Newborn Genomic Sequencing Pilot Study

Newborn Genomic Sequencing (BeginNGS) Prospective Pilot Study

The goal of this clinical trial is to test a new method for newborn screening using whole genome sequencing, called BeginNGS. Newborns who are not suspected of having genetic diseases and who are admitted to the NICU at Rady Children's Hospital, San Diego, will be enrolled. The main questions this study aims to answer are:

• What is the diagnostic yield of diagnostic whole genome sequencing (DWGS) in this population?
• What is the diagnostic sensitivity and specificity of BeginNGS and whole exome sequencing (WES) as compared to DWGS?
• What are the potential issues related to implementing DWGS in this population?

Enrolled newborns will have a blood sample taken and will receive three tests:

• DWGS
• BeginNGS
• WES

Study Overview

• Status: Active, not recruiting
• Conditions: Genetic Disease
• Intervention / Treatment: Genetic: Whole genome sequencing; Genetic: BeginNGS test; Genetic: WES

Detailed Description

Newborn screening (NBS) by testing dried blood spots (DBS) identifies newborns with a few diseases for which effective treatments are available to enable treatment at or before symptom onset. Because NBS improves outcomes in these diseases, it is performed on almost all US babies. The current Federal recommended NBS list is limited to 35 conditions and identifies ~6,600 affected children per year. In genetic diseases not screened by NBS, however, outcomes remain poor because of delays in diagnosis and treatment. The investigators recently developed a system for NBS for 434 severe, childhood genetic diseases for which effective treatments are available using whole genome sequencing (WGS), called BeginNGS. Retrospective studies showed BeginNGS to have a true negative rate (specificity) of 99.7% and true positive rate (sensitivity) of 88.8%. The investigators now propose to undertake a first prospective study in newborns admitted to the Neonatal Intensive Care Unit (NICU) at Rady Children's Hospital, San Diego (RCHSD) to compare the sensitivity and specificity of BeginNGS with that of standard, diagnostic rapid whole genome sequencing (DWGS) and whole exome sequencing (WES). This study is in preparation for larger, future clinical trials.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lauren Olsen, MSN; Phone Number: 228456 858-576-1700; Email: lolsen1@rchsd.org

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Rady Children's Hospital San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Neonates less than or equal to 10 days old who are admitted to the RCHSD NICU.

Exclusion Criteria:

1. Neonates who have enrolled in another clinical study at Rady Children's Institute for Genomic Medicine or in whom DWGS has been ordered or is being considered.
2. Neonates whose mother is less than 18 years of age.
3. Neonates who are wards of the state.
4. Neonates whose parent/legal guardian is unable to provide consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enrollees; Enrolled infants will receive 3 tests (DWGS, BeginNGS, and WES). DWGS will be performed in a standard manner. BeginNGS and WES will be performed in a batch after completion of enrollment. The diagnostic sensitivity and specificity of BeginNGS and WES will be compared to DWGS (a standard clinical test compliant with the Clinical Laboratory Improvement Amendments Act).	Genetic: Whole genome sequencing; Standard diagnostic whole genome sequencing will be performed.; Genetic: BeginNGS test; Genomic sequencing that screens for 434 genetic diseases.; Genetic: WES; Whole exome sequencing will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of enrolled infants who are diagnosed with a genetic disease by DWGS.	Proportion	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of enrolled infants who are identified with a genetic disease by BeginNGS.	Proportion	18 months
Proportion of enrolled infants who are identified with a genetic disease by WES.	Proportion	18 months
Proportion of enrolled infants who have a positive standard NBS test.	Proportion	18 months
Proportion of parents approached who agree to participate in the study.	Proportion	18 months
Parental reasons for refusal.	Questionnaire	18 months
Time from sample arriving in lab to return of DWGS results.	Time (days)	18 months
Time from birth to return of DWGS results.	Time (days)	18 months
Results of confirmatory testing if BeginNGS or WES identifies a diagnostic finding not reported by DWGS.	Proportion of findings confirmed	18 months

Collaborators and Investigators

• Sponsor: Rady Pediatric Genomics & Systems Medicine Institute
• Investigators: Principal Investigator: Stephen Kingsmore, MD DSc, Rady Children's Institute for Genomic Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2023
• Primary Completion (Actual): February 28, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: February 16, 2024
• First Submitted That Met QC Criteria: February 16, 2024
• First Posted (Actual): February 26, 2024

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn
• Other Study ID Numbers: 20226892

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No