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

NCT ID: NCT07261891

Last Updated: 2025-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-21

Study Completion Date

2030-12-01

Brief Summary

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

Detailed Description

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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.

Conditions

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Primary Immunodeficiency Diseases (PID)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

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

Group Type OTHER

blood sampling

Intervention Type 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

Healthy controls (without immune-mediated disease)

Group Type OTHER

blood sampling

Intervention Type 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.

Interventions

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blood sampling

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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Research Foundation - Flanders (Fonds Wetenschappelijk Onderzoek)

OTHER

Sponsor Role collaborator

prof. dr. Rik Schrijvers

OTHER

Sponsor Role lead

Responsible Party

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prof. dr. Rik Schrijvers

Prof. dr.

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Rik Schrijvers, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UZ Leuven

Locations

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University Hospitals Leuven,

Leuven, Vlaams-Brabant, Belgium

Site Status RECRUITING

Countries

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Belgium

Central Contacts

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Rik Schrijvers, MD, PhD

Role: CONTACT

+3216342985

Facility Contacts

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Cecilia Iglesias Herrero, MPharm

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 37020552 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33679782 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32582194 (View on PubMed)

Other Identifiers

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G054022N

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

S69751

Identifier Type: -

Identifier Source: org_study_id

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