Baricitinib Plus Glucocorticoid for Eosinophilia in IgG4-RD

A Prospective, Randomized Controlled Study to Compare the Efficacy and Safety of Baricitinib Combined With Glucocorticoid and Glucocorticoid Monotherapy in Proliferative IgG4-RD Patients With Eosinophilia

Evaluation of efficacy and safety of Baricitinib combined with glucocorticoid in patients of IgG4-related disease with eosinophilia.

Study Overview

• Status: Recruiting
• Conditions: IgG4-related Disease With Eosinophilia
• Intervention / Treatment: Drug: Prednisolone; Drug: Baricitinib

Detailed Description

This is a multicenter, 52-week prospective, randomized controlled study to compare the efficacy and safety of Baricitinib combined with glucocorticoid and glucocorticoid monotherapy in proliferative IgG4-RD patients with eosinophilia.

• Study Type: Interventional
• Enrollment (Anticipated): 74
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Linyi Peng, MD; Phone Number: +8615810395901; Email: drpenglinyi@163.com

Study Locations

• China
  • Bejing
    • Beijing, Bejing, China, 100050
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Linyi Peng, MD; Phone Number: +8615810395901; Email: drpenglinyi@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. All patients must meet the following diagnostic criteria of IgG4RD (2020): 1) and radiological features: One or more organs show diffuse or localized swelling or a mass or nodule characteristic of IgG4-RD. In single organ involvement, lymph node swelling is omitted. 2) serological diagnosis: Serum IgG4 levels greater than 135 mg/dl. 3) diagnosis diagnosis: Positivity for two of the following three criteria: a. Dense lymphocyte and plasma cell infiltration with fibrosis. b. Ratio of IgG4-positive plasma cells /IgG-positive cells greater than 40% and the number of IgG4-positive plasma cells greater than 10 per high powered field. c. Typical tissue fibrosis, particularly storiform fibrosis, or obliterative phlebitis.

   Patients fulfill (1) + (2) + (3) are diagnosed as definite IgD4RD; (1) + (2): possible IgG4RD; (1) + (3): probable IgG4RD. exclusion of other diseases.

2. Active IgG4-RD (Responder Index ≥ 2 points for each involved organ)
3. The counts of peripheral blood eosinophil cells ≥0.75×109/L

Exclusion Criteria:

1. Patients who is not able to discontinue GC
2. Pregnancy or breastfeeding or planning to get pregnant within 2 years
3. Received glucocorticoids, immunosuppressants, biological agents or JAK inhibitors within 3 months
4. Allergic to Baricitinib
5. Concomitant other autoimmune diseases
6. Malignancy
7. Chronic HBV infection, latent tuberculosis, or active infection
8. Server liver or renal dysfunction, or heart failure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Prednisolone monotherapy; Oral prednisolone 0.6-0.8mg/kg daily for 4 weeks, then tapered and withdrawal in 4 months.	Drug: Prednisolone; Oral prednisolone 0.6-0.8mg/kg daily for 4 weeks, then tapered and withdrawal in 4 months.
Experimental: Prednisolone plus Baricitinib; Oral prednisolone 0.6-0.8mg/kg daily for 4 weeks, then tapered and withdrawal in 4 months. Oral Baricitinib 2mg daily for 12 months.	Drug: Prednisolone; Oral prednisolone 0.6-0.8mg/kg daily for 4 weeks, then tapered and withdrawal in 4 months.; Drug: Baricitinib; Oral Baricitinib 2mg daily for 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference of recurrent rate of IgG4-RD between the two groups	Clinical recurrence definition: any item of IgG4-RD Responder Index ≥2 (without treatment), or ≥ 3 (with treatment) or new organ involvement; with or without elevated serum IgG4 levels.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time of recurrence	Clinical recurrence definition: any item of IgG4-RD Responder Index ≥2 (without treatment), or ≥ 3 (with treatment) or new organ involvement; with or without elevated serum IgG4 levels.	0-52 weeks
The changes of blood Eosinophil cells	Percentages (%) and counts (109) of peripheral eosinophil cells	52 weeks
The changes of serum IgG levels	Level of serum IgG(g/L)	52 weeks
The changes of serum IgG4 levels	Level of serum IgG4(mg/dL)	52 weeks
The changes of serum hsCRP level	Level of serum high-sensitivity C-reactive protein level(mg/L)	52 weeks
The changes of ESR	Serum erythrocyte sedimentation rate(mm/h)	52 weeks
The percentages of adverse events	Adverse effect of drugs	52 weeks
The changes of PGA	Changes of patient global assessment from baseline, score (0-10, higher is worse)	52 weeks
The results of High-throughput analysis	The changes of results from baseline in High-throughput analysis, including GWAS, single cell sequencing of B cell receptor.	52 weeks
The changes of IgG4-related disease Responder Index	According to international multispecialty validation study of IgG4-related disease Responder Index (Version: 13, December, 2015), Responder Index ≥ 0, and higher scores mean a worse outcome.	52 weeks

Collaborators and Investigators

• Sponsor: Wen Zhang
• Collaborators: Beijing Friendship Hospital; Tongji Hospital
• Investigators: Principal Investigator: Wen Zhang, MD, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2023
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: March 12, 2023
• First Submitted That Met QC Criteria: March 12, 2023
• First Posted (Actual): March 23, 2023

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: eosinophilia; IgG4-related disease
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Leukocyte Disorders; Eosinophilia; Immunoglobulin G4-Related Disease; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisolone
• Other Study ID Numbers: Baricitinib for Eosinophilia

Drug and device information, study documents

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