Clinical trial NCT06898372: Evaluate the Efficacy of Anti-Jak1 Inhibitors as Treatment for Patients With Aicardi-Goutières Syndrome
Official title: Multicenter Retrospective Observational Study to Evaluate the Efficacy of Anti-Jak1 Inhibitors as Treatment for Patients With Aicardi-Goutières Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Aicardi-Goutières Syndrome (AGS)
Keywords: Anti-Jak1/2
Ruxolitinib
Baricitinib
AGS-related interferonopathies
Lead sponsor: IRCCS Fondazione Stella Maris
Sponsor class: OTHER
First posted: 2025-03-27
Enrollment: 24
Sex: ALL
Minimum age (years): 0
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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. 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* Patients over the age of 25 years
* Patients who have not been genetically diagnosed with Aicardi-Goutières Syndrome (AGS) or AGS-related interferonopathies.

Primary outcomes:
measure: Efficacy of JAK-1/2 inhibitor therapy on Clinical criteria (AGS scale)
timeFrame: After 6, 12, 18, and 24 months of treatment, if the data is available.
measure: Efficacy of JAK-1/2 inhibitor therapy on laboratory parameter (IFN signature)
timeFrame: After 6, 12, 18, and 24 months of treatment, if the data is available.
measure: Efficacy of JAK-1/2 inhibitor therapy on instrumental parameters (brain MRI)
timeFrame: After 6, 12, 18, and 24 months of treatment, if the data is available.
measure: Evaluate the side effects of JAK-1/2 inhibitor
timeFrame: After 6, 12, 18, and 24 months of treatment, if the data is available.
Secondary outcomes:
measure: Consensus on indication of JAK-1/2 Inhibitor Therapy for Aicardi-Goutières Syndrome and Related Interferonopathies on Clinical criteria (AGS scale)
timeFrame: Until study completion, an average of 2 year.
measure: Consensus on indication of JAK-1/2 Inhibitor Therapy for Aicardi-Goutières Syndrome and Related Interferonopathies on genetic criteria (type of Genetic mutation)
timeFrame: Until study completion, an average of 2 year.
measure: Consensus on indication of JAK-1/2 Inhibitor Therapy for Aicardi-Goutières Syndrome and Related Interferonopathies on laboratory parameter (IFN signature)
timeFrame: Until study completion, an average of 2 year.
measure: Consensus on Monitoring laboratory parameter (IFN signature) for JAK-1/2 Inhibitor Therapy in Aicardi-Goutières Syndrome and Related Interferonopathies
timeFrame: Until study completion, an average of 2 year.
measure: Consensus on Monitoring Clinical criteria (AGS scale) for JAK-1/2 Inhibitor Therapy in Aicardi-Goutières Syndrome and Related Interferonopathies
timeFrame: Until study completion, an average of 2 year.
measure: Consensus on instrumental parameters (brain MRI) for JAK-1/2 Inhibitor Therapy in Aicardi-Goutières Syndrome and Related Interferonopathies
timeFrame: Until study completion, an average of 2 year.
Other outcomes:
Locations:
city: Pisa
country: Italy
facility: IRCCS Stella Maris Foundation
Study officials:
References: