Expanded Noninvasive Genomic Medical Assessment: The Enigma Study

NCT02787486 — Completed, 760 participants, Progenity, Inc.

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A Clinical Study to Evaluate the Relative Clinical Sensitivity, Specificity, and Performance of the a Laboratory Developed Test as a Screening Test for Fetal Chromosomal Aneuploidy, Infectious and Other Diseases, and RhD Genotyping in the General Population of Pregnant Women

Registry	NCT02787486
Status	Completed
Study type	Observational
Enrollment	760 (Actual)
Sponsor	Progenity, Inc. (Industry)
Conditions	Down Syndrome, Edwards Syndrome, Patau Syndrome, Klinefelter Syndrome, Turner Syndrome, DiGeorge Syndrome, Chromosome Deletion, Aneuploidy
Interventions	Blood sampling for Laboratory Developed Test (LDT) analysis (Other)
Dates	start 2015-10-01, primary completion 2018-09-01, completion 2018-09-01, first posted 2016-06-01, last updated 2019-08-21
Locations	8 sites in United States

-Summary

In January 2007, the American Congress of Obstetricians and Gynecologists (ACOG) revised its guidelines that now recommend physicians are ethically obligated to fully inform all pregnant women that screening for fetal chromosomal abnormalities including biochemical screening tests and invasive procedures such as CVS or amniocentesis is available, regardless of age. Further, it is entirely up to the patient to decide whether or not she wishes to be screened for fetal chromosomal abnormalities without judgment from the physician.

Noninvasive laboratory-developed tests (LDTs) that detect an abnormal amount of maternal and fetal DNA in an expectant mother's blood sample (known as circulating cell-free DNA) are now available. These LDTs have not been cleared or approved by the U.S. Food and Drug Administration (FDA). Although LDTs to date have not been subject to U.S. FDA regulation, certification of the laboratory is required under the Clinical Laboratory Improvement Amendments (CLIA) to ensure the quality and validity of the test.

To sample collection study will obtain whole blood specimens from pregnant subjects to be used for development of prenatal assays to assist in the screening for fetal genetic abnormalities, infectious and other diseases, and blood group typing through detection of circulating cell-free DNA extracted from maternal plasma.

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+Detailed description

Eligible subjects will provide written informed consent after which basic demographic and clinical data will be collected.

Study procedures involve the collection of 50 mL of whole blood at one or more monthly clinic visits (≥25 days apart) from pregnant women (18 to 54 yrs of age) carrying a single fetus of 8 to 22 weeks of gestational age inclusive.

+Arms and interventions

Arm	Type	Interventions	Description
Aneuploidy Arm		Other: Blood sampling for Laboratory Developed Test (LDT) analysis	Includes pregnant women at high risk for fetal chromosome aneuploidy for serum screening
TORCH Arm		Other: Blood sampling for Laboratory Developed Test (LDT) analysis	Infectious disease arm: Toxoplasmosis, other viruses, rubella, cytomegalovirus, and herpes simplex virus (TORCH). Includes pregnant women at low-risk for fetal aneuploidy that may be at increased risk for fetal infection for serum screening

Blood sampling for Laboratory Developed Test (LDT) analysis (Other): Each enrolled subject, either in the first or second trimester, will donate up to 50 mL (just over 3 tablespoons) of whole blood for development of the LDT

+Outcome measures

Primary outcomes

Point estimates and 95% CIs for sensitivity, specificity, PPV, and NPV versus birth outcome (trisomy or Unaffected/non-trisomy) for the LDT in the population of pregnancies at mixed-risk for chromosomal abnormalities [about 3 years]: Primary Objective

Secondary outcomes

To estimate the false positive rate of the LDT versus birth outcome (trisomy or Unaffected/ non-trisomy) in a low-risk sub-population of pregnant women undergoing serum biochemical screening for fetal aneuploidy. [about 3 years]

+Eligibility

Sex: Female, ages: 18 Years to 54 Years

Inclusion Criteria:

* Subject is willing to provide informed consent and comply with study procedures
* Pregnant female, 18 to 54 years of age carrying a singleton fetus of 8 to 22 weeks gestational age
* Willing to provide a study blood sample in accordance with the protocol
* Willing to allow access to her medical records to collect pregnancy outcome information
* Willing to provide consent for release of fetal karyotype if an invasive procedure (CVS or amniocentesis) is performed during the pregnancy
* Subject is known to be at risk for one or more of the following:
* fetal gene and chromosome abnormalities (e.g., T21, T18, T13, microdeletion syndromes, sex chromosome abnormalities)
* congenital fetal infection (e.g. toxoplasmosis, syphilis, HIV, rubella, CMV, HSV)
* irregular blood group antigens (subject or father of the baby)
* other condition amenable to noninvasive prenatal testing such as a single gene disorder (e.g., CF, sickle cell, Fragile X)

Exclusion Criteria:

* No fetal heart activity detected
* Mother or father have known chromosomal abnormalities (including known balanced translocations)
* Women with active or history of malignancy

+Locations (8)

Facility	City	Country
Valley Perinatal	Scottsdale, Arizona	United States
Heinen Obstectrics & Gynecology	Eunice, Louisiana	United States
Newlife Wellness OBGYN	Brooklyn, New York	United States
Lakeshore Women's Specialists	Mooresville, North Carolina	United States
Cincinnati Obgyn	Cincinnati, Ohio	United States
James D. Kasten, M.D., Inc.	Norwalk, Ohio	United States
Regional Obstetrical Consultants	Chattanooga, Tennessee	United States
Texas Maternal-Fetal Medicine	Webster, Texas	United States

+Investigators

Peter Stiegler, PhD, Study director, Head of Clinical Affairs