Efficacy and Safety of Lenalidomide in Patients With IgG4-Related Disease (LENITY)
A Phase III Multicenter Randomized Double-Blind Placebo-Controlled Study Evaluating the Efficacy and Safety of Lenalidomide in Patients With IgG4-Related Disease
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Immunoglobulin G4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disorder characterized by lymphoplasmacytic infiltration, IgG4-positive plasma cell accumulation, storiform fibrosis, and involvement of multiple organs. Although glucocorticoids remain the standard first-line therapy for induction of remission, a substantial proportion of patients experience disease relapse during glucocorticoid tapering or after treatment discontinuation. In addition, prolonged glucocorticoid exposure is associated with clinically significant adverse effects, including metabolic complications, osteoporosis, cardiovascular risks, and increased susceptibility to infection. Therefore, effective and well-tolerated maintenance therapies are urgently needed to sustain remission and reduce relapse risk in patients with IgG4-RD.
Accumulating evidence indicates that persistent immune dysregulation contributes to disease recurrence in IgG4-RD even after clinical remission has been achieved. Aberrant B-cell activation, expansion of plasmablasts and plasma cells, dysregulated T-cell responses, and remodeling of the immune microenvironment are considered key components underlying disease persistence and relapse. Therapeutic strategies targeting pathogenic immune pathways, particularly those involving B-cell and plasma cell responses, have shown potential clinical benefits, supporting the concept that immune modulation during the remission phase may prevent disease recurrence.
Lenalidomide is an immunomodulatory agent with established clinical activity in plasma cell disorders and emerging applications in immune-mediated diseases. Through binding to cereblon (CRBN), lenalidomide promotes the degradation of specific immune regulatory transcription factors, including IKZF1 and IKZF3, thereby modulating B-cell activation, plasma cell differentiation, inflammatory cytokine production, and T-cell function. Given the central role of B-cell/plasma cell dysregulation in IgG4-RD pathogenesis, these immunomodulatory properties provide a scientific rationale for evaluating lenalidomide as a maintenance therapy in patients with IgG4-RD who have achieved sustained clinical remission.
This is a phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial designed to evaluate the efficacy and safety of lenalidomide as maintenance therapy for relapse prevention in patients with IgG4-RD in sustained clinical remission.
Approximately 146 participants will be enrolled. Eligible participants are adults with IgG4-RD who meet the 2019 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria and have achieved sustained disease control following glucocorticoid therapy. Participants must have no documented disease relapse within the preceding year, an IgG4-RD Responder Index (IgG4-RD RI) score of 0, and be receiving a stable low-dose glucocorticoid regimen before randomization.
Participants will be randomly assigned in a 1:1 ratio to receive either lenalidomide 5 mg orally once daily or matching placebo for 52 weeks. During the initial treatment period, all participants will undergo standardized glucocorticoid tapering according to the predefined protocol. The study adopts a double-blind design, with participants, investigators, outcome assessors, and relevant study personnel blinded to treatment allocation.
The primary objective of this study is to determine whether lenalidomide can reduce the risk of IgG4-RD relapse compared with placebo during the maintenance phase. The primary endpoint is the cumulative relapse rate at week 52 after randomization, defined as the proportion of participants experiencing at least one protocol-defined IgG4-RD relapse event.
Secondary objectives include evaluation of the effect of lenalidomide on time to first relapse, maintenance of remission, disease activity changes, quality of life, and safety outcomes. Secondary endpoints include time to first IgG4-RD relapse, changes in IgG4-RD Responder Index scores, health-related quality of life assessments, and the incidence of adverse events, serious adverse events, and treatment discontinuations.
Exploratory objectives include characterization of immunological and biological changes associated with lenalidomide treatment during the remission maintenance phase. Exploratory endpoints include changes from baseline in serum IgG4, IgG, IgE, complement components (C3 and C4), inflammatory markers, peripheral blood immune cell subsets, transcriptomic profiles, and gut microbiota characteristics.
Safety monitoring will focus on known and potential risks associated with lenalidomide treatment, including hematologic toxicity, thromboembolic events, infections, skin reactions, hepatic and renal abnormalities, and reproductive safety risks. Adverse events and serious adverse events will be continuously monitored throughout the study. An independent data monitoring committee will periodically review accumulated safety data to ensure participant safety and evaluate the overall benefit-risk profile of the intervention.
This study aims to determine whether lenalidomide can serve as an effective and safe glucocorticoid-sparing maintenance therapy for patients with IgG4-RD in sustained clinical remission, with the potential to reduce disease recurrence, prolong remission duration, and minimize long-term glucocorticoid exposure.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 3
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Yufei Guo, MD
- Número de teléfono: +86 010-55499314
- Correo electrónico: dt_guoyf0412@outlook.com
Copia de seguridad de contactos de estudio
- Nombre: Yiwen Wang, MD
- Número de teléfono: +86 010-55499314
- Correo electrónico: yiwenvera@163.com
Ubicaciones de estudio
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Beijing Municipality
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Beijing, Beijing Municipality, Porcelana, 100853
- The First Medical Center of Chinese PLA General Hospital
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Contacto:
- Yufei Guo, MD
- Número de teléfono: +86 010-55499314
- Correo electrónico: dt_guoyf0412@outlook.com
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Contacto:
- Yiwen Wang, MD
- Número de teléfono: +86 010-55499314
- Correo electrónico: yiwenvera@163.com
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Investigador principal:
- Jian Zhu, MD, Ph.D
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Sub-Investigador:
- Yiwen Wang, MD
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Hainan
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Sanya, Hainan, Porcelana, 572013
- Hainan Hospital of Chinese PLA General Hospital
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Contacto:
- Chao Xue, MM
- Número de teléfono: +86 15692537568
- Correo electrónico: xuechao301hn@163.com
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Sub-Investigador:
- Xiaofei Liu, MM
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Sub-Investigador:
- Chao Xue, MM
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Hubei
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Wuhan, Hubei, Porcelana, 430070
- General Hospital of Central Theater Command
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Contacto:
- Jiali Yu, MM
- Número de teléfono: +86 15527777152
- Correo electrónico: jiali_jlyu@126.com
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Sub-Investigador:
- Lifeng Chen, MD
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Sub-Investigador:
- Jiali Yu, MM
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Lenalidomide Arm
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.
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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.
Otros nombres:
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Comparador de placebos: Placebo Arm
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.
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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.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Cumulative relapse rate of IgG4-related disease at Week 52
Periodo de tiempo: From randomization to Week 52
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The proportion of participants experiencing at least one protocol-defined IgG4-related disease relapse from randomization to Week 52.
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From randomization to Week 52
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Incidence of adverse events and serious adverse events
Periodo de tiempo: From first dose of study intervention to Week 52
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Incidence of adverse events, serious adverse events, adverse events leading to treatment interruption or discontinuation, and adverse events of special interest during the study period.
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From first dose of study intervention to Week 52
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Time to first IgG4-related disease relapse
Periodo de tiempo: From randomization to Week 52
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Time from randomization to the first occurrence of protocol-defined IgG4-related disease relapse.
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From randomization to Week 52
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Changes in immunological biomarkers
Periodo de tiempo: Baseline, Week 4, Week 8, Week 12, Week 26, Week 39, and Week 52
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Changes from baseline in serum IgG4, IgG, IgE, complement components, inflammatory markers, peripheral blood immune cell subsets, transcriptomic profiles, and gut microbiota characteristics.
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Baseline, Week 4, Week 8, Week 12, Week 26, Week 39, and Week 52
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Jian Zhu, MD, PhD, The First Medical Center of Chinese PLA General Hospital
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
- 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.
- 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.
- 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.
- 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.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades autoinmunes
- Enfermedades del sistema inmunológico
- Enfermedad relacionada con inmunoglobulina G4
- Químicos orgánicos
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Compuestos heterocíclicos, 2 anillos
- Compuestos heterocíclicos, anillo fusionado
- Ácidos carboxílicos
- Piperidinas
- Ftalimidas
- Ácidos ftálicos
- Ácidos, carbocíclicos
- Piperidonas
- Isoindoles
- Lenalidomida
- vicilin protein, plant
Otros números de identificación del estudio
- 301-Rheuma-0511
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Marco de tiempo para compartir IPD
Criterios de acceso compartido de IPD
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
- CIF
Información sobre medicamentos y dispositivos, documentos del estudio
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