Primary Immunodeficiency Diseases (PID)JAKartaNCT07261891
Ex Vivo Evaluation of JAK-inhibitor and Gene Therapeutical Approach in JAK-STAT Related Disorders
A study testing blood sampling in people with Primary Immunodeficiency Diseases (PID), run by prof. dr. Rik Schrijvers at 1 site in Belgium.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Primary Immunodeficiency Diseases (PID)
- What is being tested?
- blood sampling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteBelgium
- Study dates
- 21 Nov 2024to 1 Dec 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- Children (< 18 years at time of recruitment)
- Persons unable or unwilling to give informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Belgium1 site, 1 recruiting
- Recruiting
University Hospitals Leuven,
Leuven, Vlaams-Brabant, 3000
Cecilia Iglesias Herrero, MPharm, cecilia.iglesiasherrero@kuleuven.be
About this study
Official title: Ex Vivo Evaluation of JAK-inhibitor and Gene Therapeutical Approach in JAK-STAT Related Disorders (JAKarta Study)
The investigators want to study the JAK-inhibitors and their impact on the immune system and evaluate the potential of a gene-therapeutic strategy
Read the 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.
- Conditions
- Primary Immunodeficiency Diseases (PID)
- Being tested
- blood sampling
- Keywords
- JAK inhibitors, STAT1 gain-of-function, gene therapy
- Medical subject headings
- Primary Immunodeficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood samplingDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: blood sampling |
| Healthy controls | Other | Healthy controls (without immune-mediated disease) Receives: Diagnostic Test: blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: 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.
Measured: 24 months from inclusion
Secondary outcomes (5)
Mutation-specific differences in response to JAK inhibitor treatment
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
Measured: From time of inclusion to 24 months
Impact of our gene therapeutic approach on cell viability
Cell viability will be measured with MTT-assay
Measured: From time of inclusion to 24 months
Off target events in our ex vivo gene therapeutic approach
Off-target events detected by GUIDE-seq and confirmed by amplicon sequencing.
Measured: 24 months
Transcriptional correction of our ex vivo gene therapeutic approach
Transcriptional correction measured by single-cell RNA sequencing (fold-change of interferon pathway gene expression).
Measured: 24 months
Functional differentiation capacity of gene therapy-corrected cells
Functional differentiation capacity of corrected cells assessed by flow cytometry (percentages of T, B, NK, and monocyte subsets).
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2025
- Study start21 Nov 2024
- Primary completion1 Dec 2028 (estimated)
- Study completion1 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Primary Immunodeficiency Diseases (PID)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- prof. dr. Rik Schrijvers
- Sponsor type
- University, hospital or other
- Collaborators
- Research Foundation - Flanders (Fonds Wetenschappelijk Onderzoek)
- Responsible party
- Sponsor-investigator, prof. dr. Rik Schrijvers, Universitaire Ziekenhuizen KU Leuven
- Investigators
- Rik Schrijvers, MD, PhD, Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07261891
- Sponsor's protocol ID
- S69751
- Other IDs
- G054022N
- Acronym
- JAKarta
- Status last verified
- Nov 2025
- First submitted
- 25 Jun 2025
- Last updated
- 3 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 37020552Giovannozzi 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.
PubMed 33679782Giovannozzi 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.
PubMed 32582194
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ex Vivo Evaluation of JAK-inhibitor and Gene Therapeutical Approach in JAK-STAT Related Disorders (JAKarta Study)
- ClinicalTrials.gov ID
- NCT07261891
- Acronym / sponsor ID
- JAKarta / S69751
- Conditions
- Primary Immunodeficiency Diseases (PID)
- Keywords
- JAK inhibitors, STAT1 gain-of-function, gene therapy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- prof. dr. Rik SchrijversUniversity, hospital or other
- Collaborators
- Research Foundation - Flanders (Fonds Wetenschappelijk Onderzoek)
- Study start
- 21 Nov 2024 (actual)
- Primary completion
- 1 Dec 2028 (estimated)
- Study completion
- 1 Dec 2030 (estimated)
- First posted
- 3 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Patients with a monogenic IEI with an hyperactive JAK-STAT pathway | Other | Diagnostic Test: blood samplingAdult patients presenting with a genetically confirmed or highly suspected disorder leading to an exagerated JAK-STAT pathway. |
| Healthy controls | Other | Diagnostic Test: blood samplingHealthy controls (without immune-mediated disease) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (2 listed)
- Children (< 18 years at time of recruitment)
- Persons unable or unwilling to give informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood samplingBlood/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. | Diagnostic test | Healthy controls, Patients with a monogenic IEI with an hyperactive JAK-STAT pathway |
Primary outcome
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.
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)
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.
5 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2025.
- Background: PubMed 37020552Staels 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.
- Background: PubMed 33679782Giovannozzi 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.
- Background: PubMed 32582194Giovannozzi 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Rik Schrijvers, MD, PhD principal investigator
UZ Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing blood sampling in people with Primary Immunodeficiency Diseases (PID), run by prof. dr. Rik Schrijvers at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rik Schrijvers, MD, PhD (+3216342985, rik.schrijvers@uzleuven.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07261891, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2025.