Complement Regulation to Undo Systemic Harm in Preeclampsia

NCT ID: NCT04725812

Last Updated: 2023-11-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-13
• Study Completion Date: 2021-12-07

Brief 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.

Detailed Description

The purpose of this study is to determine if eculizumab is an effective treatment to prolong pregnancy in women with preeclampsia, compared to a historical control group of women that received standard of care alone. Eligible subjects will be women with preeclampsia before 30 weeks gestation, who have been deemed suitable for prolongation of pregnancy.

The primary research procedure is administration of the study drug, eculizumab, by intravenous infusions weekly for four weeks, then every other week. Eculizumab is approved by the FDA for the treatment of women with atypical hemolytic uremic syndrome and paroxysmal nocturnal hemoglobinuria and is frequently used in pregnant women with these disorders. However, eculizumab is considered investigational in this study because it has not been approved by the FDA for use in patients with preeclampsia. Subject participation will last approximately 8-12 weeks on average, and the study drug will be continued until 48 hours after delivery in the treatment arm. All subjects will be followed at 2 weeks and 6 weeks after delivery to assess maternal and neonatal outcomes. A later visit may be required to complete the meningococcal vaccine schedule.

The investigators believe that eculizumab will prolong pregnancy in women with preeclampsia diagnosed before 30 weeks gestation with overactive complement. As there is no effective treatment for preeclampsia other than delivery currently, women with preeclampsia before 30 weeks gestation are managed using a "watch and wait" approach (i.e., expectant management). Due to the unpredictable nature of preeclampsia, expectant management places mother and child at significant risk until delivery occurs. Eculizumab may be an improvement over current standard of care as it provides a treatment option for patients who would otherwise be managed with expectant management alone. If the study aims are achieved, eculizumab will emerge as an effective treatment option for women with preeclampsia.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Eculizumab

Twelve subjects in the interventional arm will receive eculizumab at an induction dose of 900mg IV weekly (q7 days) for 4 weeks followed by a dose of 1200mg IV at week 5. Thereafter, patients will receive a maintenance dose of 1200mg IV every two weeks (q14 days). The last dose of eculizumab will be given up to 48 hours post-partum, with a dose that is dependent on the dosing schedule (i.e. whether the last dose is given within the 4-week induction period or is during the maintenance phase).

Group Type: EXPERIMENTAL

Eculizumab

Intervention Type: DRUG

Eculizumab Intravenous Solution

Interventions

Eculizumab

Eculizumab Intravenous Solution

Intervention Type: DRUG

Other Intervention Names

Soliris

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

• Minimum Eligible Age: 13 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

S Ananth Karumanchi

Professor of Medicine, Cedars-Sinai Medical Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard Burwick, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

STUDY00000039

Identifier Type: -

Identifier Source: org_study_id