Aicardi-Goutières Syndrome (AGS)NCT06898372
Evaluate the Efficacy of Anti-Jak1 Inhibitors as Treatment for Patients With Aicardi-Goutières Syndrome
An observational study of Aicardi-Goutières Syndrome (AGS), run by IRCCS Fondazione Stella Maris at 1 site in Italy.
Trial summary
Aicardi-Goutières Syndrome (AGS) is a hereditary multisystem autoinflammatory disorder that predominantly affects the central nervous system. It is characterized by severe neurological disability and chronic inflammation caused by the persistent overproduction of type I interferon. Read more about this study
- Who is it for?
- Ages 0 to 25 years
- Conditions the study is for
- Aicardi-Goutières Syndrome (AGS)
- What is being tested?
- JAK Inhibitor
- How many people
- 24 participants
- Where
- 1 siteItaly
- Study dates
- 7 Apr 2024to 18 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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 0 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: A total of approximately 24 patients with Aicardi-Goutières Syndrome or AGS-related interferonopathies are expected to be enrolled, including 12 patients treated with different Janus Kinase 1/2 (JAK1/2) inhibitors, such as Baricitinib and Ruxolitinib, and 12 untreated patients, from the 9 Italian clinical centers involved in the study.
Who may be able to join
- Patients aged 0 to 25 years
- Patients who have been genetically diagnosed with Aicardi-Goutières Syndrome (AGS) or AGS-related interferonopathies For case cohort-Patients treated with Janus Kinase 1/2 (JAK1/2) inhibitors, such as Baricitinib or Ruxolitinib
Who cannot join
- Patients over the age of 25 years
- Patients who have not been genetically diagnosed with Aicardi-Goutières Syndrome (AGS) or AGS-related interferonopathies.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Multicenter Retrospective Observational Study to Evaluate the Efficacy of Anti-Jak1 Inhibitors as Treatment for Patients With Aicardi-Goutières Syndrome
Aicardi-Goutières Syndrome (AGS) is a hereditary multisystem autoinflammatory disorder that predominantly affects the central nervous system. It is characterized by severe neurological disability and chronic inflammation caused by the persistent overproduction of type I interferon. To date, nine causative genes of AGS have been identified, each of which can lead to classic AGS presentations, atypical forms, or other manifestations that do not meet the formal diagnostic criteria for AGS and are referred to as "AGS-related interferonopathies." Janus Kinase 1 (JAK1) inhibitors, including Baricitinib and Ruxolitinib, offer a promising therapeutic strategy for Aicardi-Goutières Syndrome (AGS) by directly targeting the central pathogenic pathway of the disease.
Patients treated with JAK1 inhibitors for AGS have shown significant improvement in systemic symptoms, though the effect on neurological symptoms and brain imaging remains unclear.
Read more
The aim of this project is to retrospectively analyze the efficacy, particularly on neurological symptoms and brain imaging, and the safety of JAK1 inhibitor treatment in AGS patients treated at Italian tertiary centers. Data will be collected before starting the therapy and during follow-up at 6, 12, 18, and 24 months, where available.
Preliminary data collection was carried out through a survey conducted by the AGS Italy group to assess the number of patients treated with JAK1 inhibitors.
Clinical, brain imaging, genetic, and laboratory data routinely recorded in nine different Italian centers as part of the standard clinical care of these patients will be retrospectively collected and analyzed.
In the second phase of the study, brain MRI data from AGS patients treated with JAK1 inhibitors will be compared to untreated AGS patients matched for age and genotype, in order to evaluate the potential therapeutic efficacy of JAK1 inhibitors on brain imaging compared to the natural clinical progression of the disease.
Through the analysis of the Italian experience, this study could lay the groundwork for drafting a potential consensus on the use of JAK1 inhibitors for the treatment of AGS patients.
- Conditions
- Aicardi-Goutières Syndrome (AGS)
- Being tested
- JAK Inhibitor
- Keywords
- Anti-Jak1/2, Ruxolitinib, Baricitinib, AGS-related interferonopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JAK InhibitorDrug
The retrospective analysis will examine the effects of Janus Kinase 1/2 (JAK1/2) inhibitors, such as Baricitinib and Ruxolitinib, on neurological symptoms and brain MRI.
| Study group | Role | What they receive |
|---|---|---|
| Patients with AAGS or AGS-related interferonopathies treated with Anti-Jak1/2 | Study group:
1. Patients aged 0 to 25 years
2. Genetic diagnosis of Aicardi-Goutières Syndrome or AGS-related interferonopathies
3. Treatment with Janus Kinase 1/2 (JAK1/2) inhibitors, including Baricitinib and Ruxolitinib Receives: Drug: JAK Inhibitor | |
| Patients with AGS or AGS-related interferonopathies not treated with Anti-Jak1/2 | Control group: 1. Patients aged 0 to 25 years matched with the study cases 2. Genetic diagnosis of Aicardi-Goutières Syndrome or AGS-related interferonopathies with genotype matched to the study cases 3. Not treated with Janus Kinase 1/2 (JAK1/2) inhibitors, such as Baricitinib and Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of JAK-1/2 inhibitor therapy on Clinical criteria (AGS scale)
Evaluate the efficacy of JAK-1/2 inhibitor therapy through clinical criteria (AGS scale) in all patients with Aicardi-Goutières Syndrome or AGS-related interferonopathies, highlighting potential differences in efficacy between the different genotypes. The Aicardi-Goutières Syndrome (AGS) Severity Scale is a clinical tool used to assess the severity of neurological impairment in individuals with AGS. The scale ranges from 0 to 11, with higher scores indicating better neurological function.
Measured: After 6, 12, 18, and 24 months of treatment, if the data is available.
Efficacy of JAK-1/2 inhibitor therapy on laboratory parameter (IFN signature)
Evaluate the efficacy of JAK-1/2 inhibitor therapy through IFN signature (IFN score) on blood in all patients with Aicardi-Goutières Syndrome or AGS-related interferonopathies, highlighting potential differences in efficacy between the different genotypes. The IFN Score is typically expressed as a fold change relative to healthy controls or as a normalized relative value, measuring the expression of interferon-stimulated genes (ISGs). In patients with pathological activation of the interferon pathway, the IFN Score ranges from 0 to >10-15, indicating significant ISG upregulation. While the pathological cut-off varies across studies, an IFN Score >2-3 is often considered indicative of abnormal interferon pathway activation.
Measured: After 6, 12, 18, and 24 months of treatment, if the data is available.
Efficacy of JAK-1/2 inhibitor therapy on instrumental parameters (brain MRI)
Evaluate the efficacy of JAK-1/2 inhibitor therapy through brain MRI (Improved/Unchanged/Worsening) in all patients with Aicardi-Goutières Syndrome or AGS-related interferonopathies, highlighting potential differences in efficacy between the different genotypes.
Measured: After 6, 12, 18, and 24 months of treatment, if the data is available.
Evaluate the side effects of JAK-1/2 inhibitor
Evaluate the side effects of JAK-1/2 inhibitor therapy in patients with Aicardi-Goutières Syndrome or AGS-related interferonopathies.
Measured: After 6, 12, 18, and 24 months of treatment, if the data is available.
Secondary outcomes (6)
Consensus on indication of JAK-1/2 Inhibitor Therapy for Aicardi-Goutières Syndrome and Related Interferonopathies on Clinical criteria (AGS scale)
Develop a possible consensus within the AGS Italia network on AGS scale criteria that define the indication for starting JAK-1/2 inhibitor therapy in Aicardi-Goutières Syndrome or AGS-related interferonopathies. The Aicardi-Goutières Syndrome (AGS) Severity Scale is a clinical tool used to assess the severity of neurological impairment in individuals with AGS. The scale ranges from 0 to 11, with higher scores indicating better neurological function.
Measured: Until study completion, an average of 2 year.
Consensus on indication of JAK-1/2 Inhibitor Therapy for Aicardi-Goutières Syndrome and Related Interferonopathies on genetic criteria (type of Genetic mutation)
Develop a possible consensus within the AGS Italia network on Genetic mutation that define the indication for starting JAK-1/2 inhibitor therapy in Aicardi-Goutières Syndrome or AGS-related interferonopathies. At now nine causative genes for Aicardi-Goutières Syndrome (AGS) are known: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, IFIH1, LSM11, and RNU7-1, all involved in nucleic acid metabolism and the interferon pathway.
Measured: Until study completion, an average of 2 year.
Consensus on indication of JAK-1/2 Inhibitor Therapy for Aicardi-Goutières Syndrome and Related Interferonopathies on laboratory parameter (IFN signature)
Develop a possible consensus within the AGS Italia network on laboratory parameter (IFN signature) that define the indication for starting JAK-1/2 inhibitor therapy in Aicardi-Goutières Syndrome or AGS-related interferonopathies.
The IFN Score is typically expressed as a fold change relative to healthy controls or as a normalized relative value, measuring the expression of interferon-stimulated genes (ISGs). In patients with pathological activation of the interferon pathway, the IFN Score ranges from 0 to >10-15, indicating significant ISG upregulation. While the pathological cut-off varies across studies, an IFN Score >2-3 is often considered indicative of abnormal interferon pathway activation.
Measured: Until study completion, an average of 2 year.
Consensus on Monitoring laboratory parameter (IFN signature) for JAK-1/2 Inhibitor Therapy in Aicardi-Goutières Syndrome and Related Interferonopathies
Develop a possible consensus within the AGS Italia network on laboratory parameter (IFN signature) to be monitored during JAK-1/2 inhibitor therapy to assess the potential continuation or discontinuation due to lack of efficacy. The IFN Score is typically expressed as a fold change relative to healthy controls or as a normalized relative value, measuring the expression of interferon-stimulated genes (ISGs). In patients with pathological activation of the interferon pathway, the IFN Score ranges from 0 to >10-15, indicating significant ISG upregulation. While the pathological cut-off varies across studies, an IFN Score >2-3 is often considered indicative of abnormal interferon pathway activation.
Measured: Until study completion, an average of 2 year.
Consensus on Monitoring Clinical criteria (AGS scale) for JAK-1/2 Inhibitor Therapy in Aicardi-Goutières Syndrome and Related Interferonopathies
Develop a possible consensus within the AGS Italia network on Clinical criteria (AGS scale) to be monitored during JAK-1/2 inhibitor therapy to assess the potential continuation or discontinuation due to lack of efficacy. The Aicardi-Goutières Syndrome (AGS) Severity Scale is a clinical tool used to assess the severity of neurological impairment in individuals with AGS. The scale ranges from 0 to 11, with higher scores indicating better neurological function.
Measured: Until study completion, an average of 2 year.
Consensus on instrumental parameters (brain MRI) for JAK-1/2 Inhibitor Therapy in Aicardi-Goutières Syndrome and Related Interferonopathies
Develop a possible consensus within the AGS Italia network on brain MRI to be monitored during JAK-1/2 inhibitor therapy to assess the potential continuation or discontinuation due to lack of efficacy. Evaluate based on the progression of brain MRI to determine whether it improves, remains stable, or worsens.
Measured: Until study completion, an average of 2 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2025
- Study start7 Apr 2024
- Primary completion18 Dec 2024
- Study completion18 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aicardi-Goutières Syndrome (AGS)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
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS Fondazione Stella Maris
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Roberta Battini, IRCCS Fondazione Stella Maris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06898372
- Sponsor's protocol ID
- AGS-AntiJak1
- Status last verified
- Mar 2025
- First submitted
- 5 Mar 2025
- Last updated
- 27 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: A common format (Case Report Form, CRF) for all the centers involved in the study will be used to record data for each enrolled patient. In addition, all data related to the study have been and will be shared through a mailing list.
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Retrospective Observational Study to Evaluate the Efficacy of Anti-Jak1 Inhibitors as Treatment for Patients With Aicardi-Goutières Syndrome
- ClinicalTrials.gov ID
- NCT06898372
- Acronym / sponsor ID
- AGS-AntiJak1
- Conditions
- Aicardi-Goutières Syndrome (AGS)
- Keywords
- Anti-Jak1/2, Ruxolitinib, Baricitinib, AGS-related interferonopathies
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- IRCCS Fondazione Stella MarisUniversity, hospital or other
- Study start
- 7 Apr 2024 (actual)
- Primary completion
- 18 Dec 2024 (actual)
- Study completion
- 18 Dec 2024 (actual)
- First posted
- 27 Mar 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.
Aicardi-Goutières Syndrome (AGS) is a hereditary multisystem autoinflammatory disorder that predominantly affects the central nervous system. It is characterized by severe neurological disability and chronic inflammation caused by the persistent overproduction of type I interferon. To date, nine causative genes of AGS have been identified, each of which can lead to classic AGS presentations, atypical forms, or other manifestations that do not meet the formal diagnostic criteria for AGS and are referred to as "AGS-related interferonopathies." Janus Kinase 1 (JAK1) inhibitors, including Baricitinib and Ruxolitinib, offer a promising therapeutic strategy for Aicardi-Goutières Syndrome (AGS) by directly targeting the central pathogenic pathway of the disease.
Patients treated with JAK1 inhibitors for AGS have shown significant improvement in systemic symptoms, though the effect on neurological symptoms and brain imaging remains unclear.
The aim of this project is to retrospectively analyze the efficacy, particularly on neurological symptoms and brain imaging, and the safety of JAK1 inhibitor treatment in AGS patients treated at Italian tertiary centers. Data will be collected before starting the therapy and during follow-up at 6, 12, 18, and 24 months, where available.
Preliminary data collection was carried out through a survey conducted by the AGS Italy group to assess the number of patients treated with JAK1 inhibitors.
Clinical, brain imaging, genetic, and laboratory data routinely recorded in nine different Italian centers as part of the standard clinical care of these patients will be retrospectively collected and analyzed.
In the second phase of the study, brain MRI data from AGS patients treated with JAK1 inhibitors will be compared to untreated AGS patients matched for age and genotype, in order to evaluate the potential therapeutic efficacy of JAK1 inhibitors on brain imaging compared to the natural clinical progression of the disease.
Through the analysis of the Italian experience, this study could lay the groundwork for drafting a potential consensus on the use of JAK1 inhibitors for the treatment of AGS patients.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with AAGS or AGS-related interferonopathies treated with Anti-Jak1/2 | – | Drug: JAK InhibitorStudy group: 1. Patients aged 0 to 25 years 2. Genetic diagnosis of Aicardi-Goutières Syndrome or AGS-related interferonopathies 3. Treatment with Janus Kinase 1/2 (JAK1/2) inhibitors, including Baricitinib and Ruxolitinib |
| Patients with AGS or AGS-related interferonopathies not treated with Anti-Jak1/2 | – | –Control group: 1. Patients aged 0 to 25 years matched with the study cases 2. Genetic diagnosis of Aicardi-Goutières Syndrome or AGS-related interferonopathies with genotype matched to the study cases 3. Not treated with Janus Kinase 1/2 (JAK1/2) inhibitors, such as Baricitinib and Ruxolitinib |
Who may qualify
- Ages
- 0 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- A total of approximately 24 patients with Aicardi-Goutières Syndrome or AGS-related interferonopathies are expected to be enrolled, including 12 patients treated with different Janus Kinase 1/2 (JAK1/2) inhibitors, such as Baricitinib and Ruxolitinib, and 12 untreated patients, from the 9 Italian clinical centers involved in the study.
Key inclusion criteria (2 listed)
- Patients aged 0 to 25 years
- Patients who have been genetically diagnosed with Aicardi-Goutières Syndrome (AGS) or AGS-related interferonopathies For case cohort-Patients treated with Janus Kinase 1/2 (JAK1/2) inhibitors, such as Baricitinib or Ruxolitinib
Key exclusion criteria (2 listed)
- Patients over the age of 25 years
- Patients who have not been genetically diagnosed with Aicardi-Goutières Syndrome (AGS) or AGS-related interferonopathies.
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 |
|---|---|---|
| JAK InhibitorThe retrospective analysis will examine the effects of Janus Kinase 1/2 (JAK1/2) inhibitors, such as Baricitinib and Ruxolitinib, on neurological symptoms and brain MRI. | Drug | Patients with AAGS or AGS-related interferonopathies treated with Anti-Jak1/2 |
Primary outcome
Efficacy of JAK-1/2 inhibitor therapy on Clinical criteria (AGS scale)
Time frame: After 6, 12, 18, and 24 months of treatment, if the data is available.
Evaluate the efficacy of JAK-1/2 inhibitor therapy through clinical criteria (AGS scale) in all patients with Aicardi-Goutières Syndrome or AGS-related interferonopathies, highlighting potential differences in efficacy between the different genotypes. The Aicardi-Goutières Syndrome (AGS) Severity Scale is a clinical tool used to assess the severity of neurological impairment in individuals with AGS. The scale ranges from 0 to 11, with higher scores indicating better neurological function.
Efficacy of JAK-1/2 inhibitor therapy on laboratory parameter (IFN signature)
Time frame: After 6, 12, 18, and 24 months of treatment, if the data is available.
Evaluate the efficacy of JAK-1/2 inhibitor therapy through IFN signature (IFN score) on blood in all patients with Aicardi-Goutières Syndrome or AGS-related interferonopathies, highlighting potential differences in efficacy between the different genotypes. The IFN Score is typically expressed as a fold change relative to healthy controls or as a normalized relative value, measuring the expression of interferon-stimulated genes (ISGs). In patients with pathological activation of the interferon pathway, the IFN Score ranges from 0 to >10-15, indicating significant ISG upregulation. While the pathological cut-off varies across studies, an IFN Score >2-3 is often considered indicative of abnormal interferon pathway activation.
Efficacy of JAK-1/2 inhibitor therapy on instrumental parameters (brain MRI)
Time frame: After 6, 12, 18, and 24 months of treatment, if the data is available.
Evaluate the efficacy of JAK-1/2 inhibitor therapy through brain MRI (Improved/Unchanged/Worsening) in all patients with Aicardi-Goutières Syndrome or AGS-related interferonopathies, highlighting potential differences in efficacy between the different genotypes.
Evaluate the side effects of JAK-1/2 inhibitor
Time frame: After 6, 12, 18, and 24 months of treatment, if the data is available.
Evaluate the side effects of JAK-1/2 inhibitor therapy in patients with Aicardi-Goutières Syndrome or AGS-related interferonopathies.
6 secondary outcomes
Consensus on indication of JAK-1/2 Inhibitor Therapy for Aicardi-Goutières Syndrome and Related Interferonopathies on Clinical criteria (AGS scale)
Time frame: Until study completion, an average of 2 year.
Consensus on indication of JAK-1/2 Inhibitor Therapy for Aicardi-Goutières Syndrome and Related Interferonopathies on genetic criteria (type of Genetic mutation)
Time frame: Until study completion, an average of 2 year.
Consensus on indication of JAK-1/2 Inhibitor Therapy for Aicardi-Goutières Syndrome and Related Interferonopathies on laboratory parameter (IFN signature)
Time frame: Until study completion, an average of 2 year.
Consensus on Monitoring laboratory parameter (IFN signature) for JAK-1/2 Inhibitor Therapy in Aicardi-Goutières Syndrome and Related Interferonopathies
Time frame: Until study completion, an average of 2 year.
Consensus on Monitoring Clinical criteria (AGS scale) for JAK-1/2 Inhibitor Therapy in Aicardi-Goutières Syndrome and Related Interferonopathies
Time frame: Until study completion, an average of 2 year.
Consensus on instrumental parameters (brain MRI) for JAK-1/2 Inhibitor Therapy in Aicardi-Goutières Syndrome and Related Interferonopathies
Time frame: Until study completion, an average of 2 year.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2025.
- Individual participant dataSharing planned: Yes. A common format (Case Report Form, CRF) for all the centers involved in the study will be used to record data for each enrolled patient. In addition, all data related to the study have been and will be shared through a mailing list.
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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Aicardi-Goutières Syndrome (AGS), run by IRCCS Fondazione Stella Maris at 1 site in Italy.
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 2 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: finished, as of the sponsor's last update on 27 Mar 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 Italy. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of JAK-1/2 inhibitor therapy on Clinical criteria (AGS scale) (time frame: After 6, 12, 18, and 24 months of treatment, if the data is available.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Mar 2025.