Ex vivo testing of JAK inhibitors and a gene-therapy approach for JAK-STAT related immune disorders

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

This project will try JAK-inhibitor drugs and a gene-therapy approach on blood samples from adults with JAK-STAT pathway primary immunodeficiencies and healthy controls to see how immune cells and gene expression change.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Universitaire Ziekenhuizen KU Leuven (Academic / other)
• Locations: 1 site (Leuven, Vlaams-Brabant)
• Trial ID: NCT07261891 on ClinicalTrials.gov

What this trial studies

Researchers will take blood samples from adults with genetically confirmed or suspected JAK-STAT pathway disorders (including STAT1 gain-of-function) and from healthy controls and expose bulk and sorted immune cells ex vivo to different JAK inhibitors. They will measure pSTAT signaling, transcriptional profiles, and cytokine production after stimulation to see which cell types normalize and which remain refractory. The team will also test the technical feasibility of a gene-therapeutic correction strategy for STAT1 GOF in patient cells outside the body. Findings will be used to map treatment blind spots and inform whether specific JAK inhibitors or gene approaches warrant further clinical development.

Who should consider this trial

Good fit: Adults (18+) with genetically confirmed or highly suspected disorders causing exaggerated JAK-STAT signaling, such as STAT1 gain-of-function, as well as healthy volunteers for control samples, are the ideal candidates.

Not a fit: Children under 18, people unwilling to give consent, and patients whose disease is not driven by JAK-STAT hyperactivity are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the work could identify which JAK inhibitors most effectively normalize immune signaling and show whether a gene-therapy approach is technically feasible, guiding personalized treatment development.

How similar studies have performed: Clinical use of JAK inhibitors (e.g., ruxolitinib) has shown benefit in some STAT1 GOF patients, but ex vivo profiling and gene-therapy testing for this indication remain novel and less established.

Eligibility criteria

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

Where this trial is running

Leuven, Vlaams-Brabant

• University Hospitals Leuven, — Leuven, Vlaams-Brabant, Belgium (Recruiting)

Study contacts

• Principal investigator: Rik Schrijvers, MD, PhD — UZ Leuven
• Study coordinator: Rik Schrijvers, MD, PhD

Conditions Primary Immunodeficiency Diseases; JAK inhibitors; STAT1 gain-of-function; gene therapy