Effect of Tofacitinib in Treating ANCA-associated Vasculitis

Drug Use Clinical Trial

Official title:

Tofacitinib for the Treatment of Anti-Neutrophil Cytoplasm Antibody-associated Vasculitis: a Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04973033
• Other study ID #: TofAV
• Status: Completed
• Phase: N/A
• Start date: December 1, 2019
• Est. completion date: January 31, 2021

Study information

• Verified date: July 2021
• Source: Shanghai Zhongshan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to evaluate the efficacy and safety of tofacitinib 5 mg twice daily in AAV patients.

Description:

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) represents a group of small vessel vasculitides characterized by granulomatous and neutrophilic tissue inflammation, often associated with the production of antibodies that target neutrophil antigens. The predominantly used treatment for induction of remission in AAV consisted of cyclophosphamide (CYC) plus corticosteroids (GCs) which leads to remission in about 90% of patients. However, relapses are frequent and remain a challenge. The optimal drug for maintenance treatment is not determined. Tofacitinib is a Jak inhibitor which has been proved to be effective in multiple inflammatory diseases such as rheumatoid arthritis. Considering that T cells and associated cytokine production play an important role in the pathogenesis of AAV via activation of the JAK/ STAT pathway, we hypothesized that tofacitinib-mediated inhibition of JAK signaling may represent an effective therapy for active AAV. In this prospective, open label, single arm study, tofacitinib 5mg twice a day will be added to the background treatment of GCs and immunosuppressants in AAV, the safety and efficacy of tofacitinib will be assessed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 31, 2021
• Est. primary completion date: January 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients with active AAV met the criteria of 1990 ACR and 2012 Chapel Hill criteria

• Age 18 to 75 years

• Written informed consent obtained before taking part in the study

Exclusion Criteria:

• Severe AAV defined as potentially organ- or life-threatening disease (i.e. alveolar haemorrhage, heart failure caused by myocarditis or pericarditis, progressive neurological symptoms, deaf, blindness, et al.)

• Serum creatinine>120umol/L or proteinuria>1.0g/d

• Receipt of a JAKi therapy previously

• Co-existence of another systemic autoimmune disease

• Secondary vasculitis (following neoplastic disease, an infection or antithyroid drugs)

• Malignancy or history of malignancy

• Infection by HIV, HCV, HBV or tuberculosis-

• Severe uncontrolled cardiovascular, pulmonary, liver, gastrointestinal, endocrine, hematological, neurological, or psychiatric diseases that are not related to systemic vasculitis

• Allergic to JAKi

• Blood dyscrasias including confirmed: Hemoglobin <9 g/dL or Hematocrit <30%; White blood cell count <3.0 x 109/L; Absolute neutrophil count <1.5 x 109/L; Platelet count <100 x 109/L; Alanine transaminase or aspartate aminotransferase or total bilirubin>1.5 upper normal limit; Estimated glomerular filtration rate<60ml/min/1.73m2

• Incapacity or refusal to understand or sign the informed consent form.

• Pregnancy, breastfeeding.

Related Conditions & MeSH terms

• ANCA Associated Vasculitis
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
• Drug Use
• JAK-STAT Pathway Deregulation
• Vasculitis

Intervention

Drug:
• Tofacitinib
patients enrolled were prescribed tofacitinib 5mg twice a day orally.

Locations

Country	Name	City	State
China	Department of Rheumatology in Zhongshan hospital, Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The response rate (CR, PR and TR)	The percent of patients who achieved disease response. The disease response includes:(1) complete remission (CR), defined as the absence of disease activity (BVAS = 0); (2) partial remission (PR) defined as at least 50% reduction of BVAS and no new manifestations; (3) treatment resistance (TR) was defined as less than a 50% reduction or increased disease activity after 4 ~ 6 weeks of treatment.	From the enrollment to the end of follow-up [0 to 13 months.]
Secondary	The rate of adverse event	The percent of different kinds of adverse events occurred during follow-up. The adverse event was evaluated according to the CTC-AE 4.0 standard.	From the enrollment to the end of follow-up [0 to 13 months].
Secondary	Changes in erythrocyte sedimentation rate (ESR)	The change of ESR in different follow-up point compared with the baseline.	From the enrollment to the end of follow-up [0 to 13 months].
Secondary	Changes in CRP	The change of CRP in different follow-up point compared with the baseline.	From the enrollment to the end of follow-up [0 to 13 months].
Secondary	Changes in glucocorticoids steroids (GCs) dosage	The change of the prednisone or its equivalent drug in different follow-up point compared with the baseline.	From the enrollment to the end of follow-up [0 to 13 months].