Efficacy and Safety of Tofacitinib in Refractory Blau Syndrome

Efficacy and Safety of Tofacitinib in Patients with Refractory Blau Syndrome: a Prospective Cohort Study

This is a prospective cohort study to observe the efficacy and safety of Tofacitinib in children with Blau syndrome (BS). The investigators would analyze the rate of remission or low disease activity after treatment as well as changes in inflammatory markers, patients' and physician's global assessment of disease activity to determine the efficacy and safety of Tofacitinib.

Study Overview

• Status: Enrolling by invitation
• Conditions: Blau Syndrome
• Intervention / Treatment: Drug: Janus Kinase Inhibitor

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who have pathogenic mutation(s) in NOD2 gene;
• Patients who have clinical manifestations such as granulomatous dermatitis, arthritis, uveitis, vasculitis, interstitial lung disease and so on;
• Clinical remission was not achieved after ≥12 weeks of treatment with at least one immunosuppressant or biologics.

Exclusion Criteria:

Patients will not be included if meets any of the following criteria:

• Being treated with IL-1 inhibitor, or other biological agents;
• Pregnant and lactating women;
• Serious organ function failure, expected life time less than 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Janus kinase inhibitors; Tofacitinib is used according to weight: 5~<7kg，2mg；7~<10kg，2.5mg；10~<15kg，3mg；15~<25kg，3.5mg；25~<40kg，4mg；≥40kg，5mg. All is twice a day.	Drug: Janus Kinase Inhibitor; Tofacitinib is used according to weight: 5~<7kg，2mg；7~<10kg，2.5mg；10~<15kg，3mg；15~<25kg，3.5mg；25~<40kg，4mg；≥40kg，5mg. All is twice a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
rate of remission or low disease activity	From enrollment to the end of treatment at 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RCB(Response in Chinese children with Blau syndrome) 30, 50, 70 response rates		From enrollment to the end of treatment at 3, 6, 9, 12 months
Changes in inflammatory markers (including erythrocyte sedimentation rate, C reactive protein), cytokines (including IL-1β, IL-6, IL-17, IL-18, TNFα, IFN γ) and expression of type I interferon-stimulated genes over baseline	Changes are standardized as the ratio of the numerical difference before and after treatment to the baseline value	From enrollment to the end of treatment at 1,3, 6, 9, 12 months
Proportion of recurrent uveitis		From enrollment to the end of treatment at 12 months
Incidence of new organ involvement		From enrollment to the end of treatment at 1,3, 6, 9, 12 months
Number of participants with adverse effect		From enrollment to the end of treatment at 12 months

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: October 22, 2024
• First Submitted That Met QC Criteria: October 24, 2024
• First Posted (Actual): October 28, 2024

Study Record Updates

• Last Update Posted (Actual): October 28, 2024
• Last Update Submitted That Met QC Criteria: October 24, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Janus kinase inhibitors; Blau syndrome
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Pathologic Processes; Joint Diseases; Disease; Eye Diseases; Uveal Diseases; Arthritis; Syndrome; Uveitis; Synovitis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Janus Kinase Inhibitors
• Other Study ID Numbers: K6581

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No