Treatment Strategies in IgG4-RD Patients With Re-elevation of Serum IgG4 Level During Maintenance Remission Period

NCT05974683 | Unknown

• 1 other identifier: IgG4 re-elevation treatment
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

This study has been designed as a 52-week, randomized double blind placebo controlled multicenter clinical trial. The study aims to compare the efficacy and safety of two treatment strategies in IgG4-RD patients with re-elevation of serum IgG4 level during maintenance remission period: basic maintenance treatment group (continue use of basic maintenance treatment of IgG4-RD) and enhanced treatment group (use low dose mycophenolate mofetil as an add-on therapy of basic maintenance treatment of IgG4-RD).

Conditions

Autoimmune Diseases

Keywords

Immunoglobulin G4-Related Disease; Drug therapy; Relapse

Outcome Measures

Primary Outcomes (1)

• The difference of relapse rate of IgG4-RD between two groups in week 52.

  The primary endpoint is the difference of relapse rate between two groups at 52 weeks. The definition of relapse: elevation of IgG4-RD Responder Index ≥ 2 points; new organ involvement or recurrence, with or without elevation of serum IgG4 levels.

  52 weeks

Secondary Outcomes (11)

• The difference of relapse rate of IgG4-RD between two groups in the week 12.

  12 weeks

• The difference of relapse rate of IgG4-RD between two groups in the week 24

  24 weeks

• The difference of relapse rate of IgG4-RD between two groups in the week 36.

  36 weeks

• The time and duration of relapse

  52 weeks

• The changes of IgG4-RD Responder Index at week 52

  52 weeks

Study Arms (2)

Basic Maintenance Treatment

PLACEBO COMPARATOR

Continue use of current basic maintenance treatment of IgG4-RD plus placebo, Follow-up intervals: week 4, week 12, week 24, week 36, week 52

Drug: placebo

Enhancement Treatment

ACTIVE COMPARATOR

Use low dose mycophenolate mofetil (0.5g per day) as an add-on therapy of current basic maintenance treatment of IgG4-RD, Follow-up intervals: week 4, week 12, week 24, week 36, week 52

Drug: mycophenolate mofetil

Interventions

placebo DRUG

Continue use of current basic maintenance treatment of IgG4-RD plus placebo, Follow-up intervals: week 4, week 12, week 24, week 36, week 52

Basic Maintenance Treatment

mycophenolate mofetil DRUG

Use low dose mycophenolate mofetil (0.5g per day) as an add-on therapy of current basic maintenance treatment of IgG4-RD, Follow-up intervals: week 4, week 12, week 24, week 36, week 52

Enhancement Treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Fulfillment of the 2019 American College of Rheumatology/European League against Rheumatology (ACR/EULAR) IgG4-related disease classification criteria or the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD.
• \. Age between 18 and 70 years.
• \. Elevation of baseline serum IgG4 level (\>1400mg/L).
• \. Major organ involvement, including but not limited to autoimmune pancreatitis, retroperitoneal fibrosis, sclerosing cholangitis, IgG4-related Castleman disease, and involvement of the lungs, kidney, nasal sinus, and central nervous system.
• \. Re-elevation of serum IgG4 level to ≥30% of baseline serum IgG4 level during maintenance remission period, with no evidence of relapse.
• \. Written informed consent signed.
• \. Agreed to take highly effective contraceptive procedures from signing of informed consent till 6 months after the end of last visit.

You may not qualify if:

• \. Patients with an IgG4-RD Responder Index ≥ 2 points of any organ system.
• \. IgG4-RD patients without major organ involvement.
• \. Patients with severe or active infections, including but not limited to HIV, HCV, HBV, TB.
• \. Patients with malignancies or a history of malignancies within 5 years, except:
• Patients with adenocarcinoma in situ (AIS) of the cervix who have received curative treatment for at least 12 months before screening.
• Patients with cutaneous basal or squamous cell carcinoma who have received curative treatment.
• Patients with prostate cancer, who have received radical prostatectomy or definitive radiotherapy for over 3 years, with no sign of relapse or ongoing treatment
• \. Patients with immunodeficiency diseases.
• \. Patients with severe cardiovascular, respiratory, endocrine, gastrointestinal, hematological, neuropsychological, or constitutional comorbidities; or at risk of unacceptable complications, or having confounding factors in safety and explanation of results according to the evaluations from investigators.
• \. Patients with other rheumatic diseases, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, sarcoidosis; or other mimickers of IgG4-RD, including but not limited to Rosai-Dorfman disease, Castleman disease.
• \. Participating in any other clinical trials with drug interventions.
• \. A history of alcohol or drug abuse, possibly harming patient's safety, compliance, or evaluation of study's safety or other necessary aspects according to the evaluations from investigators.
• \. Women during pregnancy, lactation, or planning of pregnancy within 6 months of the last visit of the study.
• \. Meeting any of the following blood test finding on screening:
• Hemoglobin level \< 7.5g/dL.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Beijing Friendship Hospital: collaborator
• Tongji Hospital: collaborator

Study Sites (1)

Peking Union Medical College Hospital

Beijing, China

Location

Related Publications (8)

• Zhang W, Stone JH. Management of IgG4-related disease. Lancet Rheumatol. 2019 Sep;1(1):e55-e65. doi: 10.1016/S2665-9913(19)30017-7. Epub 2019 Aug 28.

  PMID: 38229361 BACKGROUND

• Wallace ZS, Naden RP, Chari S, Choi HK, Della-Torre E, Dicaire JF, Hart PA, Inoue D, Kawano M, Khosroshahi A, Lanzillotta M, Okazaki K, Perugino CA, Sharma A, Saeki T, Schleinitz N, Takahashi N, Umehara H, Zen Y, Stone JH; Members of the ACR/EULAR IgG4-RD Classification Criteria Working Group. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Ann Rheum Dis. 2020 Jan;79(1):77-87. doi: 10.1136/annrheumdis-2019-216561. Epub 2019 Dec 3.

  PMID: 31796497 BACKGROUND

• Lin W, Lu S, Chen H, Wu Q, Fei Y, Li M, Zhang X, Tian X, Zheng W, Leng X, Xu D, Wang Q, Shen M, Wang L, Li J, Wu D, Zhao L, Wu C, Yang Y, Peng L, Zhou J, Wang Y, Sha Y, Huang X, Jiao Y, Zeng X, Shi Q, Li P, Zhang S, Hu C, Deng C, Li Y, Zhang S, Liu J, Su J, Hou Y, Jiang Y, You X, Zhang H, Yan L, Zhang W, Zhao Y, Zeng X, Zhang F, Lipsky PE. Clinical characteristics of immunoglobulin G4-related disease: a prospective study of 118 Chinese patients. Rheumatology (Oxford). 2015 Nov;54(11):1982-90. doi: 10.1093/rheumatology/kev203. Epub 2015 Jun 22.

  PMID: 26106212 BACKGROUND

• Umehara H, Okazaki K, Kawa S, Takahashi H, Goto H, Matsui S, Ishizaka N, Akamizu T, Sato Y, Kawano M; Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare (MHLW) Japan.. The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD. Mod Rheumatol. 2021 May;31(3):529-533. doi: 10.1080/14397595.2020.1859710. Epub 2021 Jan 28.

  PMID: 33274670 BACKGROUND

• Khosroshahi A, Wallace ZS, Crowe JL, Akamizu T, Azumi A, Carruthers MN, Chari ST, Della-Torre E, Frulloni L, Goto H, Hart PA, Kamisawa T, Kawa S, Kawano M, Kim MH, Kodama Y, Kubota K, Lerch MM, Lohr M, Masaki Y, Matsui S, Mimori T, Nakamura S, Nakazawa T, Ohara H, Okazaki K, Ryu JH, Saeki T, Schleinitz N, Shimatsu A, Shimosegawa T, Takahashi H, Takahira M, Tanaka A, Topazian M, Umehara H, Webster GJ, Witzig TE, Yamamoto M, Zhang W, Chiba T, Stone JH; Second International Symposium on IgG4-Related Disease. International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease. Arthritis Rheumatol. 2015 Jul;67(7):1688-99. doi: 10.1002/art.39132. No abstract available.

  PMID: 25809420 BACKGROUND

• Yunyun F, Yu P, Panpan Z, Xia Z, Linyi P, Jiaxin Z, Li Z, Shangzhu Z, Jinjing L, Di W, Yamin L, Xiaowei L, Huadan X, Xuan Z, Xiaofeng Z, Fengchun Z, Yan Z, Wen Z. Efficacy and safety of low dose Mycophenolate mofetil treatment for immunoglobulin G4-related disease: a randomized clinical trial. Rheumatology (Oxford). 2019 Jan 1;58(1):52-60. doi: 10.1093/rheumatology/key227.

  PMID: 30124952 BACKGROUND

• Peng Y, Li JQ, Zhang PP, Zhang X, Peng LY, Chen H, Zhou JX, Zhang SZ, Yang HX, Liu JJ, Guo HF, Li J, Zhang X, Zhao Y, Zeng XF, Zhang FC, Fei YY, Zhang W. Clinical outcomes and predictive relapse factors of IgG4-related disease following treatment: a long-term cohort study. J Intern Med. 2019 Nov;286(5):542-552. doi: 10.1111/joim.12942. Epub 2019 Jun 17.

  PMID: 31121062 BACKGROUND

• Liu Z, Peng Y, Li J, Lu H, Peng L, Zhou J, Zhou S, Huang C, Wang M, Zhu L, Chen H, Wang L, Fei Y, Zhao Y, Zeng X, Zhang W. Prediction of new organ onset in recurrent immunoglobulin G4-related disease during 10 years of follow-up. J Intern Med. 2022 Jul;292(1):91-102. doi: 10.1111/joim.13477. Epub 2022 Apr 13.

  PMID: 35419810 BACKGROUND

MeSH Terms

Conditions

Autoimmune Diseases; Immunoglobulin G4-Related Disease; Recurrence

Interventions

Mycophenolic Acid

Condition Hierarchy (Ancestors)

Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Officials

• Wen Zhang, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiaxin Zhou, MD

CONTACT

86-10-69155647; pumczhou@sina.com

Linyi Peng, MD

CONTACT

86-10-69155647; pumczhou@sina.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 5, 2023
• First Posted: August 3, 2023
• Study Start: August 1, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: August 3, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)