Clinical trial NCT06808880: EXpanding Prenatal Cell Free DNA Screening Across MoNogenic Disorders (EXPAND)
Official title: EXpanding Prenatal Cell Free DNA Screening Across MoNogenic Disorders (EXPAND)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Single Gene NIPT
Keywords: single gene NIPT
Lead sponsor: Natera, Inc.
Sponsor class: INDUSTRY
First posted: 2025-02-05
Enrollment: 4000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Natera sgNIPT is intended for use in pregnant people whose fetus/ fetuses are identified as at increased risk for a single gene disorder 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 a concern for single-gene disorder in the fetus/ fetuses irrespective of carrier status (e.g., based on fetal ultrasound findings).

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)

Eligibility criteria: 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

Primary outcomes:
measure: Performance of sgNIPT assay in the detection of primary four autosomal recessive disorders
timeFrame: Following the development of the sgNIPT assay, approximately 2 years after the launch of the study
Secondary outcomes:
measure: Performance of sgNIPT assay in the detection of single gene disorders other than the primary four
timeFrame: Following the development of the primary disorder assay, approximately 2.5 years after the launch of the study
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Valley Perinatal
state: Arizona
city: Los Angeles
country: United States
facility: Cedars Sinai Prenatal Diagnosis Center
state: California
city: Los Angeles
country: United States
facility: Center for Fetal Medicine and Womens Ultrasound
state: California
city: Sacramento
country: United States
facility: Pediatrix -Perinatal Associates of Sacramento
state: California
city: San Carlos
country: United States
facility: Natera Inc
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Orlando
country: United States
facility: Orlando Health Inc. (Winnie Palmer Hsopital)
state: Florida
city: Rockville
country: United States
facility: Maternal Fetal Medicine Associates of Maryland
state: Maryland
city: Jackson
country: United States
facility: UMMC WH Univerity Center For Fetal Medicine
state: Mississippi
city: Lawrenceville
country: United States
facility: Capital Health
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Robert Wood Johnson Medical School
state: New Jersey
city: New Hyde Park
country: United States
facility: Northwell (Northshore/LIJ)
state: New York
city: New York
country: United States
facility: NYU Langone
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Poughkeepsie
country: United States
facility: Lescale Maternal Fetal Medicine
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Austin
country: United States
facility: Austin Maternal Fetal Medicine/St. Davids Healthcare
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch (UTMB)
state: Texas
city: Stafford
country: United States
facility: PEDIATRIX Medical Services, Inc. Master + Houston
state: Texas
Study officials:
References: