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

NCT07261891 | Recruiting

• 2 other identifiers: S69751G054022N
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Primary Immunodeficiency Diseases (PID)

Keywords

JAK inhibitors; STAT1 gain-of-function; gene therapy

Outcome Measures

Primary Outcomes (3)

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

  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.

  From time of inclusion to 24 months

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

  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)

  From time of inclusion to 24 months

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

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

  24 months from inclusion

Secondary Outcomes (5)

• Mutation-specific differences in response to JAK inhibitor treatment

  From time of inclusion to 24 months

• Impact of our gene therapeutic approach on cell viability

  From time of inclusion to 24 months

• Off target events in our ex vivo gene therapeutic approach

  24 months

• Transcriptional correction of our ex vivo gene therapeutic approach

  24 months

• Functional differentiation capacity of gene therapy-corrected cells

  24 months

Study Arms (2)

Patients with a monogenic IEI with an hyperactive JAK-STAT pathway

OTHER

Adult patients presenting with a genetically confirmed or highly suspected disorder leading to an exagerated JAK-STAT pathway.

Diagnostic Test: blood sampling

Healthy controls

OTHER

Healthy controls (without immune-mediated disease)

Diagnostic Test: blood sampling

Interventions

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.

Healthy controls; Patients with a monogenic IEI with an hyperactive JAK-STAT pathway

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cases (A): adult patients presenting with a genetically confirmed or highly suspected disorder leading to an exagerated JAK-STAT pathway.
• Healthy controls (without immune-mediated disease)

You may not qualify if:

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

Sponsors & Collaborators

• prof. dr. Rik Schrijvers: lead
• Research Foundation - Flanders (Fonds Wetenschappelijk Onderzoek): collaborator

Study Sites (1)

University Hospitals Leuven,

Leuven, Vlaams-Brabant, 3000, Belgium

RECRUITING

Related Publications (3)

• Staels F, Roosens W, Giovannozzi S, Moens L, Bogaert J, Iglesias-Herrero C, Gijsbers R, Bossuyt X, Frans G, Liston A, Humblet-Baron S, Meyts I, Van Aelst L, Schrijvers R. Case report: Myocarditis in congenital STAT1 gain-of function. Front Immunol. 2023 Mar 20;14:1095595. doi: 10.3389/fimmu.2023.1095595. eCollection 2023.

  PMID: 37020552 BACKGROUND

• Giovannozzi S, Demeulemeester J, Schrijvers R, Gijsbers R. Transcriptional Profiling of STAT1 Gain-of-Function Reveals Common and Mutation-Specific Fingerprints. Front Immunol. 2021 Feb 17;12:632997. doi: 10.3389/fimmu.2021.632997. eCollection 2021.

  PMID: 33679782 BACKGROUND

• Giovannozzi S, Lemmens V, Hendrix J, Gijsbers R, Schrijvers R. Live Cell Imaging Demonstrates Multiple Routes Toward a STAT1 Gain-of-Function Phenotype. Front Immunol. 2020 Jun 9;11:1114. doi: 10.3389/fimmu.2020.01114. eCollection 2020.

  PMID: 32582194 BACKGROUND

MeSH Terms

Conditions

Primary Immunodeficiency Diseases

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Rik Schrijvers, MD, PhD

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rik Schrijvers, MD, PhD

CONTACT

+3216342985; rik.schrijvers@uzleuven.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. dr.

Model Details: This is a parallel assignment study with two arms: (1) patients diagnosed with \[rare disease\] who will receive \[describe treatment\] and have blood drawn at specific time points, and (2) healthy controls who will undergo matched blood sampling for comparative analysis. Healthy controls will not receive the intervention.

Study Record Dates

• First Submitted: June 25, 2025
• First Posted: December 3, 2025
• Study Start: November 21, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)