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Recruiting NCT07261891

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

No phase Interventional Primary Immunodeficiency Diseases (PID)

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: blood sampling.
Who it may be relevant to
Registry conditions: Primary Immunodeficiency Diseases (PID). Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Belgium
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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

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.

Interventions

  • Diagnostic test 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.

Primary outcome measures

  • 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]
  • Change in transcriptional profiles of immune cell subsets during JAK inhibitor treatment [Time frame: From time of inclusion to 24 months]
  • Impact of ex vivo gene therapeutic correction in STAT1 gain-of-function patient-derived PBMCs [Time frame: 24 months from inclusion]
Secondary outcome measures (5)
  • Mutation-specific differences in response to JAK inhibitor treatment [Time frame: From time of inclusion to 24 months]
  • Impact of our gene therapeutic approach on cell viability [Time frame: From time of inclusion to 24 months]
  • Off target events in our ex vivo gene therapeutic approach [Time frame: 24 months]
  • Transcriptional correction of our ex vivo gene therapeutic approach [Time frame: 24 months]
  • Functional differentiation capacity of gene therapy-corrected cells [Time frame: 24 months]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation
Non-randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

Belgium · 1 center
  • University Hospitals Leuven, — Leuven

Publications

  • 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
  • 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
  • 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

Identifiers

NCT: NCT07261891 · S69751 · G054022N

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗