Complement Regulation to Undo Systemic Harm in Preeclampsia

• Status: Recruiting
• Trial end date: 2024-03-13
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cedars-Sinai Medical Center
• Collaborator: Alexion Pharmaceuticals
• Treatments: Eculizumab

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