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Effect of Tofacitinib in Treating ANCA-associated Vasculitis

Primary Purpose

ANCA Associated Vasculitis, Drug Use, JAK-STAT Pathway Deregulation

Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Tofacitinib
Sponsored by
Shanghai Zhongshan Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ANCA Associated Vasculitis focused on measuring ANCA associated vasculitis, tofacitinib, safety, efficacy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Department of Rheumatology in Zhongshan hospital, Fudan University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tofactitinib

Arm Description

Tofacitinib 5mg twice a day

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Changes in erythrocyte sedimentation rate (ESR)
The change of ESR in different follow-up point compared with the baseline.
Changes in CRP
The change of CRP in different follow-up point compared with the baseline.
Changes in glucocorticoids steroids (GCs) dosage
The change of the prednisone or its equivalent drug in different follow-up point compared with the baseline.

Full Information

First Posted
July 5, 2021
Last Updated
July 20, 2021
Sponsor
Shanghai Zhongshan Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04973033
Brief Title
Effect of Tofacitinib in Treating ANCA-associated Vasculitis
Official Title
Tofacitinib for the Treatment of Anti-Neutrophil Cytoplasm Antibody-associated Vasculitis: a Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
December 1, 2019 (Actual)
Primary Completion Date
January 31, 2021 (Actual)
Study Completion Date
January 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Zhongshan Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ANCA Associated Vasculitis, Drug Use, JAK-STAT Pathway Deregulation
Keywords
ANCA associated vasculitis, tofacitinib, safety, efficacy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tofactitinib
Arm Type
Experimental
Arm Description
Tofacitinib 5mg twice a day
Intervention Type
Drug
Intervention Name(s)
Tofacitinib
Other Intervention Name(s)
Tofacitinib 5mg.bid.po.
Intervention Description
patients enrolled were prescribed tofacitinib 5mg twice a day orally.
Primary Outcome Measure Information:
Title
The response rate (CR, PR and TR)
Description
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.
Time Frame
From the enrollment to the end of follow-up [0 to 13 months.]
Secondary Outcome Measure Information:
Title
The rate of adverse event
Description
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.
Time Frame
From the enrollment to the end of follow-up [0 to 13 months].
Title
Changes in erythrocyte sedimentation rate (ESR)
Description
The change of ESR in different follow-up point compared with the baseline.
Time Frame
From the enrollment to the end of follow-up [0 to 13 months].
Title
Changes in CRP
Description
The change of CRP in different follow-up point compared with the baseline.
Time Frame
From the enrollment to the end of follow-up [0 to 13 months].
Title
Changes in glucocorticoids steroids (GCs) dosage
Description
The change of the prednisone or its equivalent drug in different follow-up point compared with the baseline.
Time Frame
From the enrollment to the end of follow-up [0 to 13 months].

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lindi Jiang, PhD
Organizational Affiliation
Fudan University
Official's Role
Study Chair
Facility Information:
Facility Name
Department of Rheumatology in Zhongshan hospital, Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China

12. IPD Sharing Statement

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Effect of Tofacitinib in Treating ANCA-associated Vasculitis

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