The Use of Eculizumab in HELLP Syndrome

Preeclampsia Severe Clinical Trial

Official title:

Eculizumab in HELLP Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04103489
• Other study ID #: IRB00193549
• Secondary ID: 1K12HD085845-01
• Status: Completed
• Phase: Phase 1
• Start date: February 23, 2021
• Est. completion date: September 4, 2023

Study information

• Verified date: November 2023
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research study is being performed to see if women diagnosed with early preterm Hemolysis, Elevated Liver Enzymes, Low Platelets (HELLP) syndrome (estimated gestational ages of 23-30 weeks) benefit from a medication called eculizumab (ECU). This drug blocks a part of the immune system called complement. By blocking this part of the immune system, eculizumab may stop or reverse the progression of the HELLP syndrome disease. The investigators will also look to see if this drug is effective and benefits both the mother and fetus.

Description:

Preeclampsia is a devastating multisystem disorder of pregnancy that manifests as hypertension with or without proteinuria and/or end organ damage caused by endothelial dysfunction and occurs in 3-5% of all pregnancies. Notably, preeclampsia accounts for 30% of all preterm deliveries, which results in neonatal intensive care unit admissions, increased health care cost, severe neonatal morbidity, and neonatal mortality. HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome is the most severe variant of this disorder, and affects approximately 0.1-0.2% of all pregnancies. Despite its prevalence, the cellular biology of HELLP syndrome is unclear resulting in supportive treatment regimens like fetal monitoring, steroids for fetal lung maturity, magnesium for seizure prophylaxis, management of hypertension and ultimately delivery that results in iatrogenic preterm birth. Complement is an enzymatic cascade of approximately 50 proteins which are activated by the classic pathway of complement, the lectin pathway of complement, and the alternative pathway of complement (APC). While the classic pathway depends on antigen-antibody complexes (i.e., lupus) for activation, the APC is antibody independent and has various triggers including infection, trauma, and pregnancy. The investigators' research lab created a novel functional assay, the modified Ham (mHam) assay, to diagnose highly morbid diseases of the APC such atypical hemolytic uremic syndrome (aHUS). Because of the phenotypic similarities of aHUS and HELLP syndrome the investigators' lab undertook a study to test women diagnosed with complete (classic) HELLP and partial (atypical) HELLP syndrome established by Tennessee and American College of Obstetrics and Gynecology (ACOG) criteria to observe if there was dysregulation and overactivation of the APC. The investigators found that most women with HELLP syndrome have APC upregulation; furthermore, it could be inhibited in vitro with anti-C5 monoclonal antibody. In addition, the investigators recently showed approximately 50% of women with HELLP syndrome have germline mutations associated with regulatory proteins of the APC 12. These are the same mutations associated with aHUS; further, 4 of the 5 women with germline mutations are positive by the mHam assay correlating genotype to phenotype. With the investigators' current data that HELLP syndrome is similar to aHUS, the investigators propose an open label clinical trial of ECU administration to women with HELLP syndrome at 23-30 weeks gestation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3
• Est. completion date: September 4, 2023
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Pregnant women diagnosed with HELLP syndrome less than 30 weeks gestation. Exclusion Criteria: Women with
• Disseminated intravascular coagulopathy
• Non-reassuring fetal status necessitating delivery
• Non-viable fetuses
• Stroke
• Fetal demise intra-utero
• Eclamptic seizure
• Known atypical hemolytic uremic syndrome
• Familial or acquired thrombocytopenia purpura
• Paroxysmal nocturnal hemoglobinuria
• Allergy to eculizumab will be excluded.

Related Conditions & MeSH terms

• Complement Abnormality
• HELLP Syndrome
• HELLP Syndrome (HELLP), Third Trimester
• Maternal Injury
• Morbidity;Newborn
• Pre-Eclampsia
• Preeclampsia Severe
• Syndrome

Intervention

Drug:
• Eculizumab
Participants will receive eculizumab at diagnosis of HELLP syndrome. Participants will receive a maximum of 4 doses.

Locations

Country	Name	City	State
United States	The Johns Hopkins University	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in aspartate aminotransferase (AST) level	AST measured in units/L.	Baseline, 72 hours
Primary	Change in alanine aminotransferase (ALT)	ALT measured in IU/L.	Baseline, 72 hours
Primary	Change in lactate dehydrogenase levels (LDH)	LDH measured in units/L.	Baseline, 72 hours
Secondary	Latency of pregnancy	Latency of pregnancy measured in days after eculizumab administration	Up to 7 days
Secondary	Maternal number of units of blood products transfused	Blood products (packed red blood cells, fresh frozen plasma, platelets, cryoprecipitate) measured in units.	Up to 7 days
Secondary	Maternal postpartum length of stay	Postpartum length of stay, measured from delivery to time of discharge in days.	Up to 36 days