Tofatib Treatment for IgG4-related Disease

Clinical Study on the Efficacy and Safety of Tofatib and Cyclophosphamide in the Treatment of Active IgG4 Related Diseases

Compared with cyclophosphamide, the efficacy and safety of tofacitinib in the treatment of active IgG4-related diseases were evaluated.

Study Overview

• Status: Recruiting
• Conditions: IgG4-related Disease
• Intervention / Treatment: Drug: tofacitinib

Detailed Description

This study is a prospective, single center, non randomized, controlled, open label clinical observation study to evaluate the efficacy and safety of tropitib versus cyclophosphamide in inducing remission in IgG4-RD patients.

2) Investigators observe the diagnosis and treatment of IgG4-RD patients, and only provide patients with clinically appropriate diagnosis and treatment proposals.

It does not interfere with the choice of treatment plan for patients with the study drug of tropib or cyclophosphamide. If the patient chooses the hormone combined with tofatib or the hormone combined with cyclophosphamide as the main treatment drug, and at the same time meets the inclusion and exclusion criteria of this study, the patient can be included in this clinical observation study and become a subject. The experimental group was treated with glucocorticoid combined with tofatib, and the control group was treated with glucocorticoid combined with cyclophosphamide. It is planned that 20 people in each group will be treated for 6 months. After the study, the number of subjects in each group shall be at least 20 according to the actual situation. In the final statistical analysis, ensure that the sample size of the two groups participating in the statistical analysis is controlled at about 1:1.

3) The primary end point of this study was to compare the remission rate of the two groups after treatment; The secondary end point was to compare the response rate, recurrence rate and adverse event rate of the two groups after treatment.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Gao Jie, doctor; Phone Number: 13585561861; Email: gaojif@qq.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Recruiting
      • Shanghai Changhai Hospital
      • Contact: Gao Jie, doctor; Phone Number: 13585561861; Email: gaojif@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

IgG4-RD

Description

Inclusion Criteria:

• It meets the 2019 ACR/EULAR classification diagnostic criteria for IgG4 related diseases, and is an active IgG4-RD, defined as an IgG4-RD RI score ≥ 3 points when screening

Exclusion Criteria:

• 1. IgG4 related diseases endangering organ function or life;

  2. Only Mikulicz disease, no other internal organs involved;

  3. People with history of thrombotic disease or high risk of thrombosis;

  4. Have a history of malignant tumor;

  5. Active infection;

  6. Pregnant or lactating women;

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Glucocorticosteroids combined with Cyclophosphamide Group; Glucocorticoid: 0.5-1.0 mg/kg/d prednisone (or other glucocorticoids of equivalent dose) for 1 month (visit V2-V3), then reduced by 5 mg every 2 weeks, and maintained at 5-10 mg/day to visit V8. Cyclophosphamide: intravenous infusion, once a month, 0.5-1g/m2 each time, 6 times in total, until the end of visit V7.	Drug: tofacitinib; All subjects were treated immediately after non randomized enrollment. The treatment scheme of the experimental group: glucocorticoid+tropitib; the treatment scheme of the control group: glucocorticoid+cyclophosphamide.; Other Names: cyclophosphamide
Glucocorticoids combined with tofacitinib Group; Glucocorticoid: 0.5-1.0 mg/kg/d prednisone (or other glucocorticoids of equivalent dose) for 1 month (visit V2-V3), then reduced by 5 mg every 2 weeks, and maintained at 5-10 mg/day to visit V8. Tofacitinib: oral, twice a day, 5mg each time, lasting for 6 months, until the end of visit V8.	Drug: tofacitinib; All subjects were treated immediately after non randomized enrollment. The treatment scheme of the experimental group: glucocorticoid+tropitib; the treatment scheme of the control group: glucocorticoid+cyclophosphamide.; Other Names: cyclophosphamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease remission rate at 1 month, 3 months and 6 months of treatment (%)	Definition of disease remission: including ① complete remission (CR) (main efficacy index), partial remission (PR), continuous complete remission (CCR) and no change (NC).	1 month, 3 months and 6 months of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate at 1 month, 3 months and 6 months after treatment (%)	Defined as IgG4-RD RI score decrease ≥ 1 point	1 month, 3 months and 6 months after treatment
Disease recurrence rate at 3 and 6 months after treatment (%)	There are two types of disease recurrence, clinical recurrence and serological recurrence. Clinical recurrence was defined as recurrence of clinical symptoms or deterioration of imaging findings, with or without elevated serum IgG4 levels; Serological relapse was defined as an increase in serum IgG4 level and an increase in IgG4-RD RI score of ≥ 1 point after treatment, without recurrence of clinical symptoms or deterioration of imaging manifestations. The isolated increase of serum IgG4 concentration only constitutes serological recurrence. The date of recurrence is the date of onset of symptoms, or the date of new or deteriorated physical examination, laboratory examination or radiological examination results.	3 and 6 months after treatment
Changes in physician's overall assessment (PGA) from baseline at 1 month, 3 months and 6 months of treatment	First, the doctor evaluated the overall situation of IgG4 - RD subjects and marked them at the corresponding position of the straight line in the form of a vertical vertical line "l". The straight line is a 100mm scale, where the 0 end of the straight line represents very good, and the 100mm end represents very poor.	1 month, 3 months and 6 months of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the number of organs involved and IgG4-RD RI scores from the baseline after 6 months of treatment	The IgG4-RD RI value is obtained by superimposing the individual organ/site score of the patient. The score range of each organ/part is 0-3 points, which is defined as follows: 0 point means that the organ/part is not involved or completely relieved; 1: The lesions improved but still existed; 2 points: (after drug withdrawal) there was a new disease or recurrence of the previously involved site, or the disease did not improve after treatment; 3 Divided into (despite treatment) deterioration of lesions or new lesions. *When the disease of an important affected organ is urgent and requires active treatment, the score of the organ shall be doubled.	6 months of treatment
Changes of IgG4 level and related immunological indicators from baseline after 6 months of treatment	Relevant immune indicators include erythrocyte sedimentation rate, CRP, immunoglobulin, complement, IgG4, ANA spectrum, RF, ANCA, lymphocyte subsets, and cellular factor	6 months of treatment

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Investigators: Study Chair: Gao Jie, doctor, Changhai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2022
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: November 10, 2022
• First Submitted That Met QC Criteria: November 15, 2022
• First Posted (Actual): November 23, 2022

Study Record Updates

• Last Update Posted (Actual): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 15, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Immunoglobulin G4-Related Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Protein Kinase Inhibitors; Cyclophosphamide; Tofacitinib
• Other Study ID Numbers: CHEC2022-175

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No