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactMedical Information
AMAG Pharmaceuticals, Inc.
Outcome results
None listed