IMPACT Study: IMProve Pregnancy in APS With Certolizumab Therapy

NCT03152058 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 94818
• Study Type: interventional
• Target: 55
• Locations: 2 countries
• Sites: 3

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Fetal death and/or preterm delivery (<34 weeks) due to PE or PI in women with APS and LAC

  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 Outcomes (1)

• Additional adverse outcomes or pertinent concerns, possibly related to study intervention

  8 weeks gestation through 6-weeks postpartum

Study Arms (1)

Certolizumab Pegol

EXPERIMENTAL

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

Interventions

Certolizumab Pegol DRUG

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.

Also known as: Cimzia

Certolizumab Pegol

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Eligibility includes only pregnant women
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Active infection, e.g., chronic hepatitis B
• History of recurrent infection, e.g., recurrent cellulitis, or opportunistic infection

Sponsors & Collaborators

• Hospital for Special Surgery, New York: collaborator
• University of Toronto: collaborator
• David Ware Branch: lead
• NYU Langone Health: collaborator

Study Sites (3)

Hospital for Special Surgery

New York, New York, 10021, United States

RECRUITING

University of Utah

Salt Lake City, Utah, 84132, United States

RECRUITING

TRIO Advancing Reproductive Care

Toronto, Ontario, M5G 2K4, Canada

RECRUITING

Related Publications (22)

• Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295-306. doi: 10.1111/j.1538-7836.2006.01753.x.

  PMID: 16420554 BACKGROUND

• Committee on Practice Bulletins-Obstetrics, American College of Obstetricians and Gynecologists. Practice Bulletin No. 132: Antiphospholipid syndrome. Obstet Gynecol. 2012 Dec;120(6):1514-21. doi: 10.1097/01.AOG.0000423816.39542.0f.

  PMID: 23168789 BACKGROUND

• Andreoli L, Chighizola CB, Banzato A, Pons-Estel GJ, Ramire de Jesus G, Erkan D. Estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis: a critical review of the literature. Arthritis Care Res (Hoboken). 2013 Nov;65(11):1869-73. doi: 10.1002/acr.22066.

  PMID: 23861221 BACKGROUND

• Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet. 2010 Oct 30;376(9751):1498-509. doi: 10.1016/S0140-6736(10)60709-X. Epub 2010 Sep 6.

  PMID: 20822807 BACKGROUND

• de Jesus GR, Agmon-Levin N, Andrade CA, Andreoli L, Chighizola CB, Porter TF, Salmon J, Silver RM, Tincani A, Branch DW. 14th International Congress on Antiphospholipid Antibodies Task Force report on obstetric antiphospholipid syndrome. Autoimmun Rev. 2014 Aug;13(8):795-813. doi: 10.1016/j.autrev.2014.02.003. Epub 2014 Mar 17.

  PMID: 24650941 BACKGROUND

• Girardi G, Berman J, Redecha P, Spruce L, Thurman JM, Kraus D, Hollmann TJ, Casali P, Caroll MC, Wetsel RA, Lambris JD, Holers VM, Salmon JE. Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J Clin Invest. 2003 Dec;112(11):1644-54. doi: 10.1172/JCI18817.

  PMID: 14660741 BACKGROUND

• Shamonki JM, Salmon JE, Hyjek E, Baergen RN. Excessive complement activation is associated with placental injury in patients with antiphospholipid antibodies. Am J Obstet Gynecol. 2007 Feb;196(2):167.e1-5. doi: 10.1016/j.ajog.2006.10.879.

  PMID: 17306667 BACKGROUND

• Stone S, Pijnenborg R, Vercruysse L, Poston R, Khamashta MA, Hunt BJ, Poston L. The placental bed in pregnancies complicated by primary antiphospholipid syndrome. Placenta. 2006 Apr-May;27(4-5):457-67. doi: 10.1016/j.placenta.2005.04.006. Epub 2005 Jul 6.

  PMID: 16005063 BACKGROUND

• Lockshin MD, Kim M, Laskin CA, Guerra M, Branch DW, Merrill J, Petri M, Porter TF, Sammaritano L, Stephenson MD, Buyon J, Salmon JE. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum. 2012 Jul;64(7):2311-8. doi: 10.1002/art.34402.

  PMID: 22275304 BACKGROUND

• Gilbert WM, Nesbitt TS, Danielsen B. The cost of prematurity: quantification by gestational age and birth weight. Obstet Gynecol. 2003 Sep;102(3):488-92. doi: 10.1016/s0029-7844(03)00617-3.

  PMID: 12962929 BACKGROUND

• Gnanendran L, Bajuk B, Oei J, Lui K, Abdel-Latif ME; NICUS Network. Neurodevelopmental outcomes of preterm singletons, twins and higher-order gestations: a population-based cohort study. Arch Dis Child Fetal Neonatal Ed. 2015 Mar;100(2):F106-14. doi: 10.1136/archdischild-2013-305677. Epub 2014 Oct 30.

  PMID: 25359876 BACKGROUND

• Pijnenborg R, Vercruysse L, Hanssens M. The uterine spiral arteries in human pregnancy: facts and controversies. Placenta. 2006 Sep-Oct;27(9-10):939-58. doi: 10.1016/j.placenta.2005.12.006. Epub 2006 Feb 20.

  PMID: 16490251 BACKGROUND

• Redman CW, Sargent IL. Immunology of pre-eclampsia. Am J Reprod Immunol. 2010 Jun;63(6):534-43. doi: 10.1111/j.1600-0897.2010.00831.x. Epub 2010 Mar 23.

  PMID: 20331588 BACKGROUND

• Berman J, Girardi G, Salmon JE. TNF-alpha is a critical effector and a target for therapy in antiphospholipid antibody-induced pregnancy loss. J Immunol. 2005 Jan 1;174(1):485-90. doi: 10.4049/jimmunol.174.1.485.

  PMID: 15611274 BACKGROUND

• Redecha P, Tilley R, Tencati M, Salmon JE, Kirchhofer D, Mackman N, Girardi G. Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury. Blood. 2007 Oct 1;110(7):2423-31. doi: 10.1182/blood-2007-01-070631. Epub 2007 May 29.

  PMID: 17536017 BACKGROUND

• Qing X, Redecha PB, Burmeister MA, Tomlinson S, D'Agati VD, Davisson RL, Salmon JE. Targeted inhibition of complement activation prevents features of preeclampsia in mice. Kidney Int. 2011 Feb;79(3):331-9. doi: 10.1038/ki.2010.393. Epub 2010 Oct 13.

  PMID: 20944547 BACKGROUND

• Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, Libermann TA, Morgan JP, Sellke FW, Stillman IE, Epstein FH, Sukhatme VP, Karumanchi SA. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003 Mar;111(5):649-58. doi: 10.1172/JCI17189.

  PMID: 12618519 BACKGROUND

• Lubbe WF, Butler WS, Palmer SJ, Liggins GC. Fetal survival after prednisone suppression of maternal lupus-anticoagulant. Lancet. 1983 Jun 18;1(8338):1361-3. doi: 10.1016/s0140-6736(83)92141-4.

  PMID: 6134138 BACKGROUND

• Branch DW, Scott JR, Kochenour NK, Hershgold E. Obstetric complications associated with the lupus anticoagulant. N Engl J Med. 1985 Nov 21;313(21):1322-6. doi: 10.1056/NEJM198511213132104.

  PMID: 3932854 BACKGROUND

• Cowchock FS, Reece EA, Balaban D, Branch DW, Plouffe L. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment. Am J Obstet Gynecol. 1992 May;166(5):1318-23. doi: 10.1016/0002-9378(92)91596-3.

  PMID: 1595785 BACKGROUND

• Yelnik CM, Laskin CA, Porter TF, Branch DW, Buyon JP, Guerra MM, Lockshin MD, Petri M, Merrill JT, Sammaritano LR, Kim MY, Salmon JE. Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: validation of PROMISSE study results. Lupus Sci Med. 2016 Jan 12;3(1):e000131. doi: 10.1136/lupus-2015-000131. eCollection 2016.

  PMID: 26835148 BACKGROUND

• Clark CA, Laskin CA, Spitzer KA. Anticardiolipin antibodies and recurrent early pregnancy loss: a century of equivocal evidence. Hum Reprod Update. 2012 Sep-Oct;18(5):474-84. doi: 10.1093/humupd/dms020. Epub 2012 Jun 13.

  PMID: 22699010 BACKGROUND

MeSH Terms

Conditions

Pregnancy Complications

Interventions

Certolizumab Pegol

Condition Hierarchy (Ancestors)

Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• D. Ware Branch, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rose Peckham

CONTACT

801-585-7617; Rose.Peckham@hsc.utah.edu

Elizabeth Turner

CONTACT

801-585-0591; elizabeth.e.turner@hsc.utah.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 1, 2017
• First Posted: May 12, 2017
• Study Start: May 17, 2017
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); CA (1)