Study to Compare Traditional and Emerging Methods for Structural Variant Analysis in Prenatal, Postnatal, and Hematologic Samples

Multicenter Performance Study Using a Non-CE-marked in Vitro Diagnostic Medical Device (IVD) for the Standardization and Comparative Evaluation of Traditional and Emerging Methods for the Analysis of Structural Variants in Prenatal, Postnatal, and Oncohematological Samples

The study goal is to evaluate an innovative technology, KaryoSolver, which enables molecular karyotype reconstruction, in comparison with reference conventional methods, in terms of:

Presence or absence of clinically detectable structural variants; Type of alteration (aneuploidies, deletions, duplications); Copy number present. KaryoSolver is a software system for reconstructing the molecular karyotype from low-coverage genomic sequencing data using long-read technology.

The expected performance of the device under study is its ability to detect and classify the main clinically detectable structural variants within included samples in a manner consistent with the reference comparators, using a standardizable workflow, competitive turnaround times, and adequate reproducibility.

Study Overview

• Status: Recruiting
• Conditions: Aneuploidy; Chromosome Aberrations; Chromosome Duplication; Copy Number Variation; Chromosome Deletion; Abnormal Karyotype

Detailed Description

In particular, the study contributes to demonstrating the following requirements:

• scientific validity, through the correlation between Karyosolver and the aCGH/SNP array result used as a reference;
• analytical performance, including accuracy, analytical sensitivity, analytical specificity, and reproducibility of the method, evaluated according to the criteria defined by ISO 5725;
• clinical performance, through the evaluation of the test's ability to correctly identify copy number variations (CNVs) or regions of loss of heterozygosity (LOH/ROH) already reported in the samples selected for the study.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Giulia Fugazza, Clinical Project Manager; Phone Number: +41 (0) 91 224 70 81; Email: info@4bases.ch

Study Locations

• Italy
  • Florence, Italy, 50134
    • Recruiting
    • SOD Diagnostica Genetica Azienda Osepdaliero-Universitaria Careggi
    • Contact: Elisabetta Pelo, Medical Doctor; Email: infogenetica@aou-careggi.toscana.it
    • Principal Investigator: Elisabetta Pelo
  • Vicenza, Italy, 36100
    • Recruiting
    • UOSD Genetica Medica e Genomica Azienda ULSS8 Berica
    • Contact: Daniela Zuccarello, Medical Doctor; Phone Number: +39 0444-753360; Email: genetica@aulss8.veneto.it
    • Principal Investigator: Daniela Zuccarello, Medical Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The biological samples are residual samples already available at the two participating clinical centers. The samples originate from diagnostic workups that have already been completed and were not collected specifically for this study. In particular, residual samples related to prenatal, postnatal constitutional, and oncohematological diagnostics may be used, in accordance with the criteria set forth in the protocol.

Description

Inclusion Criteria:

1. Prenatal, postnatal, and oncohematological samples.
2. Availability of results obtained using at least one reference method.
3. Valid informed consent for use in research.
4. Sufficient quantity and quality of DNA for analysis.

Exclusion Criteria:

1. Absence of valid informed consent.
2. Incomplete documentation of reference results.
3. Insufficient or degraded DNA.

Study Plan

How is the study designed?

Design Details

• Observational Models: OTHER
• Time Perspectives: RETROSPECTIVE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall diagnostic concordance between KaryoSolver and reference methods for the identification of clinically detectable structural variants.	through study completion, an average of 1 year
Agreement on the presence/absence of clinically relevant chromosomal alterations between KaryoSolver and reference methods	through study completion, an average of 1 year
Agreement by category of identified alteration (aneuploidies, deletions, duplications) between KaryoSolver and reference methods	through study completion, an average of 1 year
Percentage of cases correctly classified by KaryoSolver compared to the reference comparator	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Intra-run reproducibility of KaryoSolver, assessed as the agreement of results obtained from replicates analyzed in the same session	through study completion, an average of 1 year
Inter-run reproducibility of KaryoSolver, assessed as the agreement of results obtained from replicates analyzed in different sessions	through study completion, an average of 1 year
Average analytical run time per sample with KaryoSolver compared to reference methods	through study completion, an average of 1 year
Average total reporting time/turnaround time with KaryoSolver compared to reference methods.	through study completion, an average of 1 year
Reduction in technical/interpretive workload, assessed in terms of man-hours or the number of manual tasks required	through study completion, an average of 1 year
Average cost per sample analyzed with KaryoSolver compared to reference methods	through study completion, an average of 1 year
Proportion of cases potentially eligible for faster diagnosis using KaryoSolver compared to the standard workflow	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: 4bases Italia Srl

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: October 12, 2026
• First Submitted That Met QC Criteria: November 5, 2026
• First Posted (Actual): November 12, 2026

Study Record Updates

• Last Update Posted (Actual): November 12, 2026
• Last Update Submitted That Met QC Criteria: November 5, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: Diagnostic accuracy; Molecular cytogenetics; Genome-wide chromosomal analysis; Oxford Nanopore sequencing; Genetic Analysis Software
• Additional Relevant MeSH Terms: Pathologic Processes; Monosomy; Pathological Conditions, Signs and Symptoms; Chromosome Deletion; Chromosome Aberrations; Aneuploidy; Chromosome Duplication; Abnormal Karyotype
• Other Study ID Numbers: KaryoSolver-ONT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

IPD will not be shared because this is a non-interventional study which does not produce any health outcomes; it is, in fact, a performance study involving IVDs conducted solely for methodological research purposes, with no results being reported for diagnostic or therapeutic purposes.

Drug and device information, study documents

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