Certolizumab for Pregnancy Complications Due to APS

Recruiting at 2 trial locations

Overseen By Rose Peckham

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Ware Branch

Must be taking: Certolizumab

Must not be taking: Prednisone

Disqualifiers: Hypertension, Diabetes, SLE, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 19 weeks

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding the drug certolizumab (also known as Cimzia or Certolizumab Pegol) can improve pregnancy outcomes for women with antiphospholipid syndrome (APS), a condition that can cause pregnancy complications. All participants will receive certolizumab along with the usual treatment of heparin and low-dose aspirin. The trial aims to determine if this combination is more effective than the standard treatment alone. Women who are pregnant with APS and have tested positive for lupus anticoagulant might be suitable candidates for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking findings.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does require you to continue with usual treatment, which includes a heparin agent and low-dose aspirin.

Is there any evidence suggesting that certolizumab is likely to be safe for pregnant women with APS?

Research has shown that certolizumab might help prevent pregnancy complications in women with antiphospholipid syndrome (APS). Studies have found that it can reduce placental issues, which are crucial for a healthy pregnancy. In these studies, women who took certolizumab typically delivered their babies around 36.5 weeks, suggesting it is generally safe during pregnancy.

Certolizumab is already approved for other conditions, indicating it is usually well-tolerated. While specific side effects during pregnancy aren't detailed, its use in other treatments provides some confidence in its safety. As this trial is in an early stage, further research will help confirm these findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pregnancy complications due to Antiphospholipid Syndrome (APS), which typically involve heparin and low-dose aspirin, Certolizumab Pegol offers a unique approach. Certolizumab Pegol is a biologic that targets and neutralizes tumor necrosis factor-alpha (TNF-alpha), a molecule involved in inflammation, which is not addressed by current standard care. Researchers are excited about this treatment because it could reduce inflammation-related complications during pregnancy, offering a new mechanism of action that may improve outcomes for mothers and babies. Additionally, its administration through subcutaneous injections could provide a more convenient and potentially more effective option for managing APS during pregnancy.

What evidence suggests that certolizumab might be an effective treatment for pregnancy complications due to APS?

Research has shown that certolizumab pegol, which participants in this trial will receive, may help prevent pregnancy problems in women with antiphospholipid syndrome (APS). In one study, only 20% of women taking certolizumab experienced complications, compared to 69% to 79% in past pregnancies for similar patients. This suggests certolizumab could improve pregnancy outcomes for women with APS and lupus anticoagulant (LAC). The treatment appears to address issues related to the placenta, which is crucial for a healthy pregnancy. These promising results highlight certolizumab's potential benefits for high-risk pregnancies. ^{1 2 3 6 7}

Who Is on the Research Team?

D. Ware Branch, MD

Principal Investigator

University of Utah

Are You a Good Fit for This Trial?

This trial is for pregnant women aged 18-40 with antiphospholipid syndrome (APS) and lupus anticoagulant (LAC), who are less than 8 weeks into their pregnancy. They must have a hematocrit >26% and no history of diabetes, multifetal gestation, certain infections like HIV or tuberculosis, high blood pressure at screening, or be on high doses of prednisone.

Inclusion Criteria

Pregnant as defined by positive test for elevated ß-HCG and having a live, appropriate sized embryo by ultrasound, but <8 weeks gestation

I have tested positive for LAC twice over 12 weeks apart in the last 18 months.

I have been diagnosed with antiphospholipid syndrome.

Exclusion Criteria

Multifetal gestation

Type 1 or Type 2 diabetes antedating pregnancy

My urine protein levels are high.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive certolizumab starting by 8 weeks and 6 days gestation, with doses at 2 and 4 weeks later, followed by every other week until 27 weeks and 6 days gestation

19 weeks

Initial visit for first dose, followed by bi-weekly visits for subsequent doses

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of pregnancy outcomes and adverse events

6 weeks postpartum

Postpartum Monitoring

Participants are monitored for any adverse outcomes or pertinent concerns related to the study intervention

6 weeks postpartum

What Are the Treatments Tested in This Trial?

Interventions

• Certolizumab Pegol

Trial Overview The IMPACT study tests whether adding certolizumab to standard treatment (heparin agent and low-dose aspirin) improves pregnancy outcomes in APS patients with positive LAC tests. All participants receive certolizumab; results will be compared to historical data from similar patients.

How Is the Trial Designed?

Group I: Certolizumab Pegol Experimental Treatment 1 Intervention

All participants are administered certolizumab \[400 mg (given as two subcutaneous injections of 200mg) initially and 2 and 4 weeks later, followed by 200 mg every other week thereafter. 1st dose of certolizumab will be administered by 8 weeks and 6 days gestation and discontinued at 27 weeks 6 days. The regimen of heparin and low dose aspirin is a standard of care treatment for this patient population and is not considered part of the research intervention.

Who Is Running the Clinical Trial?

Ware Branch

Lead Sponsor

Trials

2

Recruited

1,300+

David Ware Branch

Lead Sponsor

Trials

1

Recruited

60+

Hospital for Special Surgery, New York

Collaborator

Trials

257

Recruited

61,800+

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

NYU Langone Health

Collaborator

Trials

1,431

Recruited

838,000+

Published Research Related to This Trial

Intravenous immunoglobulin (IVIg) therapy shows promising efficacy for treating recurrent pregnancy loss in Antiphospholipid Syndrome (APS), with reported success rates between 70-100% when administered in specific regimens during early pregnancy.

Compared to traditional treatments like prednisone and low-dose aspirin or heparin, IVIg appears to reduce complications such as pre-eclampsia and intrauterine growth retardation, making it a potentially safer and more effective option despite its higher cost.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization of intravenous immunoglobulin therapy to treat recurrent pregnancy loss in the antiphospholipid syndrome: a review. Harris, EN., Pierangeli, SS.[2022]

In a review of 1392 pregnancies exposed to certolizumab pegol (CZP), a TNF inhibitor, 88.4% resulted in live births, indicating a favorable outcome for pregnancies during CZP treatment.

There were no significant signals for adverse pregnancy outcomes or congenital malformations associated with CZP exposure, providing reassurance for women with chronic inflammatory diseases considering this treatment during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacovigilance pregnancy data in a large population of patients with chronic inflammatory disease exposed to certolizumab pegol. Clowse, M., Fischer-Betz, R., Nelson-Piercy, C., et al.[2022]

In a study of 1,137 pregnancies with maternal exposure to certolizumab pegol (CZP), 85.3% resulted in live births, indicating that CZP is generally safe for use during pregnancy.

The analysis found no evidence of teratogenic effects or increased risk of fetal death associated with CZP, providing reassurance for women of childbearing age considering this treatment for chronic inflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnancy Outcomes After Exposure to Certolizumab Pegol: Updated Results From a Pharmacovigilance Safety Database. Clowse, MEB., Scheuerle, AE., Chambers, C., et al.[2019]

A case report highlights a successful pregnancy in a patient with antiphospholipid antibody syndrome (APS) and severe thrombocytopenia, treated with intravenous rituximab and immunoglobulin (IvIg), marking a potential new approach for similar cases.

This is the first documented instance of a positive pregnancy outcome using rituximab in conjunction with IvIg for APS patients facing severe complications, suggesting that these treatments may be considered for patients who do not respond to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of successful pregnancy following multidrug treatment including rituximab and intravenous immunoglobulin for primary antiphospholipid antibody syndrome refractory to conventional treatment. Nagata, M., Kaneko, K., Kohno, C., et al.[2021]

In a study of 1650 women with antiphospholipid syndrome (APS), significant clinical and laboratory differences were found between those who met the Sydney criteria for obstetric APS (OAPS) and those who did not (non-criteria OAPS, NC-OAPS), particularly in the prevalence of aPL laboratory categories.

Despite these differences, fetal-maternal outcomes, including live births and thrombotic complications, were similar between the two groups when treated, indicating that treatment may be effective regardless of whether patients meet the Sydney criteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of obstetric antiphospholipid syndrome (OAPS) and non-criteria obstetric APS (NC-OAPS): report of 1640 cases from the EUROAPS registry. Alijotas-Reig, J., Esteve-Valverde, E., Ferrer-Oliveras, R., et al.[2021]

In a study of 30 patients with antiphospholipid syndrome (APS) involving 35 pregnancies, the use of hydroxychloroquine significantly reduced pregnancy losses from 81% to 19% when compared to previous treatments (p<0.05).

Among 14 patients with a history of refractory obstetrical APS, the addition of hydroxychloroquine led to successful live births in 78% of cases, highlighting its potential effectiveness in improving pregnancy outcomes for these high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: Data from a European multicenter retrospective study. Mekinian, A., Lazzaroni, MG., Kuzenko, A., et al.[2018]

In a study involving 16 pregnant women receiving certolizumab pegol (CZP), the drug showed minimal to no transfer to infants at birth, indicating low fetal exposure during the third trimester.

The findings support the continued use of CZP during pregnancy for women with chronic inflammatory diseases, as it appears to be safe for the developing fetus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study. Mariette, X., Förger, F., Abraham, B., et al.[2019]

Certolizumab pegol (Cimzia®) has been shown to significantly improve psoriasis symptoms in adults, with more patients achieving a 75% reduction in PASI score compared to placebo in phase III trials involving moderate to severe plaque psoriasis.

This medication is particularly beneficial for women of childbearing age due to its unique properties, such as minimal placental transfer and low infant exposure during breastfeeding, while maintaining a good safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Certolizumab Pegol: A Review in Moderate to Severe Plaque Psoriasis. Lee, A., Scott, LJ.[2021]

Subcutaneous heparin and low-dose aspirin are effective standard therapies for pregnant women with antiphospholipid antibodies (aPL) and a history of fetal loss, supported by recent randomized controlled trials.

For women who do not respond to aspirin and heparin, intravenous immunoglobulin may be a beneficial additional treatment option, while prednisone is generally avoided due to its high risk of complications for both mother and fetus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the management of the pregnant patient with antiphospholipid antibody. Sammaritano, LR.[2019]

In a review of 625 reported pregnancies involving certolizumab pegol (CZP), 372 had known outcomes, showing that maternal exposure resulted in 254 live births and a miscarriage rate of 15.3%, suggesting that CZP does not significantly harm pregnancy outcomes.

The majority of pregnancies were exposed to CZP during the first trimester, and while there were some reports of congenital malformations and one neonatal death, the overall findings indicate that maternal CZP exposure does not appear to adversely affect pregnancy outcomes, although more extensive studies are needed for conclusive safety assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnancy Outcomes in Subjects Exposed to Certolizumab Pegol. Clowse, ME., Wolf, DC., Förger, F., et al.[2019]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003496725002432

Certolizumab pegol to prevent adverse pregnancy ... Certolizumab appears effective in preventing placenta-mediated adverse outcomes in high-risk patients with APS.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40483169/

results of a prospective, single-arm, open-label, phase 2 trial Certolizumab appears effective in preventing placenta-mediated adverse outcomes in high-risk patients with APS.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03152058

NCT03152058 | IMPACT Study: IMProve Pregnancy in ... All enrolled patients will receive certolizumab, and pregnancy outcomes will be compared to those of women with APS and repeatedly positive tests for LAC ...

4. lupus.org lupus.org/news/study-finds-certolizumab-pegol-may-improve-pregnancy-outcomes-in-women-with-lupus-and

Study Finds Certolizumab Pegol May Improve Pregnancy ... The 20% complication rate with certolizumab was dramatically lower than IMPACT participants' prior pregnancies; 69% to 79% had severe adverse ...

5. nature.com nature.com/nature-index/article/10.1016/j.ard.2025.02.012

results of a prospective, single-arm, open-label, phase 2 trial Certolizumab pegol to prevent adverse pregnancy outcomes in patients with antiphospholipid syndrome and lupus anticoagulant (IMPACT): results ...

6. rheumnow.com rheumnow.com/news/add-certolizumab-pregnant-women-aps

Add-on certolizumab in pregnant women with APS Women with antiphospholipid syndrome and lupus anti-coagulant are at high risk of developing adverse pregnancy outcomes (APO).

7. ard.eular.org ard.eular.org/article/S0003-4967(25)00243-2/abstract

Certolizumab pegol to prevent adverse pregnancy outcomes ... Median gestational age at delivery in certolizumab-treated patients was 36.5 weeks and was after 30 weeks in those who met the primary outcome of pre-eclampsia.