Expanded Noninvasive Genomic Medical Assessment: The Enigma Study

Down Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02787486
• Other study ID #: PRO-102-ENIGMA
• Status: Completed
• Start date: October 2015
• Est. completion date: September 2018

Study information

• Verified date: January 2019
• Source: Progenity, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 760
• Est. completion date: September 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 54 Years

Eligibility

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

Related Conditions & MeSH terms

• Aneuploidy
• Chromosome Deletion
• DiGeorge Syndrome
• Down Syndrome
• Edwards Syndrome
• Klinefelter Syndrome
• Patau Syndrome
• Syndrome
• Turner Syndrome

Intervention

Other:
• Blood sampling for Laboratory Developed Test (LDT) analysis
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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Progenity, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Primary Objective	about 3 years
Secondary	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