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NCT Number: NCT07261891

Ex Vivo Evaluation of JAK-inhibitor and Gene Therapeutical Approach in JAK-STAT Related Disorders

The investigators want to study the JAK-inhibitors and their impact on the immune system and evaluate the potential of a gene-therapeutic strategy

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Key information

Conditions

Primary Immunodeficiency Diseases (PID) Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Immune System Diseases Immunologic Deficiency Syndromes Primary Immunodeficiency Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University Hospitals Leuven,

Leuven, Vlaams-Brabant, 3000, Belgium

Location status: Recruiting

Location contact

Cecilia Iglesias Herrero, MPharm

CONTACT

[email protected]

About this study

The investigators want to study ex vivo the effect of JAK-inhibitors on the transcriptional profile and immune cell landscape in patients with inborn errors of the JAK-STAT pathway and the ex vivo evaluation of the feasibility of a gene therapeutic approach for STAT1 GOF. Following aspects will be compared:

  • To study pSTAT, transcriptional profile and cytokine production on bulk and sorted peripheral blood cell populations following stimulation in the presence or absence of different jakinibs
  • To evaluate to what extent jakinibs can normalize the transcriptional in different cell types (or not and identify blind spots of this treatment strategy)
  • To evaluate ex vivo the impact of a gene therapeutic approach for STAT1 GOF.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Cases (A): adult patients presenting with a genetically confirmed or highly suspected disorder leading to an exagerated JAK-STAT pathway.
  • Controls (B): participants eligible for inclusion in this study must fall in one of the following categories:
  • Healthy controls (without immune-mediated disease)

Exclusion criteria

  • Children (< 18 years at time of recruitment)
  • Persons unable or unwilling to give informed consent

Treatment and study plan

Blood sampling

Diagnostic Test

Blood/serum samples will be collected during routine clinical visits at the time of planned peripheral venous blood sampling. Samples will be processed and either used immediately (flow cytometry-based cell sorting, gDNA extraction, in vitro functional assays, primary cell culture or single-cell applications) or stored for later analysis.

Primary outcomes

  1. Change in STAT phosphorylation levels in peripheral blood mononuclear cells (PBMCs) after cytokine stimulation with and without JAK inhibitor exposure

    Time frame: From time of inclusion to 24 months

    Quantification via Median fluorescence intensity (MFI) of phosphorylated STAT1, STAT3, and STAT5 using multiparameter flow cytometry in bulk PBMCs and sorted T cells, B cells, NK cells, and monocyte subsets after standardized cytokine stimulation (e.g., IFNα, IFNγ, IL-6, IL-2) with or without JAK inhibitor exposure. Outcomes reported as fold-change relative to baseline.

  2. Change in transcriptional profiles of immune cell subsets during JAK inhibitor treatment

    Time frame: From time of inclusion to 24 months

    Differential gene expression assessed by single-cell RNA sequencing of PBMCs. Outcome is reported as the number of differentially expressed genes (adjusted p<0.05) at different sampling timepoints (n=3)

  3. Impact of ex vivo gene therapeutic correction in STAT1 gain-of-function patient-derived PBMCs

    Time frame: 24 months from inclusion

    On-target editing efficiency measured as percentage of corrected alleles by targeted sequencing.

Secondary outcomes

  1. Mutation-specific differences in response to JAK inhibitor treatment

    Time frame: From time of inclusion to 24 months

    Comparison of cytokine-induced phosphorylation (MFI of pSTAT1, pSTAT3, pSTAT5) and transcriptional responses (differential expression and pathway enrichment) between patients harboring distinct STAT1 gain-of-function variants. Outcomes reported as half-inhibitory concentration IC50 and area under the curve AUC in comparison to baseline

  2. Impact of our gene therapeutic approach on cell viability

    Time frame: From time of inclusion to 24 months

    Cell viability will be measured with MTT-assay

  3. Off target events in our ex vivo gene therapeutic approach

    Time frame: 24 months

    Off-target events detected by GUIDE-seq and confirmed by amplicon sequencing.

  4. Transcriptional correction of our ex vivo gene therapeutic approach

    Time frame: 24 months

    Transcriptional correction measured by single-cell RNA sequencing (fold-change of interferon pathway gene expression).

  5. Functional differentiation capacity of gene therapy-corrected cells

    Time frame: 24 months

    Functional differentiation capacity of corrected cells assessed by flow cytometry (percentages of T, B, NK, and monocyte subsets).

Study contacts

Contact information is provided by the study sponsor or research team.

Rik Schrijvers, MD, PhD

CONTACT

[email protected]

+3216342985

Sponsors and collaborators

Lead sponsor

prof. dr. Rik Schrijvers

Other

Collaborators

  • Research Foundation - Flanders (Fonds Wetenschappelijk Onderzoek)

Registry information

Official study title

Ex Vivo Evaluation of JAK-inhibitor and Gene Therapeutical Approach in JAK-STAT Related Disorders (JAKarta Study)

Acronym: JAKarta

Important dates

Study start
2024
Primary completion
2028
Study completion
2030
First posted
Dec 3, 2025
Registry last updated
Dec 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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