EXpanding Prenatal Cell Free DNA Screening Across MoNogenic Disorders (EXPAND)

Recruiting

• Conditions: Single Gene NIPT

• Registration Number: NCT06808880
• Lead Sponsor: Natera, Inc.

Brief Summary

The purpose of this research is to develop and validate a single gene Non-Invasive Prenatal Test. The development of this investigational single-gene noninvasive prenatal testing (sgNIPT) for conditions such as cystic fibrosis (CF), spinal muscular atrophy (SMA), Sickle cell disease, alpha thalassemia (a-thalassemia) and beta thalassemia (b-thalassemia) could provide information about the possibility that a child will be born with a serious health condition, in some cases in the absence of reproductive partner screening.

In order to develop a test for this purpose, investigators will collect blood samples and medical information from pregnant women who have pregnancies at higher risk for single gene disorders, such as those who are carriers for these conditions or affected by these conditions themselves, medical data from their reproductive partners in some cases, and either genetic testing results or a cheek swab sample from the newborn(s).

Detailed Description

Natera sgNIPT is intended for use in pregnant people whose fetus/ fetuses are identified as at increased risk for a single gene disorder, such as one of the disorders below, when there is no reproductive partner (paternal) screening available or when there is positive reproductive partner screening, but prenatal diagnostic testing is not an option or when there is concern for a single-gene disorder in the fetus/ fetuses irrespective of carrier status (e.g., based on fetal ultrasound findings). Disorders include:

CF (CFTR) SMA (SMN1) Alpha-thalassemia (HBA1/HBA2) Beta-hemoglobinopathies including sickle cell disease (HBB)

Study Timeline

• Study Start: 2024-01-25
• Study First Submitted: 2025-01-21
• Study First Submitted QC: 2025-01-29
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-17
• Study First Posted: 2025-03-25
• Last Update Posted: 2025-03-25
• Primary Completion: 2025-11
• Study Completion: 2026-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 4000

Inclusion Criteria

1. Age 18 or older at the time of informed consent

2. Maternal participant: Pregnant and blood draw at ≥ 9 weeks gestational age (GA)

3. Maternal participant is positive for a single-gene disorder and/or there are prenatal ultrasound findings suggestive for a fetal single-gene disorder, including but not limited to the genes listed in the primary and secondary objectives

4. Meet the criteria for one of the following:

   • Both maternal and reproductive partner (paternal) status are positive for the same single-gene disorder OR
   • A commercially available single-gene NIPT has been performed as part of clinical care and is reported as increased risk for an affected fetus/fetuses OR Maternal status is positive for one or more single-gene disorders and reproductive partner status is unknown OR
   • Prenatal ultrasound findings are suggestive of a fetal single-gene disorder (autosomal dominant, autosomal recessive, or X-linked condition) and enrollment is approved by the medical monitor.

5. Willing to permit release of neonatal health information and the performance of a newborn cheek swab within 6 months following delivery

6. Willing to sign informed consent and comply with study procedures

Exclusion Criteria

1. Reproductive partner found to not be positive for the same autosomal recessive genetic disorder as the pregnant maternal carrier, or vice versa
2. Surrogate gestation or egg donor pregnancy
3. Negative preimplantation genetic testing for the single-gene disorder identified in one or both parents

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Performance of sgNIPT assay in the detection of primary four autosomal recessive disorders	Following the development of the sgNIPT assay, approximately 2 years after the launch of the study	The sgNIPT assay call, high risk or low risk; will be compared to the genetic outcome of the fetus/ fetuses Affected; or Not Affected; as determined by prenatal genetic testing, post-natal genetic testing or genetic testing performed on the newborn cheek swab sample. Sensitivity, PPV, NPV, and no call rates will be assessed.

Secondary Outcome Measures

Name	Time	Method
Performance of sgNIPT assay in the detection of single gene disorders other than the primary four	Following the development of the primary disorder assay, approximately 2.5 years after the launch of the study	The sgNIPT assay call, high risk or low risk; will be compared to the genetic outcome of the fetus/ fetuses Affected; or Not Affected; as determined by prenatal genetic testing, post-natal genetic testing or genetic testing performed on the newborn cheek swab sample. Sensitivity and PPV pooled across single gene disorders other than the four primary disorders

Trial Locations

Locations (20)

Valley Perinatal; 🇺🇸 Glendale, Arizona, United States

Cedars Sinai Prenatal Diagnosis Center; 🇺🇸 Los Angeles, California, United States

Center for Fetal Medicine and Womens Ultrasound; 🇺🇸 Los Angeles, California, United States

Pediatrix -Perinatal Associates of Sacramento; 🇺🇸 Sacramento, California, United States

Natera Inc; 🇺🇸 San Carlos, California, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Orlando Health Inc. (Winnie Palmer Hsopital); 🇺🇸 Orlando, Florida, United States

Maternal Fetal Medicine Associates of Maryland; 🇺🇸 Rockville, Maryland, United States

UMMC WH Univerity Center For Fetal Medicine; 🇺🇸 Jackson, Mississippi, United States

Capital Health; 🇺🇸 Lawrenceville, New Jersey, United States

Rutgers Robert Wood Johnson Medical School; 🇺🇸 New Brunswick, New Jersey, United States

Northwell (Northshore/LIJ); 🇺🇸 New Hyde Park, New York, United States

NYU Langone; 🇺🇸 New York, New York, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Weill Medical College of Cornell University; 🇺🇸 New York, New York, United States

Lescale Maternal Fetal Medicine; 🇺🇸 Poughkeepsie, New York, United States

University of Rochester; 🇺🇸 Rochester, New York, United States

Austin Maternal Fetal Medicine/St. Davids Healthcare; 🇺🇸 Austin, Texas, United States

University of Texas Medical Branch (UTMB); 🇺🇸 Galveston, Texas, United States

PEDIATRIX Medical Services, Inc. Master + Houston; 🇺🇸 Stafford, Texas, United States