IMPACT Study: IMProve Pregnancy in APS With Certolizumab Therapy

March 27, 2026 updated by: David Ware Branch

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

This treatment trial evaluates the addition of an anti-tumor necrosis factor-alpha drug, certolizumab, to usual treatment (a heparin agent and low-dose aspirin) in pregnant women with antiphospholipid syndrome (APS) and repeatedly positive tests for lupus anticoagulant (LAC) to determine if this regimen will improve pregnancy outcomes. All enrolled patients will receive certolizumab, and pregnancy outcomes will be compared to those of women with APS and repeatedly positive tests for LAC enrolled in a previous study by the investigators.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Antiphospholipid syndrome (APS) is an autoimmune disorder that occurs most commonly in women of reproductive-age and is associated with thrombosis and adverse pregnancy outcomes (APOs), such as fetal loss and preterm birth due to severe preeclampsia (PE) or placental insufficiency (PI). Traditional therapy for APS during pregnancy has been a heparin agent and low dose aspirin. However, in PROMISSE, a prospective observational study of 724 patients, 44% of pregnancies in women with APS and LAC resulted in APOs despite treatment with heparin and low dose aspirin.

The APOs in women with APS and LAC are due to failure of adequate vascularization of the developing placenta and subsequent inadequate blood flow to the placenta and fetus. Mouse models of APS show that poor placental vascularization in APS is a result of inflammation in the placenta. This inflammation leads to recruitment of neutrophils and release of more inflammatory mediators and anti-angiogenic factors. In the mouse model tumor necrosis factor-alpha is a critical downstream effector of abnormal placental development and fetal damage, and tumor necrosis factor-alpha blockade during pregnancy restores angiogenic balance, normalizes placental vascularization, and rescues pregnancies.

Based on our observations in PROMISSE and the favorable results of tumor necrosis factor-alpha blockade in our mouse models, we hypothesize that tumor necrosis factor-alpha blockade will significantly decrease the rate of fetal death and preterm delivery due to PE and PI in women with APS and LAC. The study investigators aim to determine whether tumor necrosis factor-alpha blockade during pregnancy, added to a regimen of heparin and low dose aspirin, (1) reduces the rate of APOs in women with clinical APS and LAC, and (2) alters angiogenic markers of poor placental vascularization. Investigators will conduct an open label trial of certolizumab (a tumor necrosis factor-alpha inhibitor that does not cross the placenta). The regimen of heparin and low dose aspiring is a standard of care treatment for this patient population and is not considered part of the research intervention.

Study Type

Interventional

Enrollment (Estimated)

55

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2K4
        • Recruiting
        • TRIO Advancing Reproductive Care
        • Contact:
        • Principal Investigator:
          • Carl Laskin, MD
  • United States
    • New York
      • New York, New York, United States, 10021
        • Recruiting
        • Hospital For Special Surgery
        • Contact:
        • Principal Investigator:
          • Jane Salmon, MD
    • Utah
      • Salt Lake City, Utah, United States, 84132

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 38 years (Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Certolizumab Pegol

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.
Drug: Certolizumab Pegol

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] The 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.

Other Names:
  • Cimzia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fetal death and/or preterm delivery (<34 weeks) due to PE or PI in women with APS and LAC
Time Frame: 8 weeks gestation through 6-weeks postpartum

Either of the following will constitute a primary outcome:

  1. Fetal death (>10 wks gestation)
  2. Severe preeclampsia or placental insufficiency requiring delivery prior to 34 weeks gestation.
8 weeks gestation through 6-weeks postpartum

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Additional adverse outcomes or pertinent concerns, possibly related to study intervention
Time Frame: 8 weeks gestation through 6-weeks postpartum

Any one of the following is considered a secondary outcome:

  1. Neonatal death due to complications of prematurity because of preterm delivery for PE or PI
  2. Preterm labor or preterm rupture of membranes resulting in delivery prior to 36 weeks gestation
  3. PE or PI not requiring delivery prior to 34 weeks gestation
  4. Gestational age at delivery
  5. Maternal thrombosis
  6. Small-for-gestational age birthweight (<10th percentile)
  7. Known adverse reactions to certolizumab.
8 weeks gestation through 6-weeks postpartum

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

David Ware Branch

Collaborators

NYU Langone Health
University of Toronto
Hospital for Special Surgery, New York

Investigators

  • Principal Investigator: D. Ware Branch, MD, University of Utah

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 17, 2017

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

May 1, 2017

First Submitted That Met QC Criteria

May 10, 2017

First Posted (Actual)

May 12, 2017

Study Record Updates

Last Update Posted (Actual)

April 1, 2026

Last Update Submitted That Met QC Criteria

March 27, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 94818

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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