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The Use of Eculizumab in HELLP Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04103489
Recruitment Status : Not yet recruiting
First Posted : September 25, 2019
Last Update Posted : October 11, 2019
Information provided by (Responsible Party):
Johns Hopkins University

Brief 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.

Condition or disease Intervention/treatment Phase
HELLP Syndrome (HELLP), Third Trimester Complement Abnormality Morbidity;Newborn Maternal Injury Preeclampsia Severe Drug: Eculizumab Phase 1

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This will be an open label, phase 1 clinical trial. The investigators will investigate if eculizumab halts or prevents worsening or HELLP syndrome in women at 23-28 weeks gestation.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Eculizumab in HELLP Syndrome
Estimated Study Start Date : January 1, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : January 4, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Eculizumab

Arm Intervention/treatment
Experimental: HELLP Syndrome at less than 28 weeks gestation
Women diagnosed with HELLP syndrome at 23-30 weeks gestation will receive eculizumab.
Drug: Eculizumab
Participants will receive eculizumab at diagnosis of HELLP syndrome. Participants will receive a maximum of 4 doses.
Other Name: Soliris

Primary Outcome Measures :
  1. Change in aspartate aminotransferase (AST) level [ Time Frame: Baseline, 72 hours ]
    AST measured in units/L.

  2. Change in alanine aminotransferase (ALT) [ Time Frame: Baseline, 72 hours ]
    ALT measured in IU/L.

  3. Change in lactate dehydrogenase levels (LDH) [ Time Frame: Baseline, 72 hours ]
    LDH measured in units/L.

Secondary Outcome Measures :
  1. Latency of pregnancy [ Time Frame: Up to 7 days ]
    Latency of pregnancy measured in days after eculizumab administration

  2. Maternal number of units of blood products transfused [ Time Frame: Up to 7 days ]
    Blood products (packed red blood cells, fresh frozen plasma, platelets, cryoprecipitate) measured in units.

  3. Maternal postpartum length of stay [ Time Frame: Up to 36 days ]
    Postpartum length of stay, measured from delivery to time of discharge in days.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Pregnant women diagnosed with HELLP syndrome less than 28 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04103489

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Contact: Arthur J Vaught 4048496018

Sponsors and Collaborators
Johns Hopkins University
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Principal Investigator: Arthur J Vaught Johns Hopkins University

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Responsible Party: Johns Hopkins University Identifier: NCT04103489    
Other Study ID Numbers: IRB00193549
First Posted: September 25, 2019    Key Record Dates
Last Update Posted: October 11, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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HELLP Syndrome
Pathologic Processes
Hypertension, Pregnancy-Induced
Pregnancy Complications