HELLP Syndrome (HELLP), Third TrimesterPhase 1NCT04103489
The Use of Eculizumab in HELLP Syndrome
A Phase 1 study testing Eculizumab in people with HELLP Syndrome (HELLP), Third Trimester and Complement Abnormality, run by Johns Hopkins University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- HELLP Syndrome (HELLP), Third Trimester, Complement Abnormality, Morbidity;Newborn
- What is being tested?
- Eculizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Feb 2021to 4 Sep 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Pregnant women diagnosed with HELLP syndrome less than 30 weeks gestation.
Who cannot join
- Women with
- Disseminated intravascular coagulopathy
- Non-reassuring fetal status necessitating delivery
- Non-viable fetuses
- Stroke
- Fetal demise intra-utero
Show all 11Show fewer
- Eclamptic seizure
- Known atypical hemolytic uremic syndrome
- Familial or acquired thrombocytopenia purpura
- Paroxysmal nocturnal hemoglobinuria
- Allergy to eculizumab will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Johns Hopkins University
Baltimore, Maryland, 21287
About this study
Official title: Eculizumab in HELLP Syndrome
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.
Read the 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.
- Conditions
- HELLP Syndrome (HELLP), Third Trimester, Complement Abnormality, Morbidity;Newborn, Maternal Injury, Preeclampsia Severe
- Being tested
- Eculizumab
- Medical subject headings
- HELLP Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EculizumabDrug
Also called Soliris
Participants will receive eculizumab at diagnosis of HELLP syndrome. Participants will receive a maximum of 4 doses.
| Study group | Role | What they receive |
|---|---|---|
| HELLP Syndrome at less than 30 weeks gestation | Experimental | Women diagnosed with HELLP syndrome at 23-30 weeks gestation will receive eculizumab. Receives: Drug: Eculizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in aspartate aminotransferase (AST) level
AST measured in units/L.
Measured: Baseline, 72 hours
Change in alanine aminotransferase (ALT)
ALT measured in IU/L.
Measured: Baseline, 72 hours
Change in lactate dehydrogenase levels (LDH)
LDH measured in units/L.
Measured: Baseline, 72 hours
Secondary outcomes (3)
Latency of pregnancy
Latency of pregnancy measured in days after eculizumab administration
Measured: Up to 7 days
Maternal number of units of blood products transfused
Blood products (packed red blood cells, fresh frozen plasma, platelets, cryoprecipitate) measured in units.
Measured: Up to 7 days
Maternal postpartum length of stay
Postpartum length of stay, measured from delivery to time of discharge in days.
Measured: Up to 36 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2019
- Study start23 Feb 2021
- Primary completion31 Aug 2023
- Study completion4 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HELLP Syndrome (HELLP), Third TrimesterStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Arthur J Vaught, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04103489
- Sponsor's protocol ID
- IRB00193549
- Other IDs
- 1K12HD085845-01
- Status last verified
- Nov 2023
- First submitted
- 24 Sep 2019
- Last updated
- 14 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Eculizumab in HELLP Syndrome
- ClinicalTrials.gov ID
- NCT04103489
- Acronym / sponsor ID
- IRB00193549
- Conditions
- HELLP Syndrome (HELLP), Third Trimester, Complement Abnormality, Morbidity;Newborn, Maternal Injury, Preeclampsia Severe
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 23 Feb 2021 (actual)
- Primary completion
- 31 Aug 2023 (actual)
- Study completion
- 4 Sep 2023 (actual)
- First posted
- 25 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| HELLP Syndrome at less than 30 weeks gestation | Experimental | Drug: EculizumabWomen diagnosed with HELLP syndrome at 23-30 weeks gestation will receive eculizumab. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Pregnant women diagnosed with HELLP syndrome less than 30 weeks gestation.
Key exclusion criteria (11 listed)
- Women with
- Disseminated intravascular coagulopathy
- Non-reassuring fetal status necessitating delivery
- Non-viable fetuses
- Stroke
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EculizumabAlso: SolirisParticipants will receive eculizumab at diagnosis of HELLP syndrome. Participants will receive a maximum of 4 doses. | Drug | HELLP Syndrome at less than 30 weeks gestation |
Primary outcome
Change in aspartate aminotransferase (AST) level
Time frame: Baseline, 72 hours
AST measured in units/L.
Change in alanine aminotransferase (ALT)
Time frame: Baseline, 72 hours
ALT measured in IU/L.
Change in lactate dehydrogenase levels (LDH)
Time frame: Baseline, 72 hours
LDH measured in units/L.
3 secondary outcomes
Latency of pregnancy
Time frame: Up to 7 days
Maternal number of units of blood products transfused
Time frame: Up to 7 days
Maternal postpartum length of stay
Time frame: Up to 36 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2023.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arthur J Vaught principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Eculizumab in people with HELLP Syndrome (HELLP), Third Trimester and Complement Abnormality, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in aspartate aminotransferase (AST) level (time frame: Baseline, 72 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2023.