Complement Regulation to Undo Systemic Harm in Preeclampsia
Condition: Preeclampsia; Severe Preeclampsia; Eculizumab; HELLP; HELLP Syndrome; HELLP Syndrome Second Trimester; Pregnancy Related; AHUS; PNH; Complement Regulatory Factor Defect; Complement Abnormality; HELLP Syndrome Third Trimester
MeSH terms: Pre-Eclampsia; HELLP Syndrome; Syndrome
Intervention: Eculizumab
Intervention description: Eculizumab Intravenous Solution
Intervention MeSH terms: Eculizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Single arm open label study.
Masking: None (Open Label)
Enrollment: 2.0
Sex: Female
Minimum age: 13 Years
Healthy volunteers: No

Summary:

      This is a Phase II, single arm, open-label study to determine if treatment with eculizumab
      prolongs pregnancy compared to historical controls in women with preeclampsia between 23-30
      weeks gestation.
    

Eligibility criteria:

        Inclusion criteria:

          1. Provision of signed and dated informed consent form

          2. Stated willingness to comply with all study procedures & availability for study
             duration

          3. Biologically female, aged ≥13, body weight ≥40kg

          4. Diagnosed with preeclampsia between 23-29+6/7 weeks gestation, by following criteria:

               1. Blood pressure ≥160 mmHg systolic or ≥110 mmHg diastolic OR

               2. Blood pressure ≥140 mmHg systolic or ≥90 mmHg diastolic and at least one of the
                  following

             i. Proteinuria (spot protein/creatinine ≥0.3mg/mg or 24Hr protein ≥300 mg) ii.
             Platelet count <100,000/μl iii. Aspartate or alanine transaminase >2x upper limit of
             normal iv. Creatinine >1.1 mg/dl or oliguria v. Pulmonary edema

          5. Ability to take intravenous medication and be willing to adhere to the eculizumab
             regimen

          6. Ability to receive meningococcal vaccine and be willing to adhere to antibiotic
             regimen

        Exclusion Criteria:

        An individual who meets any of the following criteria prior to enrollment will be excluded
        from participation in this study:

          1. Known allergic reactions eculizumab or meningococcal vaccine

          2. Febrile illness within prior 2 weeks

          3. Treatment with another investigational drug within previous 6 months

          4. Inpatient expectant management for preeclampsia >72 hours prior to enrollment

          5. Fetal contraindication to expectant management of pregnancy

          6. Platelet count <50,000/μl

          7. Diagnosis of hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome

               -  Must meet all of the following criteria to be excluded: LDH >600 U/L, platelet
                  count < 100,000/μl, AST >2x upper limit of normal, ALT >2x upper limit of normal

          8. Diagnosis of Eclampsia

          9. Diagnosis of Placental abruption

         10. Intrauterine fetal demise

         11. Coagulopathy (INR ≥ 1.5)

         12. Fibrinogen <200 mg/dl

         13. Persistent, severe headache unresponsive to medications

         14. Persistent, severe visual disturbances

         15. Persistent, severe epigastric or RUQ pain unresponsive to medications

         16. Diagnosis of Systemic lupus erythematosus

         17. Diagnosis of Anti-phospholipid antibody syndrome

         18. Diagnosis of Atypical hemolytic uremic syndrome

         19. Diagnosis of Paroxysmal nocturnal hemoglobinuria

         20. Known complement deficiency

         21. Diagnosis of Venous thromboembolism active or within 6 months of enrollment

         22. Diagnosis of Human immunodeficiency virus (HIV)

         23. Diagnosis of Hepatitis C virus (active viremia)

         24. Diagnosis of Cancer (not in remission)

         25. History of Solid organ transplant

         26. Systemic viral or bacterial infection (active, untreated)

         27. Active use of eculizumab at time of enrollment

         28. Contraindication to eculizumab treatment or complement system blockade

         29. Contraindication to meningococcal vaccine

         30. Body weight <40kg

         31. Age <13

         32. Neutropenia (<1500/mm3)

         33. Gonorrhea, chlamydia, or syphilis in current pregnancy

         34. Illicit substance use in current pregnancy

         35. Currently homeless or incarcerated

         36. Alcoholism

         37. Liver cirrhosis

         38. Insulin dependent diabetes

         39. Active use of immunosuppressive therapies, other than use of corticosteroids for fetal
             lung maturity

         40. Use of prophylactic or therapeutic heparin, or low molecular weight heparin, in
             pregnancy for hypercoagulable condition