Complement Regulation to Undo Systemic Harm in Preeclampsia

NCT04725812 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: STUDY00000039
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Latency (in Days) From Enrollment to Delivery

  The difference in mean number of days (latency) from enrollment in the study (or hospital admission for controls) to delivery between participant receiving eculizumab compared to historical controls. * For treatment-arm participants latency is determined from enrollment to delivery. * For historical controls latency is determined from hospital admission (or initial diagnosis for controls hospitalized for other indication) for preeclampsia until delivery. * Subjects and historical controls all defined as women with preeclampsia between 23-30 weeks gestation.

  24 months

Secondary Outcomes (16)

• Composite Adverse Maternal Outcomes

  24 months

• Composite Adverse Neonatal Outcomes

  24 months

• Changes in Blood and Urine Concentrations of Terminal Complement Protein C5a Before and After Each Treatment.

  24 months

• Changes in Blood and Urine Concentrations of Terminal Complement Protein C5b-9 Before and After Each Treatment.

  24 months

• Changes in Blood and Urine Concentrations of Complement Protein CD59 Before and After Each Treatment.

  24 months

Study Arms (1)

Eculizumab

EXPERIMENTAL

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).

Drug: Eculizumab

Interventions

Eculizumab DRUG

Eculizumab Intravenous Solution

Also known as: Soliris

Eculizumab

Eligibility Criteria

• Age: 13 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures \& availability for study duration
• Biologically female, aged ≥13, body weight ≥40kg
• Diagnosed with preeclampsia between 23-29+6/7 weeks gestation, by following criteria:
• Blood pressure ≥160 mmHg systolic or ≥110 mmHg diastolic OR
• 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
• Ability to take intravenous medication and be willing to adhere to the eculizumab regimen
• Ability to receive meningococcal vaccine and be willing to adhere to antibiotic regimen

You may not qualify if:

• An individual who meets any of the following criteria prior to enrollment will be excluded from participation in this study:
• Known allergic reactions eculizumab or meningococcal vaccine
• Febrile illness within prior 2 weeks
• Treatment with another investigational drug within previous 6 months
• Inpatient expectant management for preeclampsia \>72 hours prior to enrollment
• Fetal contraindication to expectant management of pregnancy
• Platelet count \<50,000/μl
• 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
• Diagnosis of Eclampsia
• Diagnosis of Placental abruption
• Intrauterine fetal demise
• Coagulopathy (INR ≥ 1.5)
• Fibrinogen \<200 mg/dl
• Persistent, severe headache unresponsive to medications

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• Alexion Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Pre-Eclampsia; HELLP Syndrome

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Limitations and Caveats

The PI, Dr. Richard Burwick left the institution where this research was being conducted in April 2022 and study activity halted at that time. Two subjects were consented to participate in the study and one withdrew participation before study procedures were completed. Study Funding was terminated by Sponsor. Dr. Karumanchi is a co-investigator in this study who has been named as the Responsible Party within the PRS system solely for the purpose of reporting the results.

Results Point of Contact

• Title: Professor of Medicine, Cedars-Sinai Medical Center
• Organization: Cedars-Sinai Medical Center

sananth.karumanchi@csmc.edu

310-423-7608

Study Officials

• Richard Burwick, MD, MPH

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Cedars-Sinai Medical Center

Model Details: Single arm open label study.

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: January 27, 2021
• Study Start: September 13, 2021
• Primary Completion: December 7, 2021
• Study Completion: December 7, 2021
• Last Updated: November 29, 2023
• Results First Posted: November 29, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)