Ravulizumab for Severe Preeclampsia

Overseen By Gonzalez Suarez

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Disqualifiers: DIC, Stroke, Thrombocytopenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

14 Participants Needed

Trial Summary

What is the purpose of this trial?

The researchers are testing a medication named ravulizumab for the treatment of severe preeclampsia and Hemolysis, Elevated Liver enzymes, Low Platelets (HELLP) syndrome.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is Ravulizumab safe for use in humans?

Ravulizumab, also known as Ultomiris or ALXN1210, has been studied for safety in humans for other conditions, such as paroxysmal nocturnal hemoglobinuria (a rare blood disorder) and atypical hemolytic uremic syndrome (a disease that affects blood and blood vessels). These studies generally show that it is safe for human use, with common side effects including headache, fever, and nausea. ^{1 2 3 4 5}

How is the drug Ravulizumab different from other treatments for severe preeclampsia?

Ravulizumab is unique because it is a monoclonal antibody that targets and inhibits complement protein C5, which is involved in the body's immune response. This approach is similar to Eculizumab, another complement inhibitor, and may help improve symptoms and prolong pregnancy in severe preeclampsia cases, unlike traditional treatments that focus on managing symptoms like high blood pressure. ^{4 5 6 7 8}

Research Team

Maria Lourdes Gonzalez Suarez, MD, PhD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for pregnant individuals with severe preeclampsia or HELLP syndrome, which involves high blood pressure and other complications. Specific eligibility details are not provided, but typically participants must meet certain health standards to ensure safety.

Inclusion Criteria

Individuals with severe preeclampsia or HELLP features

Individuals with < 34 0/7 weeks of gestation

Exclusion Criteria

Individuals with non-viable fetuses

Individuals with allergy to Ravulizumab

I have been diagnosed with paroxysmal nocturnal hemoglobinuria.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Subjects will receive a single-dose infusion of Ravulizumab

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 weeks

2 visits (in-person)

Treatment Details

Interventions

• Ravulizumab

Trial Overview The study is examining the effectiveness of ravulizumab in treating severe preeclampsia and HELLP syndrome during pregnancy. The goal is to see if this medication can help manage these conditions.

Participant Groups

Group I: Revulizumab Treatment Experimental Treatment 1 Intervention

Subjects will receive an single-dose infusion of Ravulizumab.

Ravulizumab is already approved in United States, European Union for the following indications:

Approved in United States as Ultomiris for:

• Paroxysmal nocturnal hemoglobinuria (PNH)
• Atypical hemolytic uremic syndrome (aHUS)

Approved in European Union as Ultomiris for:

• Paroxysmal nocturnal haemoglobinuria (PNH)

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

In a study involving 1009 high-risk pregnant women, low dose aspirin (60 mg) did not significantly reduce the incidence of pre-eclampsia or related complications compared to a placebo.

The study found no increase in maternal or fetal bleeding associated with aspirin use, but overall, the results do not support the routine use of low dose aspirin for preventing pre-eclampsia in high-risk women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ECPPA: randomised trial of low dose aspirin for the prevention of maternal and fetal complications in high risk pregnant women. ECPPA (Estudo Colaborativo para Prevenção da Pré-eclampsia com Aspirina) Collaborative Group. [2019]

Preeclampsia is a major cause of maternal mortality and can lead to serious health issues for newborns, highlighting the urgent need for new treatments.

Current drug development for preeclampsia has been limited, with existing treatments showing varying success, emphasizing the importance of targeting the underlying causes of the condition to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug development in preeclampsia: a 'no go' area? Everett, TR., Wilkinson, IB., Lees, CC.[2022]

In a mouse model of preeclampsia, sulfasalazine showed a modest initial effect in reducing diastolic and mean blood pressure, but this effect did not persist throughout gestation, indicating limited efficacy as a long-term treatment.

Sulfasalazine did not improve fetal growth or size, which are critical outcomes for a successful preeclampsia therapy, suggesting that while it may have some potential to enhance vascular function, it is not a viable treatment option in its current form.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulfasalazine for the treatment of preeclampsia in a nitric oxide synthase antagonist mouse model. Binder, NK., de Alwis, N., Beard, S., et al.[2023]

The KOUNO-TORI study is a phase 3 clinical trial designed to evaluate the efficacy and safety of recombinant human antithrombin gamma (rhAT-gamma) in treating early-onset severe preeclampsia in pregnant women between 24 and 32 weeks gestation, focusing on prolonging pregnancy duration.

This study aims to provide critical data on maternal and neonatal outcomes, potentially identifying rhAT-gamma as a novel treatment option for patients with early-onset severe preeclampsia, a condition with limited effective treatments available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase 3 trial evaluating antithrombin gamma treatment in Japanese patients with early-onset severe preeclampsia (KOUNO-TORI study): Study protocol. Saito, S., Takagi, K., Moriya, J., et al.[2022]

Pravastatin has emerged as a promising candidate for preventing preeclampsia, showing beneficial effects in preclinical studies and early clinical trials, with several large prevention trials currently underway to confirm its efficacy.

Other potential treatments, including proton-pump inhibitors, metformin, and natural compounds, are also being evaluated for their ability to target the underlying mechanisms of preeclampsia, indicating a broad interest in repurposing existing drugs and exploring new therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pravastatin, proton-pump inhibitors, metformin, micronutrients, and biologics: new horizons for the prevention or treatment of preeclampsia. Tong, S., Kaitu'u-Lino, TJ., Hastie, R., et al.[2022]

A case study of a patient with severe preeclampsia/HELLP syndrome at 26 weeks gestation showed that treatment with Eculizumab, a complement protein C5 inhibitor, led to significant clinical improvement and normalization of laboratory parameters.

The use of Eculizumab allowed for a 17-day prolongation of the pregnancy, potentially reducing neonatal morbidity and associated healthcare costs, indicating that complement inhibition could be a promising treatment strategy for severe preeclampsia/HELLP syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eculizumab for the treatment of preeclampsia/HELLP syndrome. Burwick, RM., Feinberg, BB.[2022]

In a severe case of preeclampsia with HELLP syndrome and acute kidney injury, treatment with eculizumab, a monoclonal antibody targeting complement protein C5, led to significant improvements in kidney and liver function one week after administration.

The patient's blood pressure normalized and the need for renal replacement therapy was discontinued, suggesting that complement activation plays a critical role in the pathogenesis of preeclampsia and that eculizumab may be a beneficial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eculizumab, a novel potential treatment for acute kidney injury associated with preeclampsia/HELLP syndrome. Elabd, H., Elkholi, M., Steinberg, L., et al.[2021]

Expectant management of severe preeclampsia in selected women between 24 and 32 weeks of gestation can be safe and may improve neonatal outcomes, based on a review of studies involving 1677 women.

For pregnancies less than 24 weeks, expectant management is linked to high maternal morbidity with minimal benefits for the fetus, indicating that careful selection of candidates for this approach is crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications. Sibai, BM., Barton, JR.[2007]

References

1. England pubmed.ncbi.nlm.nih.gov

ECPPA: randomised trial of low dose aspirin for the prevention of maternal and fetal complications in high risk pregnant women. ECPPA (Estudo Colaborativo para Prevenção da Pré-eclampsia com Aspirina) Collaborative Group. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Drug development in preeclampsia: a 'no go' area? [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Sulfasalazine for the treatment of preeclampsia in a nitric oxide synthase antagonist mouse model. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

A randomized phase 3 trial evaluating antithrombin gamma treatment in Japanese patients with early-onset severe preeclampsia (KOUNO-TORI study): Study protocol. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Pravastatin, proton-pump inhibitors, metformin, micronutrients, and biologics: new horizons for the prevention or treatment of preeclampsia. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Eculizumab for the treatment of preeclampsia/HELLP syndrome. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Eculizumab, a novel potential treatment for acute kidney injury associated with preeclampsia/HELLP syndrome. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications. [2007]