Administrative information
Title {1} | A multi-center, prospective, open-label, randomized study to explore efficacy and safety of baricitinib in active primary Sjogren’s syndrome patients |
---|---|
Trial registration {2a and 2b} | ClinicalTrials.gov, ID: NCT05016297 |
Protocol version {3} | Protocol Version 3.1, 30 January 2022 |
Funding {4} | This study is funded by Eli Lilly Trading Co., Ltd. |
Author details {5a} | Wei Bai1, Fan Yang1, Huji Xu2, Wei Wei3, Hongbin Li4, Liyun Zhang5, Yi Zhao6, Xiaofei Shi7, Yan Zhang8, Xiaofeng Zeng1, Xiaomei Leng1 1 Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH); Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing 100,730, China 2 Department of Rheumatology and Immunology, Changzheng Hospital, Naval Medical University, Shanghai, 200,003, China. 3 Department of Rheumatology, Tianjin Medical University General Hospital, Tianjin, China. 4 Department of Rheumatology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China. 5 Department of Rheumatology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital Shanxi Academy of Medical Sciences, Taiyuan, Shanxi, China. 6 Department of Rheumatology, Xuanwu Hospital, Capital Medical University, Beijing, China. 7 Department of Rheumatology, the First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan, China. 8 Department of Rheumatology, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), Xi’an, Shaanxi, China. |
Name and contact information for the trial sponsor {5b} | Dr. Xiaomei Leng Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH); Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing 100,730, China. Tel: + 86–10-69,155,646; Email: lpumch@126.com |
Role of sponsor {5c} | This is an investigator initiated clinical trial. Therefore, the funders played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. |
Introduction
Background and rationale {6a}
Objectives {7}
Trial design {8}
Methods: participants, interventions, and outcomes
Study setting {9}
Eligibility criteria {10}
Inclusion criteria
Exclusion criteria
Who will take informed consent? {26a}
Additional consent provisions for collection and use of participant data and biological specimens {26b}
Public and patient involvement
Interventions
Explanation for the choice of comparators {6b}
Intervention description {11a}
Criteria for discontinuing or modifying allocated interventions {11b}
Temporary interruption of investigational product
Laboratory measure | Action | Monitoring guidance |
---|---|---|
Absolute neutrophil count (ANC) | Treatment should be interrupted if ANC < 1 × 109 cells/L and may be restarted once ANC return above this value | Before treatment initiation (see exclusion criteria too) and thereafter according to routine patient management |
Absolute lymphocyte count (ALC) | Treatment should be interrupted if ALC < 0.5 × 109 cells/L and may be restarted once ALC return above this value | |
Hemoglobin (Hgb) | Treatment should be interrupted if Hgb < 8 g/dL and may be restarted once Hgb return above this value | |
Hepatic transaminases | Treatment should be temporarily interrupted if drug-induced liver injury is suspected |
Permanent discontinuation from investigational product
-
ALT or AST > 8 × upper limit of normal
-
ALT or AST > 5 × upper limit of normal for more than 2 weeks after temporary interruption of investigational product
-
ALT or AST > 3 × upper limit of normal and total bilirubin level > 2 × upper limit of normal
-
ALT or AST > 3 × upper limit of normal with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%)
-
WBC < 1 × 109 cells/L
-
ANC < 0.5 × 109 cells/L
-
ALC < 0.2 × 109 cells/L
-
Hgb < 6.5 g/dL
-
Pregnancy
-
Malignancy
-
Development of a VTE (DVT/PE) during the study
HBV DNA monitoring
Active TB monitoring
Strategies to improve adherence to interventions {11c}
Relevant concomitant care permitted or prohibited during the trial {11d}
Provisions for post-trial care {30}
Outcomes {12}
Primary outcome measure
Secondary outcome measure
Participant timeline {13}
− 4 weeks (screening) | 0 weeks (start medication) | 4 weeks | 8 weeks | 12 weeks (switch checkpoint) | 16 weeks | 20 weeks | 24 weeks (the end of study) | |
---|---|---|---|---|---|---|---|---|
Visit | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
informed consent | √ | |||||||
Medical history record | √ | |||||||
Vital signs | √ | √ | √ | √ | √ | √ | √ | √ |
Infection screening like hepatitis and TB | √ | √ | ||||||
complete blood cell count | √ | √ | √ | √ | √ | √ | √ | √ |
Renal and liver function test | √ | √ | √ | √ | √ | √ | √ | √ |
Urine routine test | √ | √ | √ | √ | √ | √ | √ | √ |
Acute phase reactants (ESR, CRP) | √ | √ | √ | √ | ||||
Autoantibodies (antinuclear antibody, anti-SSA, anti-SSB, et al.) | √ | √ | ||||||
Immunological parameters (Ig, complement, RF) | √ | √ | √ | |||||
Exocrine gland function | √ | √ | √ | |||||
Labial salivary gland biopsy | √ | √ | ||||||
PGA score | √ | √ | √ | √ | ||||
ESSDAI score | √ | √ | √ | √ | ||||
ESSPRI score | √ | √ | √ | √ | ||||
Adverse events | √ | √ | √ | √ | √ | √ | √ | √ |
Concomitant medication | √ | √ | √ | √ | √ | √ | √ | √ |
Sample size {14}
Recruitment {15}
Assignment of interventions: allocation
Sequence generation {16a}
Concealment mechanism {16b}
Implementation {16c}
Assignment of interventions: blinding
Who will be blinded {17a}
Procedure for unblinding if needed {17b}
Data collection and management
Plans for assessment and collection of outcomes {18a}
Plans to promote participant retention and complete follow-up {18b}
Data management {19}
Confidentiality {27}
Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}
Statistical methods
Statistical methods for primary and secondary outcomes {20a}
Methods for additional analyses {20b}
Interim analyses {21b}
Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}
Plans to give access to the full protocol, participant-level data, and statistical code {31c}
Oversight and monitoring
Composition of the coordinating center and trial steering committee {5d}
-
Principle investigator: takes supervision of the trial and medical responsibility of the patients.
-
Data manager: organizes data capture, safeguards quality and data.
-
Study physician: identifies potential recruits, takes informed consent, ensures follow-up and safety monitor according to protocol.