Clinical trial NCT06875089: A Pilot Study to Assess the Feasibility and Acceptability of Newborn Screening Using in Silico Panel-based Solo Genome Sequencing in France
Official title: A Pilot Study to Assess the Feasibility and Acceptability of Newborn Screening Using in Silico Panel-based Solo Genome Sequencing in France PERIGENOMED-CLINICS 1 (PGC1 Study)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Newborn Screening Programmes for Rare Diseases
Lead sponsor: Centre Hospitalier Universitaire Dijon
Sponsor class: OTHER
First posted: 2025-03-13
Enrollment: 5000
Sex: ALL
Minimum age (years): 0
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: all the parents of live newborns in each participating maternity unit

Brief summary: Newborn Screening (NBS) based on genome sequencing (GS) is currently the subject of particular attention at both European and international levels. Over the past three years, several publications have discussed the opportunities and challenges of using GS for NBS. To date, only two Chinese programs have published their results, the first on a series of 29,601 healthy newborns and the second on a series of 10,334 healthy newborns and 668 high-risk infants. Globally, more than twenty pilot projects are underway, although none has been initiated within the French context thus far. Across the different pilot projects, various study designs are used. Most have opted for a targeted GS-based analysis to screen for pediatric-onset diseases. Some projects focus solely on diseases for which effective drugs or interventions exist to prevent or reduce symptoms. In contrast, others offer parents the option to screen their newborns for diseases without current treatment options, but for which a treatment is underdevelopment, or with interest in early management, a choice exercised by most parents. Indeed, early diagnosis of these diseases can help to introduce treatments or interventions when they become available, to participate in research trials on new treatments and to receive early management and genetic counseling.

In France, the national NBS program has long been recognized worldwide for its organizational quality and comprehensiveness, although, until recently, it has one of the lowest numbers of diseases screened in Europe. As of mid-2024, the French NBS only includes 14 serious diseases. Recently, the French bioethics law has evolved to allow the use of genetic testing as a first-line procedure for NBS. At the same time, the development and efficiency of genomic techniques and the rapid increase in the number of treatable rare diseases (RDs) raise questions about the acceptability and relevance of these genomic methods for NBS and its possible extension. The extension of NBS to many RDs of early onset represents a real public health challenge as RDs, 80% of which are of genetic origin, account for 10% of deaths before the age of 5.

The FHU TRANSLAD has elaborated the PERIGENOMED Project, a large-scale project which aims to assess the relevance of pGS-NBS in France (analytical and clinical validity, clinical utility and psychosocial, ethical and organizational issues).

The pGS-NBS (also known as in silico panel-based GS, i.e. an analysis carried out entirely using informatic tools) consists of bioinformatics filtering steps that return only selected variants and/or rare variants from targeted genes issued from GS. So, even if the source data comes from the GS, it is possible to configure the pipeline to return only those variations known to be responsible for specific RDs.

the PERIGENOMED Project will be led in two steps. The first pilot step (PERIGENOMED-CLINICS 1 - PGC1 Study), presented in this protocol, aims to evaluate the feasibility and acceptability of pGS-NBS France. This pilot study plans to screen 2,500 newborns using pGS-NBS targeting two lists of genes (1 corresponding to genes variables responsible of treatable rare diseases, 2 including genes variation leading to actionable rare diseases). In both lists only RDs of early onset are considered. PGC1 study will be carried in 5 healthcare centers in France, with results expected to be returned to clinicians within less than 4 weeks. It will also provide an understanding of the optimal information and analytical pathways, and the possible organizational repercussions of pGS-NBS as well as a first insight about the validity of the pGS-NBS and about the clinical course of newborns screened positive and with a confirmed RD Two studies in humanities and social sciences (HSS) will also be linked to PGC1 Study. The first will focus on the reasons given by decliners and on the medical and socio-economic characteristics (at the individual and contextual level) of decliners versus participants. The second will assess the psychosocial impact of result disclosure on families of positive newborns, comparatively of negative ones.

These initial results will provide the first outcomes before the launch of a second larger phase PERIGENOMED-CLINICS 2 (PGC2 Study - 22,000 newborns), designed for studying the implementation of such pGS-NBS in routine on a regional level.


Eligibility criteria: Inclusion Criteria:

For satisfaction study about the information \& identification of determinants of acceptability :

Inclusion criteria for parents/legal guardians :

* All future parents approached for whom the unborn child will be cared for in the participating maternity unit
* At least one parent/legal guardian who physically received information about the study
* Future parents/legal guardian who do not object to the use of their data
* Parent(s) or legal guardian(s) affiliated to a social security system or beneficiaries of such a system

For pGS-NBS :

Inclusion criteria for newborn :

* All babies born in one of the participating centers
* Newborn who are less than 28 days at the date of the collection of PGC1 blotting paper

Inclusion criteria for parents/legal guardians

* At least one biological parent who physically received information about the study
* Parent(s) or legal guardian(s) who do not object to "conventional" NBS
* At least one parent/legal guardian able to provide consent for testing the infant
* Informed consent signed by at least one parent/legal guardian
* Agreement of the second parent/legal guardian for testing the infant (unless he is unknown or loss of contact) obtained from the first parent/legal guardian if his written informed consent has not been obtained
* Parent(s) or legal guardian(s) affiliated to a social security system or beneficiaries of such a system

Exclusion Criteria:

Non inclusion criteria for satisfaction studies and pGS-NBS :

Non-inclusion criteria for parents/legal guardians :

- Parent(s) or legal guardian(s) under legal protection (guardianship, tutorship) or to a court order

Primary outcomes:
measure: parents who have accepted the pGS-NBS for their children for Treatable list
timeFrame: until 2 days after birth with extension up to 28 days in case of hospitalization in intensive care
measure: results concerning the Treatable list returned to clinicians within 4 weeks following the sample
timeFrame: 4 weeks following the sample
Secondary outcomes:
measure: parents who have accepted the pGS-NBS for their children for Actionable list
timeFrame: until 2 days after birth
measure: results concerning the Actionable list returned to clinicians within 4 weeks following the sample,
timeFrame: 4 weeks following the sample
measure: Questionnaire for parents' satisfaction with the screening and reporting processes
timeFrame: up to 4 weeks
measure: profiles of parents who take part or not to pGS-NBS
timeFrame: at the baseline
measure: quantitative exploration
timeFrame: At : 1,6,12,24,36,48 and 60 months after positive results delivery At : 1 and 12 months after negative results delivery
measure: pGS-NBS performance
timeFrame: 5 years;
measure: Clinical evoluation of newborns with true positive results until 5 years
timeFrame: 5 years
measure: pGS-NBS performance
timeFrame: 3 months post pGS-NBS results delivery
measure: pGS-NBS performance
timeFrame: frame 1 month after the birth
measure: qualitative exploration
timeFrame: At : 1,6,12,24,36,48 and 60 months after positive results delivery At : 1 and 12 months after negative results delivery
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU d'Angers
city: Besançon
country: France
facility: CHU Besançon
city: Dijon
country: France
facility: CHU Dijon Bourgogne
city: Nantes
country: France
facility: CHU Hôtel Dieu
city: Rennes
country: France
facility: CHU Rennes - Hôpital Sud
Study officials:
References: