Improving pregnancy outcomes in women with antiphospholipid syndrome using certolizumab

Certolizumab to Prevent Pregnancy Complications in High-Risk Patients With APS or SLE - (IMPACT Study: IMProve Pregnancy in APS With Certolizumab Therapy)

This study is testing if adding a medication called certolizumab to standard treatment can help women with antiphospholipid syndrome have healthier pregnancies.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Ages: 18 Years to 40 Years
• Sex: Female
• Sponsor: University of Utah (Academic / other)
• Drugs / interventions: certolizumab, prednisone
• Locations: 3 sites (New York, New York and 2 other locations)
• Trial ID: NCT03152058 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of certolizumab, an anti-tumor necrosis factor-alpha drug, in improving pregnancy outcomes for women with antiphospholipid syndrome (APS) and positive lupus anticoagulant tests. Participants will receive certolizumab in addition to standard treatment with heparin and low-dose aspirin. The study aims to determine if this combination therapy can reduce adverse pregnancy outcomes, such as fetal loss and preterm birth, by addressing inflammation and improving placental vascularization. Outcomes will be compared to data from a previous observational study involving similar patients.

Who should consider this trial

Good fit: Ideal candidates are pregnant women aged 18-40 with a diagnosis of antiphospholipid syndrome and positive lupus anticoagulant tests.

Not a fit: Patients who do not have antiphospholipid syndrome or those with severe comorbid conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve pregnancy outcomes for women with antiphospholipid syndrome.

How similar studies have performed: Previous studies have shown promising results with similar approaches, particularly in mouse models, but this specific combination therapy is novel in the context of human pregnancy.

Eligibility criteria

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;
* Antiphospholipid syndrome (APS);
* Positive for LAC on two or more occasions greater than 12 weeks apart within the previous 18 months. If a candidate for the study is newly diagnosed (\<12 weeks) with APS, meets clinical criteria for APS and has one positive LAC confirmed by review of the medical record, she may be consented and screened. At baseline, LAC will be measured at the study core lab and she will be enrolled if it is found to be positive. The LAC measurement will be repeated 12 weeks after the initial determination and, if positive, she will remain in the study.
* Age 18-40 (+364 days) years of age and able to give informed consent
* Laboratory hematocrit \>26% at time of screening.

the diagnosis of APS and LAC will be confirmed by one of the Co-PI's for each case by a review of the medical records.

Exclusion Criteria:

* Hypertension (BP \>140/90) present at screening;
* Multifetal gestation;
* Type 1 or Type 2 diabetes antedating pregnancy;
* SLE patients requiring prednisone \>10 mg/day;
* Platelet count \<100,000 per microliter;
* Women currently taking prednisone greater than 10 mg daily for an autoimmune disorder, other than immune thrombocytopenia;

  a. More than 60 mg once daily in a tapering regimen or 20 mg once daily in a maintenance regimen for immune thrombocytopenia
* Women with urinary excretion with greater than 500 mg (0.5 g) per day (spot urine protein/creatinine ration 0.5);
* Serum creatinine \>1.2 mg/dL
* History of tuberculosis or untreated positive PPD;
* Women with a tuberculin skin test induration of 5 mm or greater; or positive quantiFERON-gold test
* Women with HIV, Hepatitis B or Hepatitis C positive status;
* Known contraindications or relative contraindications to certolizumab:

  1. Active infection, e.g., chronic hepatitis B
  2. History of recurrent infection, e.g., recurrent cellulitis, or opportunistic infection
  3. History of prior active/treated endemic mycoses in the last two years (including coccidioidomycosis, blastomycosis, or histoplasmosis)
  4. History of heart failure
  5. History of peripheral demyelinating disease or Guillian-Barre syndrome
  6. History of hematologic malignancy
  7. Prior adverse reaction to certolizumab or o ther anti-TNF-α agent

Where this trial is running

New York, New York and 2 other locations

• Hospital for Special Surgery — New York, New York, United States (Recruiting)
• University of Utah — Salt Lake City, Utah, United States (Recruiting)
• TRIO Advancing Reproductive Care — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: D. Ware Branch, MD — University of Utah
• Study coordinator: Rose Peckham

Conditions High Risk Pregnancy; Pregnancy Complications; Antiphospholipid Syndrome in Pregnancy; Lupus Anticoagulant Disorder