Clinical trial NCT06662721: Baricitinib for Refractory Takayasu Arteritis
Official title: Baricitinib for Takayasu Arteritis Refractory to TNF-α Inhibitors: a Prospective Pilot Open-label Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Takayasu Arteritis
Keywords: Takayasu arteritis
Baricitinib
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2024-10-29
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Ten patients with Takayasu arteritis refractory to TNF-α inhibitors were treated with baricitinib.
Primary purpose: TREATMENT

Brief summary: Takayasu arteritis (TKA) is an autoimmune vasculitis characterized with involvement of aorta and its primary branches. For TKA refractory to TNF-α, Baricitinib, a reversible inhibitor of Janus kinases (JAK) family members JKA1 and JAK2, represents a potential treatment option. This study aims to assess the efficacy and safety of Baricitinib in TKA refractory to TNF-α inhibitors.

Detailed description: This is a multi-center, single-arm trial conducted to evaluate the safety and efficacy of baricitinib in Takayasu arteritis (TKA) refractory to TNF-α inhibitors. Patients in active TKA and unresponsive to at least 6 months of TNF-α inhibitors therapy were enrolled. Patients discontinued TNF-α inhibitors and received baricitinib at 4 mg/day for up to 48 weeks, which was added to the glucocorticoid and immunosuppressants. The clinical manifestations, inflammatory indicators, imaging and treatment of patients were recorded by investigators during the follow up.

Eligibility criteria: Inclusion Criteria:

* Male or female aged 18-70 years at time of screening.
* Diagnosis of Takayasu arteritis (according to the 2022 ACR/EULAR) for ≥3 months before screening.
* Active Takayasu arteritis at time of screening (NIH score≥2).
* Resistant to traditional therapies and anti-TNF-α therapy for at least 12 months.
* Given their written informed consent to participate in the trial and expected to be able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

* TKA-related active major organ involvement requiring immunosuppressive therapy, e.g., pulmonary (e.g., pulmonary artery aneurysm), vascular (e.g., thrombophlebitis, recurrent malignant aneurysms), gastrointestinal (e.g., gastrointestinal ulcers), and central nervous system (e.g., meningoencephalitis).
* High-dose glucocorticoid (\>1mg/kg/d) usage within 1 month.
* Severe comorbidities: including heart failure (≥ grade III NYHA), renal insufficiency (creatinine clearance ≤30 ml/min), hepatic insufficiency (serum ALT or AST \>3 times the ULN, or total bilirubin \>ULN for the central laboratory conducting the test). Other severe, progressive or uncontrolled hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease (including demyelinating diseases such as multiple sclerosis).
* Known allergies, hypersensitivity, or intolerance to Baricitinib or its excipients.
* Had a severe infection (including, but not limited to hepatitis, pneumonia, sepsis, or pyelonephritis); had been hospitalized for an infection; or had been treated with IV antibiotics for an infection, within 2 months prior to the first administration of study agent.
* Chest radiograph within 3 months prior to the first administration of study agent that showed an abnormality suggestive of a malignancy or current active infection, including tuberculosis.
* Infected with HIV (positive serology for HIV antibody) or hepatitis C (positive serology for Hep C antibody). If seropositive, consultation with a physician with expertise in the treatment of HIV or hepatitis C virus infection was recommended.
* Infected with hepatitis B virus. For patients who were not eligible for this study due to hepatitis B virus test results, consultation with a physician with expertise in the treatment of hepatitis B virus infection was recommended.
* Had any known malignancy or has a history of malignancy within the previous 5 years (with the exception of a nonmelanoma skin cancer that had been treated with no evidence of recurrence for ≥3 months before the first study agent administration or cervical neoplasia with surgical cure).
* Had uncontrolled psychiatric or emotional disorder, including a history of drug and alcohol abuse within the past 3 years that might prevent the successful completion of the study.
* Received, or was expected to receive, any live virus or bacterial vaccination within 3 months before the first administration of study agent, during the study, or within 4 months after the last administration of study agent. Had a BCG vaccination within 12 months of screening.
* Pregnancy, lactation or women of child-bearing potential (WCBP) unwilling to use medically approved contraception whilst receiving treatment and for 12 months after treatment has finished.
* Men whose partners are of child-bearing potential but who are unwilling to use appropriate medically approved contraception whilst receiving treatment and for 12 months after treatment has finished.

Primary outcomes:
measure: Patients achieving complete remission and partial remission
timeFrame: Week 24
Secondary outcomes:
measure: Changes of National Institutes of Health (NIH) score of patients
timeFrame: Week 24 and week 48
measure: Changes of Indian Takayasu Clinical Activity Score (ITAS2010) of patients
timeFrame: Week 24 and week 48
measure: Changes of C-reactive protein
timeFrame: Week 24 and week 48
measure: Changes of erythrocyte sedimentation rate
timeFrame: Week 24 and week 48
measure: Changes of dosage of glucocorticoids from baseline.
timeFrame: Week 24 and week 48
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Rheumatology and Immunology, Peking University People's Hospital
state: Beijing
Study officials:
References: