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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called ravulizumab (also known as Ultomiris) to determine its effectiveness in treating severe preeclampsia and HELLP syndrome, serious conditions that can occur during pregnancy. The goal is to see if ravulizumab can improve the health of pregnant individuals and their babies by reducing symptoms like high blood pressure and liver problems. Participants will receive a single-dose infusion of the medication. The trial seeks pregnant individuals who are less than 34 weeks along and have severe preeclampsia or HELLP syndrome. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people, offering participants a chance to contribute to important medical advancements.

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 there any evidence suggesting that ravulizumab is likely to be safe for humans?

Research has shown that ravulizumab is well-tolerated in other health conditions. One study with patients who have paroxysmal nocturnal hemoglobinuria (PNH) used ravulizumab safely for 5.6 years. Most side effects were mild, such as headaches and nausea, affecting at least 10% of patients. Other studies have found that ravulizumab is generally safe during pregnancy, with researchers examining its effects on both the mother and the baby. Although these results come from different conditions, they suggest that ravulizumab could be safe for treating severe preeclampsia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for severe preeclampsia primarily involve managing symptoms, such as controlling blood pressure with medications like labetalol or hydralazine, and often require early delivery of the baby. But Ravulizumab works differently, targeting the root cause by inhibiting the complement system, a part of the immune system that can become overactive in preeclampsia. This unique mechanism could potentially prevent the progression of the disease rather than just managing its symptoms. Researchers are excited because this approach might offer a more effective way to treat severe preeclampsia, potentially benefiting both the mother and the baby.

What evidence suggests that ravulizumab might be an effective treatment for severe preeclampsia?

Research has shown that ravulizumab effectively treats immune system-related conditions, such as PNH, a blood disorder. It provides better and longer-lasting results compared to eculizumab. Ravulizumab blocks a part of the immune system that can cause inflammation and damage, potentially aiding in severe preeclampsia and HELLP syndrome. In this trial, participants will receive a single-dose infusion of ravulizumab to explore its potential for these conditions. Early findings suggest it could be beneficial due to its impact on the immune system. ^{1 2 5 6 7}

Who Is on the Research Team?

Maria Lourdes Gonzalez Suarez, MD, PhD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06333652

NCT06333652 | Ravulizumab in Pregnancies Complicated ... The researchers are testing a medication named ravulizumab for the treatment of severe preeclampsia and Hemolysis, Elevated Liver enzymes, Low Platelets (HELLP) ...

2. ultomirishcp.com ultomirishcp.com/pnh/efficacy-and-safety/adult-data

PNH | Adult data - ULTOMIRIS® (ravulizumab-cwvz) In clinical trials of adult patients with PNH, ULTOMIRIS showed robust & sustained efficacy across all endpoints vs. eculizumab, through 1+ year of ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK599307/

Clinical Review - Ravulizumab (Ultomiris) - NCBI - NIH Currently, eculizumab may be preferred over ravulizumab during pregnancy given the available efficacy and safety data for eculizumab although this may change as ...

4. mayo.edu mayo.edu/research/clinical-trials/cls-20564806

Ravulizumab in Pregnancies complicated by Severe ... The purpose of this study is to analyze the use of ravulizumab, an inhibitor of complement activation, to target alternative complement pathway in patients with ...

5. ultomiris.com ultomiris.com/pnh/ultomiris-results/efficacy-in-adults-and-children

Efficacy in adults and children The most common side effects (≥10%) of ULTOMIRIS in adults with PNH were upper respiratory tract infection and headache. These primary and secondary outcomes in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9546219/

Long‐term safety and efficacy of ravulizumab in patients ... Ravulizumab demonstrated durable efficacy and was well tolerated, highlighting the importance of C5 inhibitors as the mainstay of PNH treatment.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06312644

Study of Ultomiris® (Ravulizumab) Safety in Pregnancy The primary objective of this study is to describe the frequency and characteristics of pregnancy outcomes and maternal complications among participants exposed ...