Efficacy and Safety of Lenalidomide in Patients With IgG4-Related Disease

NCT07719543 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 301-Rheuma-0511
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 3

Brief Summary

Immunoglobulin G4-related disease (IgG4-RD) is a chronic immune-mediated disorder characterized by inflammation, fibrosis, and involvement of multiple organs. Although glucocorticoids can effectively induce remission, many patients experience disease relapse after glucocorticoid tapering or discontinuation, and long-term glucocorticoid exposure may cause significant adverse effects. Therefore, new maintenance treatment strategies are needed to reduce relapse risk and minimize glucocorticoid-related toxicity. This study is designed to evaluate the efficacy and safety of lenalidomide as a maintenance therapy in patients with stable IgG4-RD. This is a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial. Eligible participants will be adults with IgG4-RD who meet the 2019 ACR/EULAR IgG4-RD classification criteria and are in a stable disease state. Participants will be randomly assigned in a 1:1 ratio to receive either lenalidomide or matching placebo for 52 weeks. All participants will receive standardized glucocorticoid tapering according to the study protocol. The primary objective of this study is to determine whether lenalidomide can reduce the risk of IgG4-RD relapse compared with placebo. The primary outcome is the proportion of participants experiencing disease relapse within 52 weeks after randomization. Secondary objectives include evaluation of time to relapse, maintenance of remission, changes in disease activity, quality of life, and safety outcomes. Exploratory assessments will investigate changes in immunological biomarkers, peripheral blood immune profiles, transcriptomic characteristics, and gut microbiota. This study aims to provide clinical evidence for a new maintenance treatment approach for patients with IgG4-RD and potentially reduce disease recurrence and glucocorticoid exposure.

Conditions

Immunoglobulin G4-Related Disease

Keywords

IgG4-related disease; Lenalidomide; Maintenance therapy

Outcome Measures

Primary Outcomes (1)

• Cumulative relapse rate of IgG4-related disease at Week 52

  The proportion of participants experiencing at least one protocol-defined IgG4-related disease relapse from randomization to Week 52.

  From randomization to Week 52

Secondary Outcomes (2)

• Incidence of adverse events and serious adverse events

  From first dose of study intervention to Week 52

• Time to first IgG4-related disease relapse

  From randomization to Week 52

Other Outcomes (1)

• Changes in immunological biomarkers

  Baseline, Week 4, Week 8, Week 12, Week 26, Week 39, and Week 52

Study Arms (2)

Lenalidomide Arm

EXPERIMENTAL

Participants will receive lenalidomide 5 mg orally once daily for 52 weeks as maintenance therapy. All participants will undergo standardized glucocorticoid tapering according to the study protocol during the initial treatment period. Lenalidomide will be administered in addition to background glucocorticoid management.

Drug: Lenalidomide

Placebo Arm

PLACEBO COMPARATOR

Participants will receive matching placebo orally once daily for 52 weeks as maintenance therapy. All participants will undergo standardized glucocorticoid tapering according to the study protocol during the initial treatment period. The placebo will be identical in appearance, packaging, labeling, and administration procedures to lenalidomide.

Drug: Placebo

Interventions

Placebo DRUG

Matching placebo will be administered orally once daily for 52 weeks as maintenance therapy. The placebo will be identical to lenalidomide in appearance, packaging, labeling, and administration procedures. All participants will undergo standardized glucocorticoid tapering according to the study protocol during the initial treatment period.

Placebo Arm

Lenalidomide DRUG

Lenalidomide will be administered orally at a dose of 5 mg once daily for 52 weeks as maintenance therapy in participants with IgG4-related disease in sustained clinical remission. All participants will undergo standardized glucocorticoid tapering according to the study protocol during the initial treatment period.

Also known as: Len

Lenalidomide Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18 to 75 years at the time of screening.
• Diagnosis of IgG4-related disease according to the 2019 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria.
• Patients with IgG4-related disease who have achieved sustained clinical remission following glucocorticoid therapy.
• No documented IgG4-related disease relapse within the previous 12 months before screening.
• IgG4-related disease Responder Index (IgG4-RD RI) score of 0 at screening.
• Receiving stable low-dose glucocorticoid therapy with prednisone-equivalent dose ≤7.5 mg/day for at least 6 months before randomization.
• Ability to provide written informed consent and comply with study procedures.

You may not qualify if:

• Active IgG4-related disease requiring induction therapy or escalation of immunosuppressive treatment at screening.
• Previous treatment with lenalidomide or known hypersensitivity to lenalidomide or related compounds.
• Requirement for prohibited concomitant medications during the study period.
• Significant uncontrolled infection or active severe infection.
• Clinically significant hematologic abnormalities, including severe neutropenia or thrombocytopenia.
• Significant hepatic or renal dysfunction that may affect study participation or drug safety evaluation.
• History of thromboembolic events or conditions associated with unacceptable thrombotic risk according to investigator assessment.
• Pregnancy, breastfeeding, or unwillingness to use effective contraception when applicable.
• Malignancy or other severe medical conditions that may interfere with study participation or outcome assessment.
• Any condition that, in the investigator's opinion, may compromise participant safety or affect the reliability of study results.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead
• Beijing SL Pharmaceutical Co., Ltd.: collaborator

Study Sites (3)

The First Medical Center of Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

Location

Hainan Hospital of Chinese PLA General Hospital

Sanya, Hainan, 572013, China

Location

General Hospital of Central Theater Command

Wuhan, Hubei, 430070, China

Location

Related Publications (5)

• Chen Y, Ye C, Yang P, Zhang W, Dai L, Wei W, Wu R, Ding S, Chen L, Wu X, Zhao J, Liao C, Sun W, Umehara H, Cai S, Dong L. Thalidomide can effectively prevent relapse in IgG4-related disease outweighing its side effects: a multicentre, randomised, double-blinded, placebo-controlled study. Ann Rheum Dis. 2025 Jul;84(7):1246-1252. doi: 10.1016/j.ard.2025.01.033. Epub 2025 Feb 16.

  PMID: 39956699 RESULT

• Hegi ME, Liu L, Herman JG, Stupp R, Wick W, Weller M, Mehta MP, Gilbert MR. Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity. J Clin Oncol. 2008 Sep 1;26(25):4189-99. doi: 10.1200/JCO.2007.11.5964.

  PMID: 18757334 RESULT

• Wood JS, Donnell ET, Porter RJ. Comparison of safety effect estimates obtained from empirical Bayes before-after study, propensity scores-potential outcomes framework, and regression model with cross-sectional data. Accid Anal Prev. 2015 Feb;75:144-54. doi: 10.1016/j.aap.2014.11.019. Epub 2014 Dec 3.

  PMID: 25481539 RESULT

• Jellett AP, Jenks K, Lucas M, Scott RC. Standard dose valproic acid does not cause additional cognitive impact in a rodent model of intractable epilepsy. Epilepsy Res. 2015 Feb;110:88-94. doi: 10.1016/j.eplepsyres.2014.11.005. Epub 2014 Nov 21.

  PMID: 25616460 RESULT

• Hou Z, Wang RJ, Tang JF, Yuan H, Xiang GY, Li CF, Guo GC. Control-Enhanced Sequential Scheme for General Quantum Parameter Estimation at the Heisenberg Limit. Phys Rev Lett. 2019 Jul 26;123(4):040501. doi: 10.1103/PhysRevLett.123.040501.

  PMID: 31491234 RESULT

MeSH Terms

Conditions

Immunoglobulin G4-Related Disease

Interventions

Lenalidomide; vicilin protein, plant

Condition Hierarchy (Ancestors)

Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jian Zhu, MD, PhD

  The First Medical Center of Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yufei Guo, MD

CONTACT

+86 010-55499314; dt_guoyf0412@outlook.com

Yiwen Wang, MD

CONTACT

+86 010-55499314; yiwenvera@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind study. Participants, care providers, investigators, and outcome assessors will be blinded to treatment assignment. Lenalidomide and matching placebo will have identical appearance, packaging, labeling, and administration procedures. Treatment allocation will only be disclosed in emergency situations when necessary for participant management.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chief Physician

Model Details: Participants will be randomly assigned in a 1:1 ratio to receive either lenalidomide or matching placebo. The study consists of two parallel treatment arms with a 52-week randomized controlled treatment period.

Study Record Dates

• First Submitted: July 18, 2026
• First Posted: July 22, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: July 22, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 12 months after publication of the primary results and for 5 years thereafter.
• Access Criteria: Qualified researchers may request access to de-identified individual participant data and supporting documents. Requests will be reviewed by the study steering committee based on scientific merit, ethical considerations, and compliance with applicable regulations. Approved researchers will be required to complete a data use agreement before access is granted.

Locations

CN (3)